[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"acute-lymphoblastic-leukemia-in-relapse\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:acute-lymphoblastic-leukemia-in-relapse":26},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,18,0,[8,42,85,111,132,152,173,191,210,240,278,301,332,366,394,419,442,465],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":4,"maxAge":17,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":30,"lastUpdatePostDateStruct":31,"startDateStruct":34,"completionDateStruct":36,"leadSponsor":38,"locationsCount":41},"100430143","phase-1-study-of-cd19-allogeneic-memory-t-cell-therapy-for-relapsedrefractory-cd19-leukemia-100430143",false,"NCT04881240","Study of CD19 Allogeneic Memory T-cell Therapy for Relapsed\u002FRefractory CD19+ Leukemia","A Phase I Study Evaluating Allogeneic Memory T Cells Engineered to Express Chimeric Antigen Receptors Specific for CD19 for the Treatment of Pediatric and Young Adult Patients ≤ 21 Years of Age With Relapsed or Refractory CD19-Positive Leukemia","Inclusion Criteria Eligibility Criteria for Donors: Apheresis and Manufacturing\n\n* Age ≥ 18 years old\n* At least single haplotype matched (≥ 3\u002F6) family member\n* HIV negative\n* For females of child bearing age: Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment AND Not lactating with intent to breastfeed\n* Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance\n\nFor Cohort A only, identified recipient with relapsed and\u002For refractory CD19-positive leukemia\n\nFor Cohort B only, iIdentified recipient with relapsed and\u002For refractory CD19-positive leukemia who is not suitable to receive autologous CD19-CAR T-cell therapy as defined by the following:\n\n* Relapsed and\u002For refractory disease despite prior treatment with autologous CD19- CAR T-cell therapy\n* History of prior autologous leukapheresis failure\n* History of prior autologous CAR T-cell manufacturing failure\n* Unable to undergo autologous leukapheresis in the opinion of the study PI(s): examples may include - patient small size\u002Flow weight, inadequate T-cell counts, rapidly progressive leukemia, clinical status not amenable to apheresis\n\nEligibility Criteria for Patients: Treatment\n\n* Age ≤ 21 years old\n* Relapsed and\u002For refractory CD19-positive leukemia\\*:\n\n  * Refractory disease (defined as any of the following):\n\n    * Primary refractory disease despite at least 2 cycles of an intensive chemotherapy regimen designed to induce remission\n    * Refractory disease despite salvage therapy\n  * Relapsed disease (defined as any of the following):\n\n    * 2nd or greater relapse\n    * Any relapse after allogeneic hematopoietic cell transplantation (HCT)\n    * 1st relapse if patient requires an allogeneic HCT as part of standard of care relapse therapy, but is found to be ineligible and\u002For unsuitable for HCT\n\nCD19-positivity confirmed within 2 months and after receipt of any CD19-directed therapy\n\n* Patient cohorts:\n\n  * Cohort A: patient has previously received a HCT from the selected CAR T-cell donor\n  * Cohort B - patient has NOT previously received a HCT from the selected CAR T-cell donor.\n* For Cohort B only, not suitable to receive autologous CD19-CAR T-cell therapy as defined above in Criteria: Eligibility Criteria for Donors: Apheresis and Manufacturing\n* Detectable medullary CD19-positive leukemia\n* Estimated life expectancy of ≥ 8 weeks\n* Karnofsky or Lansky performance score ≥ 50\n* No CNS-3 disease or any level of detectable leukemia in CNS with associated neurologic symptoms\n* If history of allogeneic HCT (regardless of donor type), prior to planned CAR T-cell infusion, must meet the following criteria:\n\n  * ≥ 3 months from HCT\n  * have recovered from prior HCT therapy\n  * have no evidence of active GVHD within prior 2 months\n  * have not received a donor lymphocyte infusion (DLI) within the 28 days prior to planned CAR T-cell infusion\n* Adequate cardiac function: left ventricular ejection fraction ≥ 40% or shortening fraction ≥ 25% (function may be supported by pharmacologic therapy)\n* EKG without evidence of clinically significant arrhythmia\n* Adequate renal function: creatinine clearance or radioisotope GFR 50 ml\u002Fmin\u002F1.73m2 (GFR 40 ml\u002Fmin\u002F1.73m2 if \\\u003C 2 years of age)\n* Adequate pulmonary function: forced vital capacity (FVC) ≥ 50% of predicted value; or pulse oximetry ≥ 92% on room air if patient is unable to perform pulmonary function testing\n* Total bilirubin ≤ 3 times the upper limit of normal for age, except in subjects with Gilbert's syndrome\n* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 times the upper limit of normal for age\n* No history of HIV infection\n* No evidence of severe, uncontrolled bacterial, viral or fungal infection\n* Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy\n* For females of child bearing age:\n\n  * Not pregnant with negative serum or urine pregnancy test ≤ 7 days prior to enrollment AND Not lactating with intent to breastfeed\n* If sexually active, agreement to use birth control until 6 months after CAR T-cell infusion\n* No history of hypersensitivity reactions to murine protein-containing products\n* Not receiving systemic steroids therapy exceeding the equivalent of 0.5 mg\u002Fkg\u002Fday of methylprednisolone ≤ 7 days prior to CAR T-cell infusion\n* Not receiving systemic therapy ≤ 14 days prior to CAR T-cell infusion, which will interfere with the activity of the CAR T-cell product in vivo (in the opinion of the study PI(s))\n* Not receiving intrathecal chemotherapy ≤ 7 days prior to CAR T-cell infusion\n\nExclusion Criteria:\n\nNA","ALL","21 Years",{"count":19,"type":20},60,"ESTIMATED","INTERVENTIONAL",[23],"PHASE1","This is a Phase I clinical study evaluating the safety and maximum tolerated dose of a novel CAR T-cell product: allogeneic memory (CD45RA- negative) T-cells expressing a CD19-specific CAR 41BBz (CD19-CAR.CD45RA- negative T-cells) for the treatment of patients ≤ 21 years old with relapsed and\u002F or refractory CD19-positive leukemia.\n\nPrimary Objective\n\nTo determine the maximum tolerated dose (MTD) and characterize the safety profile and dose-limiting toxicities (DLTs) of treatment with allogeneic CD19-CAR.CD45RA-negative T-cells in pediatric, adolescent and young adult patients ≤ 21 years of age, with relapsed and\u002For refractory CD19-positive leukemia.\n\nSecondary Objectives\n\n* To evaluate the anti-leukemic activity of allogeneic CD19-CAR.CD45RA-negative T-cells.\n* To determine rates and severity of graft-versus-host-disease (GVHD) after treatment with allogeneic CD19-CAR.CD45RA-negative T-cells.\n\nExploratory Objectives\n\n* To study the expansion, persistence and phenotype of allogeneic CD19-CAR.CD45RA-negative T-cells.\n* To characterize the cytokine profile in the peripheral blood and CSF after treatment with allogeneic CD19-CAR.CD45RA-negative T-cells.\n* To assess whether allogeneic CD19-CAR.CD45RA-negative T-cells acquire functional versus exhaustion-associated epigenetic programs.\n* To determine immune reconstitution post treatment, and the clonal structure and endogenous repertoire of allogeneic CD19-CAR.CD45RA-negative T-cells and relate inferred specificity to CAR response profiles.\n* To characterize incidence and mechanisms of relapse post-therapy with allogeneic CD19-CAR.CD45RA-negative T-cells.",[26,27,28],"Acute Lymphoblastic Leukemia, in Relapse","Acute Lymphoblastic Leukemia, Refractory","Pediatric ALL","RECRUITING","2026-05-20",{"date":32,"type":33},"2026-05-26","ACTUAL",{"date":35,"type":33},"2024-02-14",{"date":37,"type":20},"2028-07-01",{"name":39,"class":40},"St. Jude Children's Research Hospital","OTHER",1,{"id":43,"slug":44,"hasResults":11,"nctId":45,"briefTitle":46,"officialTitle":47,"acronym":4,"eligibilityCriteria":48,"healthyVolunteers":11,"sex":16,"minAge":49,"maxAge":50,"enrollmentInfo":51,"targetDuration":4,"studyType":21,"phases":53,"briefSummary":54,"conditions":55,"keywords":66,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":75,"lastUpdatePostDateStruct":76,"startDateStruct":78,"completionDateStruct":80,"leadSponsor":82,"locationsCount":84},"100461746","phase-1-venetoclax-basket-trial-for-high-risk-hematologic-malignancies-100461746","NCT05292664","Venetoclax Basket Trial for High Risk Hematologic Malignancies","A Phase I Study of Venetoclax in Combination With Cytotoxic Chemotherapy, Including Calaspargase Pegol, for Children, Adolescents and Young Adults With High-Risk Hematologic Malignancies","Inclusion Criteria\n\nCohort A Inclusion Criteria:\n\n* MDS, AML arising from MDS (MDS\u002FAML), therapy related myeloid neoplasm (tMDS\u002FAML) meeting at least one of the following criteria:\n\n  * MDS with excess blasts (\\>10%)\n  * MDS with blasts \\\u003C10% with high-risk features\n  * MDS refractory to initial treatment\n  * Relapsed MDS\n  * MDS\u002FAML: May be newly diagnosed or relapsed\u002Frefractory disease.\n  * Therapy related myeloid neoplasm (tMDS\u002FAML): May be initial or relapsed\u002Frefractory disease.\n\n    * Note: MDS or MDS\u002FAML may be derived from a germline predisposition to myeloid malignancy as long as that condition does not confer increased toxicity to treatment.\n* Age ≤ 40 years of age, except the following subjects that must be \\\u003C18 years to enroll\n\n  * Subjects with MDS\u002FAML that have not received prior therapy\n  * Subjects enrolled onto Dose level -2.\n* Lansky\u002FKarnofsky performance status ≥ 50%\n* Participants must have fully recovered from the acute toxic effects of all and meet all of the following criteria:\n\n  * Myelosuppressive chemotherapy: 14 days, or 5 half-lifes (whichever is shorter) must have elapsed since the completion of myelosuppressive therapy. Individuals may have received any of the following medications without a \"wash-out\" period\n\n    * Standard maintenance therapy: dexamethasone\u002Fprednisone, vincristine, 6MP, low dose methotrexate)\n    * Hydroxyurea\n    * Intrathecal chemotherapy with methotrexate, hydrocortisone and\u002For cytarabine.\n  * Radiation therapy (XRT):\n\n    * Total Body Irradiation (TBI) or cranial radiation therapy: Must have been completed more than 90 days prior to study entry\n    * XRT for chloroma does not require a washout period.\n    * Palliative XRT does not require a washout\n  * Small molecule inhibitors (BCR-ABL or FLT3 inhibitors, for example): 7 days, or 5 half-lifes, whichever is shorter) must have elapsed since the completion of therapy. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.\n  * Immunotherapy: At least 30 days after the administration of any type of immunotherapy, including, but not limited to, tumor vaccines, chimeric antigen receptor (CAR) therapy, other immune effector cell therapy and checkpoint inhibitors.\n  * Monoclonal antibodies: At least 3 half-lives of the antibody\n  * Prior hematopoietic stem cell transplant (HSCT):\n\n    * Allogeneic HSCT \\> 90 days of study entry\n    * No evidence of graft-versus-host-disease (GVHD)\n  * Adequate organ function, as defined by\n\n    * Serum alanine aminotransferase (ALT) ≤5X upper limit of normal (ULN)\n    * Direct bilirubin ≤ 3X\n    * Ejection fraction ≥ 50% or shortening fraction of ≥ 24% on screening echocardiogram.\n  * Female participants of childbearing potential must have a negative urine or serum HCG prior to study entry and at the start of therapy. All females of childbearing potential must refrain from breastfeeding during study participation, and all male and females of childbearing potential must agree to use an effective form of contraception (abstinence, hormonal, or barrier) prior to study entry, for duration of participation, and for a minimum of 30 days following the last dose of treatment.\n\nCohort B Inclusion Criteria\n\n* MDS, MDS\u002FAML, therapy related myeloid neoplasm (tMDS\u002FAML) that is derived from the following germline disorders:\n\n  * Dyskeratosis Congenita or associated telomeropathies\n  * Fanconi Anemia\n  * Nijmegen Breakage\n  * Other related disorders with high risk of toxicity may be eligible for this cohort after discussion with the Sponsor-Investigator.\n* And meets at least one the following disease characteristics:\n\n  * MDS with excess blasts (\\>10%)\n  * MDS with blasts \\\u003C10% with high-risk features\n  * MDS refractory to initial treatment\n  * Relapsed MDS\n  * MDS\u002FAML: May be newly diagnosed or relapsed\u002Frefractory disease.\n  * Therapy related myeloid neoplasm (tMDS\u002FAML): May be initial or relapsed\u002Frefractory disease.\n* Age ≤ 40 years of age\n* Lansky\u002FKarnofsky performance status ≥ 50%\n* Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and meet all of the following criteria:\n\n  * Myelosuppressive chemotherapy: 14 days, or 5 half-lifes (which ever is shorter) must have elapsed since the completion of myelosuppressive therapy. Individuals may have received any of the following medications without a \"wash-out\" period\n\n    * Standard maintenance therapy: dexamethasone\u002Fprednisone, vincristine, 6MP, low dose methotrexate\n    * Hydroxyurea\n    * Intrathecal chemotherapy with methotrexate, hydrocortisone and\u002For cytarabine.\n  * Radiation therapy (XRT):\n\n    * Total Body Irradiation (TBI) or cranial radiation therapy: Must have been completed more than 90 days prior to study entry\n    * XRT for chloroma does not require a washout period.\n    * Palliative XRT does not require a washout\n  * Small molecule inhibitors (BCR-ABL or FLT3 inhibitors, for example): 7 days, or 5 half-lifes, whichever is shorter) must have elapsed since the completion of therapy. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.\n  * Immunotherapy: At least 30 days after the administration of any type of immunotherapy, including, but not limited to, tumor vaccines, chimeric antigen receptor (CAR) therapy, other immune effector cell therapy and checkpoint inhibitors.\n  * Monoclonal antibodies: At least 3 half-lives of the antibody\n  * Prior hematopoietic stem cell transplant (HSCT): Must meet all of the following conditions:\n\n    * Allogeneic HSCT \\> 90 days of study entry\n    * No evidence of graft-versus-host-disease (GVHD)\n* Adequate organ function, as defined by\n\n  * Serum alanine aminotransferase (ALT) ≤5X upper limit of normal (ULN)\n  * Direct bilirubin ≤ 3X upper limit of normal for age and institution.\n* Ejection fraction ≥ 50% or shortening fraction of ≥ 24% on screening echocardiogram.\n* Because of the teratogenic effects of venetoclax on developing fetuses, female participants of childbearing potential must have a negative urine or serum HCG prior to study entry and at the start of therapy. All females of childbearing potential must refrain from breastfeeding during study participation, and all male and females of childbearing potential must agree to use an effective form of contraception (abstinence, hormonal, or barrier) prior to study entry, for duration of participation, and for a minimum of 30 days following the last dose of treatment.\n\nCohort C Inclusion Criteria\n\n* Part I: B-cell or T-cell acute lymphoblastic leukemia (ALL), mixed phenotype acute lymphoblastic leukemia (MPAL) or lymphoblastic lymphoma (LBL) in first or greater relapse or refractory to at least 1 prior remission induction attempt.\n\n  * For ALL\u002FMPAL: Bone marrow involvement ≥ 5% by aspirate morphology or ≥ 1% assessable by flow cytometry or validated molecular minimal residual disease (MRD) testing\n  * For LBL: Radiographically detectable mass or lymph node involvement\n* Part II: Histologically confirmed diagnosis of one of the following:\n\n  * T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL) in first or greater relapse or refractory to at least 1 prior remission induction attempt.\n\n    * For T-ALL: Bone marrow involvement ≥ 5% by aspirate morphology or ≥ 1% assessable by morphology, flow cytometry or validated MRD testing\n    * For T-LBL (biopsy proven at current or prior relapse): Radiographically detectable mass or lymph node involvement OR\n  * Relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) with bone marrow involvement ≥1% (assessable by morphology, flow cytometry or validated MRD testing) and at least one of the following characteristics:\n\n    * First relapse with adverse biologic determinants as described below:\n\n      * KMT2A rearrangement\n      * Low hypodiploidy, defined as ≤ 40 chromosomes\n      * t(17;19)\n      * IKZF1 deletion (without targetable ABL1 fusion)\n      * Ph-like ALL (without targetable ABL1 fusion)\n      * Other biologic determinants with adverse prognosis in discussion with the Sponsor-Investigator\n    * Early first bone marrow relapse occurring \\\u003C36 months from initial diagnosis\n    * Primary refractory ALL that has failed 1 prior induction attempt\n* Age: ≥ 1 and ≤ 21 years of age\n* Lansky\u002FKarnofsky performance status ≥ 50%\n* Participants must have fully recovered from the acute toxic effects of all prior and meet all of the following criteria:\n\n  * Myelosuppressive chemotherapy: 14 days, or 5 half-lives, whichever is shorter, must have elapsed since the completion of myelosuppressive therapy. Individuals may have received any of the following medications without a \"wash-out\" period:\n\n    * Standard maintenance therapy: dexamethasone\u002Fprednisone, vincristine, 6MP, low dose methotrexate\n    * Hydroxyurea\n    * Intrathecal chemotherapy with methotrexate, hydrocortisone and\u002For cytarabine.\n  * Radiation therapy (XRT):\n\n    * Total Body Irradiation (TBI) or cranial radiation therapy: Must have been completed more than 90 days prior to study entry\n    * XRT for chloroma does not require a washout period.\n    * Palliative XRT does not require a washout\n  * Small molecule inhibitors (BCR-ABL or FLT3 inhibitors, for example): 7 days, or 5 half-lifes, whichever is shorter) must have elapsed since the completion of therapy. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.\n  * Immunotherapy: At least 30 days after the administration of any type of immunotherapy, including, but not limited to, tumor vaccines, chimeric antigen receptor (CAR) therapy, other immune effector cell therapy and checkpoint inhibitors.\n  * Monoclonal antibodies: At least 3 half-lives of the antibody after the last dose of a monoclonal antibody\n  * Prior hematopoietic stem cell transplant (HSCT): Patients who have received HSCT are eligible, but must meet all of the following conditions:\n\n    * Allogeneic HSCT \\> 90 days of study entry\n    * No evidence of graft-versus-host-disease (GVHD)\n* Adequate organ function, as defined by the following laboratory values:\n\n  * Serum alanine aminotransferase (ALT) ≤5X upper limit of normal (ULN), unless deemed secondary to leukemic involvement in discussion with site PI.)\n  * Direct bilirubin ≤ 3X upper limit of normal for age and institution.\n  * Serum amylase ≤ 3X institutional ULN .\n* Cardiac function as defined as below:\n\n  * Ejection fraction ≥ 50% or shortening fraction of ≥ 24% on screening echocardiogram.\n  * Maximum prior cumulative doxorubicin dose ≤ 360 mg\u002Fm2 or equivalent\n* Because of the teratogenic effects of venetoclax on developing fetuses, female participants of childbearing potential must have a negative urine or serum HCG prior to study entry and at the start of therapy. All females of childbearing potential must refrain from breastfeeding during study participation, and all male and females of childbearing potential must agree to use an effective non-hormonal form of contraception (abstinence, barrier) prior to study entry, for duration of participation, and for a minimum of 3 months following the last dose of treatment (as calaspargase pegol can render hormonal contraceptives ineffective).\n\nExclusion Criteria\n\nCohort A Exclusion Criteria\n\n* Use of strong or moderate CYP3A inhibitors\u002Finducers within 3 days of study entry\n* Individuals who have had a stem cell transplant and are still receiving treatment for GVHD or GVHD prophylaxis, or who have evidence of acute GVHD\n* Individuals with known active hepatitis; baseline testing not required.\n* Patients with systemic infection that is exhibiting ongoing signs\u002Fsymptoms related to the infection without improvement despite appropriate antibiotics or other treatment.\n* Patients known to have human immunodeficiency virus (HIV) infection; baseline testing for HIV is not required.\n* Pregnant or nursing women are excluded.\n* Individuals with significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.\n\nCohort B Exclusion Criteria\n\n* Use of strong or moderate CYP3A inhibitors\u002Finducers within 3 days of study entry\n* Individuals who have had a stem cell transplant and are still receiving treatment for GVHD or GVHD prophylaxis, or who have evidence of acute GVHD\n* Individuals with known active hepatitis; baseline testing not required.\n* Patients with systemic infection that is exhibiting ongoing signs\u002Fsymptoms related to the infection without improvement despite appropriate antibiotics or other treatment.\n* Patients known to have human immunodeficiency virus (HIV) infection; baseline testing for HIV is not required.\n* Pregnant or nursing women are excluded.\n* Individuals with significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.\n\nCohort C Exclusion Criteria\n\n* Use of strong or moderate CYP3A inhibitors\u002Finducers within 3 days of study entry\n* Individuals who have had a stem cell transplant and are still receiving treatment for GVHD or GVHD prophylaxis, or who have evidence of acute GVHD, or who are less than 90 days from stem cell infusion\n* Individuals with known active hepatitis; baseline testing not required.\n* Patients with systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs\u002Fsymptoms related to the infection without improvement despite appropriate antibiotics or other treatment.\n* Patients known to have human immunodeficiency virus (HIV) infection; baseline testing for HIV is not required.\n* Pregnant or nursing women are excluded\n* Individuals with significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.\n* Individuals with a history of allergic reactions to any of the agents being used in this trial, with the exception of pegaspargase or calaspargase pegol. Participants with a history of allergy to pegylated formulation of asparasginase are allowed on study but should receive commercial supply of asparaginase Erwinia chrysanthemi (Erwinaze), crisantaspase (Erwinase), or asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze) instead of calaspargase pegol (see Sections 6.2.6 and 6.2.7). Individuals with a history of allergy to Erwinaze, Erwinase or Rylaze are excluded from the study.\n* History of asparaginase-associated pancreatitis.\n* Known, active and propagating deep venous thrombus (DVT).\n* Individuals with isolated CNS or testicular relapse.\n* Presence of surface immunoglobulin by flow cytometry and\u002For known t(8;14), t(2;8), or t(8;22).\n* Individuals with a history of a different malignancy are ineligible except for the following circumstances:\n\n  * Individuals are eligible if they have been disease-free for at least 1 year and are deemed by the investigator to be at low risk for recurrence of that malignancy.\n  * Individuals with the following cancers are eligible if diagnosed and treated within the past year: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.","1 Year","40 Years",{"count":52,"type":20},30,[23],"This trial is evaluating the safety and tolerability of venetoclax with chemotherapy in pediatric and young adult patients with hematologic malignancies, including myelodysplastic syndrome (MDS), acute myeloid leukemia derived from myelodysplastic syndrome (MDS\u002FAML), and acute lymphoblastic leukemia (ALL)\u002Flymphoblastic lymphoma (LBL).\n\nThe names of the study drugs involved in this study are below. Please note this is a list for the study as a whole, participants will receive drugs according to disease cohort.\n\n* Venetoclax\n* Azacitidine\n* Cytarabine\n* Methotrexate\n* Hydrocortisone\n* Leucovorin\n* Dexamethasone\n* Vincristine\n* Doxorubicin\n* Dexrazoxane\n* Calaspargase pegol\n* Hydrocortisone",[56,57,58,59,60,26,61,62,63,64,65],"Myelodysplastic Syndromes, de Novo","Myelodysplastic Syndromes, Secondary","Myelodysplastic Syndromes, Previously Treated","Treatment-Related Acute Myeloid Leukemia","Therapy-Related Myelodysplastic Syndrome","Acute Lymphoblastic Leukemia With Failed Remission","Lymphoblastic Lymphoma, in Relapse","Lymphoblastic Lymphoma, Refractory","Acute Leukemia of Ambiguous Lineage in Relapse","Acute Leukemia of Ambiguous Lineage",[67,68,69,70,71,72,73,74],"Myelodysplastic Syndrome (MDS)","Treatment-related Acute Myelogenous Leukemia","AML arising from MDS","Relapsed or Refractory Acute Lymphoblastic Leukemia","Relapsed or Refractory Acute Lymphoblastic Lymphoma","Relapsed or Refractory MDS","Treatment-related MDS","Relapsed or Refractory Acute leukemia of ambiguous lineage","2026-03-10",{"date":77,"type":33},"2026-03-12",{"date":79,"type":33},"2023-03-29",{"date":81,"type":20},"2030-07-02",{"name":83,"class":40},"Andrew E. Place, MD",5,{"id":86,"slug":87,"hasResults":11,"nctId":88,"briefTitle":89,"officialTitle":90,"acronym":4,"eligibilityCriteria":91,"healthyVolunteers":11,"sex":16,"minAge":49,"maxAge":92,"enrollmentInfo":93,"targetDuration":4,"studyType":21,"phases":95,"briefSummary":97,"conditions":98,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":102,"lastUpdatePostDateStruct":103,"startDateStruct":104,"completionDateStruct":106,"leadSponsor":108,"locationsCount":110},"100540439","phase-1-cd5-chimeric-antigen-receptor-car-t-cells-in-subjects-with-relapsed-or-refractory-t-cell-malignancies-100540439","NCT06316856","CD5 Chimeric Antigen Receptor (CAR) T Cells in Subjects With Relapsed or Refractory T-cell Malignancies","CD5 Chimeric Antigen Receptors (CAR) T Cells in Subjects With Relapsed or Refractory T-Cell Malignancies: a Multi-center, Open-label, Non-randomized, Phase 1\u002F2 Clinical Trial","Inclusion Criteria:\n\nOnly patients who meet all the following criteria can be included:\n\n1. Candidates with relapse or refractory CD5+ T-cell malignancies, who have progressed after treatment with all standard therapies or been intolerant of standard care, have limited prognosis with currently available therapies and have no available curative treatment options (such as stem-cell transplantation (SCT) or chemotherapy);\n2. For subjects who received autologous CD5 CAR T cells, the tumor burden in peripheral blood is less than 20%, and suspending anti-neoplastic treatment for more than 2 weeks;\n3. Aged 1-70 years;\n4. No severe allergy;\n5. Eastern Cooperative Oncology Group (ECOG) performance status 1 score 0 to 2;\n6. Patients are expected to live for at least 60 days;\n7. CD5+ on blasts in bone marrow (BM) or cerebrospinal fluid (CSF) and tumor tissues by flow cytometry and immunohistochemistry, respectively. (Positive rate \\>80% by flow cytometry with less than one log difference in mean fluorescence intensity from normal T cells, or positive rate \\>30% positive by immunohistochemistry);\n8. Provide a signed informed consent before any screening procedure. Subjects who voluntarily participate in the study should have the ability to understand and sign the informed consent form and be willing to follow the study visit schedule and relevant study procedure, as specified in the protocol. Candidates aged 19-70 years need to be sufficiently conscious and able to sign the treatment consent form and voluntary consent form. Children candidates of 8-18 years old need to be sufficiently conscious and able to sign the treatment consent form and voluntary consent form and their legal guardian or patient advocate has also need to sign the treatment consent form and voluntary consent form, respectively. Children candidates of 1-7 can be recruited after the legal guardian or patient advocate has signed the treatment consent form and voluntary consent form;\n9. Have available allogeneic hematopoietic stem cell transplantation donor for the subject who received newly matched donor-derived CD5 CAR T cells, and is willing to perform SCT when CR is achieved.\n\nExclusion Criteria:\n\nPatients with at least one of the following conditions are excluded:\n\n1. Impaired consciousness or intracranial hypertension;\n2. Symptomatic congestive heart failure or severe cardiac arrhythmia;\n3. Manifestations of severe respiratory system failure;\n4. Co-existence with other malignancies;\n5. Disseminated intravascular coagulation;\n6. Serum creatinine and\u002For blood urea nitrogen (BUN) ≥ 1.5-fold upper limit;\n7. Sepsis or other uncontrollable infections;\n8. Uncontrollable diabetes;\n9. Serious mental illness;\n10. Apparent and active intracranial lesions on cranial magnetic resonance imaging (MRI);\n11. Underwent organ transplantation, excepting SCT;\n12. Pregnant females;\n13. Positive test for infectious hepatitis, acquired immune deficiency syndrome (AIDS) or syphilis;\n14. Post-CAR SCT is not feasible in patients who plan to receive newly matched donor-derived CD5 CAR T cells;\n15. Inability to collect peripheral blood mononuclear cells (PBMC) or no frozen PBMC available for CAR T cell manufacturing.","70 Years",{"count":94,"type":20},54,[23,96],"PHASE2","This is a multi-center, open-label, non-randomized, phase 1\u002F2 study of anti-CD5 CAR-T cell therapy in patients with CD5+ relapsed or refractory T-cell malignancies. A bayesian optimal interval (BOIN) 12 design will be used to explore the optimal biological dose (OBD) from starting dose level 1: 1×10\\^6 (±20%) to dose level 2: 2×10\\^6 (±20%) in three cohorts (autologous, previous-transplant-donor or newly matched donor-derived CD5 CAR T cells). If the manufactured cells are not sufficient to meet the preassigned standard dose criteria, patients will be given infusion at a low dose level of 5×10\\^5 (±20%) \u002Fkg. The primary objective is to evaluate the safety and tolerability of CD5 CAR T cell therapy in subjects, determine the OBD and recommend phase 2 dose (RP2D) in phase 1, and evaluate the efficacy of CD5 CAR T cell therapy in phase 2. The primary endpoint is the type and incidence of dose-limiting toxicity (DLT) within 28 days, and the incidence and severity of adverse events (AEs) within 30 days after CD5 CAR T-cell infusion in phase 1, the best overall response (BOR) at 3 months (± 1 week) after CD5 CAR T-cell infusion in phase 2. A total number of 54 subjects will be enrolled.",[99,26,100,101],"T-Cell Acute Lymphocytic Leukemia","Refractory Acute Lymphoblastic Leukemia","T-cell Malignancies","2026-03-06",{"date":75,"type":33},{"date":105,"type":33},"2024-06-18",{"date":107,"type":20},"2026-12-30",{"name":109,"class":40},"Beijing GoBroad Hospital",4,{"id":112,"slug":113,"hasResults":11,"nctId":114,"briefTitle":115,"officialTitle":116,"acronym":4,"eligibilityCriteria":117,"healthyVolunteers":11,"sex":16,"minAge":49,"maxAge":92,"enrollmentInfo":118,"targetDuration":4,"studyType":21,"phases":120,"briefSummary":122,"conditions":123,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":102,"lastUpdatePostDateStruct":126,"startDateStruct":127,"completionDateStruct":129,"leadSponsor":131,"locationsCount":41},"100542455","clinical-trial-of-cd19-and-cd22-car-sequential-therapy-versus-single-cd19-car-bridging-to-hsct-for-rr-b-all-patients-100542455","NCT06343090","Clinical Trial of CD19 and CD22 CAR Sequential Therapy Versus Single CD19 CAR Bridging to HSCT for r\u002Fr B-ALL Patients","Pragmatic Clinical Trial of CD19 and CD22 CAR T-cell Sequential Therapy Versus Single CD19 CAR T-cell Bridging to Transplantation for Patients With Refractory or Relapsed B-cell Acute Lymphoblastic Leukemia","Inclusion Criteria:\n\n* Only patients who meet all the following criteria can be included in the group:\n\n  1. Patients who were diagnosed as primary refractory or relapsed B-ALL. (Criterion-reference: NCCN, version 2.2023); All the patients matched the diagnostic criteria of ALL according to the NCCN guideline (≥20% bone marrow lymphoblasts on hematopathology review of bone marrow aspirate and biopsy materials, which were confirmed by comprehensive flow cytometric immunophenotyping, minimal residual disease analysis and karyotyping of G-banded metaphase chromosomes). Molecular characterization could be obtained via interphase fluorescence in situ hybridization (FISH) testing, reverse transcriptase polymerase chain reaction (RT-PCR) testing, comprehensive testing by next-generation sequencing (NGS) for gene fusions and pathogenic mutations, etc. Determination of the World Health Organization ALL subtypes and cytogenetic and clinical risk groups were also allowed. B-ALL patients who did not achieve a complete remission after previous therapy (including the various treatment response scenarios shown in Table 1), who did not achieve a complete remission after at least two lines of TKI agents (including the various treatment response scenarios shown in Table 1), or who had ≥1 relapses were defined as having refractory or relapsed disease. Patients who were diagnosed as CD19- and CD22-positive high-risk B-ALL with continuous positive minimal residual disease (MRD) for more than three months after last therapy were also eligible. Patients had positive CD19 and CD22 expression on leukemia blasts by FCM (\\>80% CD19 and CD22 positive);\n  2. Age from 1 to 70 years old;\n  3. No serious allergic constitution;\n  4. Eastern Cooperative Oncology Group (ECOG) performance status (Oken et al., 1982) score 0 to 2;\n  5. Have life expectancy of at least 60 days based on investigator's judgement;\n  6. Voluntary informed consent is signed by self-aware patients aged 8-70 years and by legal representatives (guardians) of pediatric patients under 18 years of age.\n\nExclusion Criteria:\n\n* Patients with at least one of the following conditions are excluded:\n\n  1. Intracranial hypertension or unconscious;\n  2. Acute heart failure or severe arrhythmia;\n  3. Acute respiratory failure;\n  4. Other types of malignant tumors;\n  5. Diffuse intravascular coagulation;\n  6. Serum creatinine and\u002For blood urea nitrogen over 1.5 times the normal value;\n  7. Sepsis or other uncontrolled infection;\n  8. Uncontrolled diabetes mellitus;\n  9. Severe psychological disorder;\n  10. Obvious cranial lesions by cranial MRI;\n  11. More than 20 leukemic cells\u002FμL in cerebrospinal fluid;\n  12. More than 30% leukemic cells in the peripheral blood;\n  13. Organ recipients;\n  14. Pregnant or breastfeeding;\n  15. Active, uncontrolled infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or treponema pallidum (TP).",{"count":119,"type":20},353,[121],"NA","This is a multi-center, open-label, non-randomized, two-arm, non-inferior trial. Patients with r\u002Fr B-ALL would be assigned to the CD19 CAR and CD22 CAR T-cell sequential infusion group (Sequential CAR, Arm-1) and the CD19 CAR T-cell infusion bridging to hematopoietic stem cell transplantation group (CAR+HSCT, Arm-2), according their own discretion. Patients would be also allowed to assigned to the CD19 CAR T-cell infusion without consolidation therapies group (Single CAR, additional placebo arm) according their own discretion. The primary objective is to prospectively evaluate and compare the efficacy of CD19 CAR and CD22 CAR T cell sequential infusions and CD19 CAR T-cell infusion bridging to HSCT in the treatment of r\u002Fr B-ALL. The primary endpoint is event-free survival of children and adolescent and young adult (AYA) with r\u002Fr B-ALL a treated with CD19 CAR and CD22 CAR T-cell sequential infusions and CD19 CAR T-cell infusion bridging to HSCT. A total number of 353 subjects will be enrolled.",[124,26,125],"B-cell Acute Lymphoblastic Leukemia","Refractory Acute Lymphoid Leukemia",{"date":75,"type":33},{"date":128,"type":33},"2024-04-12",{"date":130,"type":20},"2043-09-30",{"name":109,"class":40},{"id":133,"slug":134,"hasResults":11,"nctId":135,"briefTitle":136,"officialTitle":137,"acronym":4,"eligibilityCriteria":138,"healthyVolunteers":11,"sex":16,"minAge":49,"maxAge":139,"enrollmentInfo":140,"targetDuration":4,"studyType":21,"phases":142,"briefSummary":143,"conditions":144,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":145,"lastUpdatePostDateStruct":146,"startDateStruct":148,"completionDateStruct":150,"leadSponsor":151,"locationsCount":41},"100541142","phase-1-safety-tolerability-and-pharmacokinetics-of-donor-derived-cd19-car-therapy-bridged-allo-hsct-and-sequential-donor-derived-cd22-car-therapy-for-rr-b-all-a-clinical-trial-100541142","NCT06326008","Safety, Tolerability, and Pharmacokinetics of Donor-derived CD19 CAR Therapy Bridged Allo-HSCT and Sequential Donor-derived CD22 CAR Therapy for r\u002Fr B-ALL: a Clinical Trial","Safety, Tolerability and Pharmacokinetics of Donor-derived CD19 CAR Therapy Bridged Allogeneic Haematopoietic Stem Cell Transplantation and Sequential Donor-derived CD22 CAR Therapy in Refractory or Relapsed B Cell Acute Lymphoblastic Leukemia: a Clinical Trial","Inclusion Criteria:\n\n\\- Patients will be enrolled only if they meet all the inclusion criteria.\n\n1. Patients with relapsed or refractory CD19+\u002FCD22+ (FCM \\>95%) B-cell acute lymphoblastic leukaemia who have progressed despite or are intolerant to all standard therapies, including, but not limited to, immunotherapies such as Blinatumomab (BITE), Tyrosine kinase inhibitors (TKI), CAR T-cell therapy, etc.; Currently available therapies have a limited prognosis and there are no available curative treatment options (e.g., HSCT or chemotherapy);\n2. Peripheral blood tumour burden ≥60% or severe peripheral blood cytopenia, unsuitable\u002Funable to collect autologous lymphocytes;\n3. 1 to 18 years old;\n4. Patient's expected survival time ≥ 60 days;\n5. Physical status: ECOG score 0-2;\n6. Availability of allogeneic donors (HLA-identical or HLA-haploidentical) DSA-negative for collection of peripheral blood mononuclear cells and peripheral blood stem cells;\n7. Sign an informed consent form during the screening period. Pediatric patients under 8\\~18 years of age need to have sufficient awareness to voluntarily sign an informed consent form, and their legal representatives (guardians) also need to voluntarily sign an informed consent form; pediatric patients aged 1\\~7 years can only be recruited after their legal guardians have voluntarily signed an informed consent form.\n\nExclusion Criteria:\n\n* Patients who meet any of the following criteria are not eligible for enrolment.\n\n  1. Patients who have received previous haematopoietic stem cell transplantation (including peripheral blood haematopoietic stem cell transplantation and bone marrow haematopoietic stem cell transplantation);\n  2. Intracranial hypertension or cerebral impaired consciousness;\n  3. Symptomatic heart failure or severe cardiac arrhythmia;\n  4. Symptoms of severe respiratory failure;\n  5. With other types of malignant tumours;\n  6. Diffuse intravascular coagulation;\n  7. Serum creatinine and\u002For urea nitrogen ≥ 1.5 times the normal value;\n  8. Suffering from sepsis or other uncontrollable infections;\n  9. Suffering from uncontrollable diabetes mellitus;\n  10. Severe mental disorders;\n  11. Have significant intracranial lesions on cranial MRI (excluding intracranial masses caused by central nervous system leukaemia);\n  12. Have organ transplant history;\n  13. Female patients (patients of childbearing potential) with positive blood HCG test;\n  14. Hepatitis (including Hepatitis B and Hepatitis C) and positive screening for AIDS and syphilis;\n  15. No allogeneic donor suitable for collection of peripheral blood lymphocytes and haematopoietic stem cells.","18 Years",{"count":141,"type":20},48,[23],"This is an investigator-initiated, single-arm, open-label, non-randomised phase I clinical study. The objective of this trial is to evaluate the safety, tolerability and pharmacokinetics of donor-derived CD19 CAR Therapy bridged Allo-HSCT and sequential donor-derived CD22 CAR Therapy for r\u002Fr B-ALL and to explore the efficacy of this therapy preliminarily. The primary endpoints are incidence and type of dose-limiting toxicity (DLT) within 28 days (i.e., 43 days after donor-derived CD19 CAR T-cell infusion) after donor-derived CD19 CAR T-cell therapy bridged allogeneic haematopoietic stem cell transplantation; total number, incidence and severity of adverse events from donor-derived CD19 CAR T cell infusion back to 30 days after donor-derived CD22 CAR T cell infusion (i.e., within 120 days of donor-derived CD19 CAR T cell infusion). The secondary endpoints are total number, incidence and severity of adverse events from 120 days to 2 years after donor-derived CD19 CAR T-cell infusion; ORR(CR+CRi) on days 45, 90, 120; duration of response(DOR), event-free survival(EFS), overall survival(OS); pharmacokinetics characteristics. The trial plan to enroll 3\\~12 cases in dose escalation phase and 36 cases in dose expansion phase.",[124,26],"2026-03-05",{"date":147,"type":33},"2026-03-09",{"date":149,"type":20},"2026-03-15",{"date":107,"type":20},{"name":109,"class":40},{"id":153,"slug":154,"hasResults":11,"nctId":155,"briefTitle":156,"officialTitle":157,"acronym":4,"eligibilityCriteria":158,"healthyVolunteers":11,"sex":16,"minAge":49,"maxAge":159,"enrollmentInfo":160,"targetDuration":4,"studyType":21,"phases":162,"briefSummary":163,"conditions":164,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":165,"lastUpdatePostDateStruct":166,"startDateStruct":168,"completionDateStruct":170,"leadSponsor":172,"locationsCount":41},"100546005","cik-cell-therapy-for-relapsed-or-refractory-acute-b-lymphoblastic-leukemia-prognostic-impact-on-patients-with-early-car-t-cell-dysfunction-100546005","NCT06389305","CIK Cell Therapy for Relapsed or Refractory Acute B-Lymphoblastic Leukemia: Prognostic Impact on Patients With Early CAR-T Cell Dysfunction","Cytokine-induced Killer(CIK) Cell Therapy and Its Impact on Early Functional Exhaustion of Chimeric Antigen Receptor-T(CAR-T) Cells in Relapsed or Refractory Acute B-Lymphoblastic Leukemia: A Prospective Study","Inclusion Criteria:\n\n* A patient must meet all of the following to be enrolled:\n\n  1. A confirmed diagnosis of refractory or relapsed B-ALL (criteria reference: NCCN, 2024.4), where all patients meet the National Comprehensive Cancer Network(NCCN) guidelines for the diagnosis of acute lymphoblastic leukemia (hematopathological examination of bone marrow aspirate and biopsy tissue showing ≥20% lymphoblasts in the bone marrow, confirmed by comprehensive flow cytometry (FCM) immunotyping, minimal residual disease analysis, and G-banded metaphase chromosome karyotype analysis). Molecular characteristics can be described through methods such as interphase fluorescence in situ hybridization (FISH) testing, reverse transcription polymerase chain reaction (RT-PCR) testing, and next-generation sequencing (NGS) for comprehensive detection of fusion genes and pathogenic mutations. Determination can also be made by the World Health Organization's subtypes of acute lymphoblastic leukemia, as well as cytogenetic and clinical risk groups.\n  2. Loss of CAR-T cell activity within 6 months after previous CAR-T therapy and no relapse.\n  3. Age between 1 and 39 years old.\n  4. No severe allergic constitution.\n  5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.\n  6. Life expectancy, as judged by the investigator, of at least 60 days.\n  7. Patients with self-awareness between 8 and 39 years of age voluntarily sign an informed consent, and the legal representative (guardians) of child patients under 18 years of age voluntarily signs an informed consent.\n\nExclusion Criteria:\n\n* A patient with at least one of the following conditions will be excluded:\n\n  1. Received bendamustine treatment within the past 9 months;\n  2. Intracranial hypertension or impaired consciousness in the brain;\n  3. Symptomatic heart failure or severe arrhythmia;\n  4. Symptoms of severe respiratory failure;\n  5. With other types of malignant tumors;\n  6. Disseminated intravascular coagulation;\n  7. Serum creatinine and\u002For blood urea nitrogen ≥ 1.5 times the normal value;\n  8. Suffering from sepsis or other uncontrollable infections;\n  9. Uncontrollable diabetes;\n  10. Severe mental disorders;\n  11. Significant lesions in the brain as detected by head magnetic resonance imaging;\n  12. Leukemic cells in the cerebrospinal fluid \\>20 cells\u002FμL;\n  13. Peripheral blood leukemic cell proportion \\>30%;\n  14. Have undergone organ transplantation;\n  15. Female patients (those with childbearing potential) are pregnant or lactating;\n  16. Active or uncontrollable infectious diseases, such as hepatitis (HBV, HCV), HIV, or syphilis.","39 Years",{"count":161,"type":20},213,[121],"This is a single-center, double-blind, randomized trial. Patients with relapsed or refractory acute B-lymphoblastic leukemia(r\u002Fr B-ALL) experiencing early functional exhaustion of CAR-T cells will be randomly allocated into three groups: the control cell group, the CIK treatment group, and the messenger RNA(mRNA)-CIK treatment group. The primary objective of the study is to evaluate the prognostic impact of CIK cell therapy on the early functional exhaustion of CAR-T cells in children and adolescent and young adult (AYA) with r\u002Fr B-ALL. The primary endpoint of the study is the event-free survival rate of these patient in the CIK cell therapy group.A total number of 213 subjects will be enrolled.",[124,26,125],"2026-02-24",{"date":167,"type":33},"2026-02-25",{"date":169,"type":33},"2024-05-27",{"date":171,"type":20},"2026-05-30",{"name":109,"class":40},{"id":174,"slug":175,"hasResults":11,"nctId":176,"briefTitle":177,"officialTitle":177,"acronym":178,"eligibilityCriteria":179,"healthyVolunteers":11,"sex":16,"minAge":49,"maxAge":92,"enrollmentInfo":180,"targetDuration":4,"studyType":21,"phases":181,"briefSummary":97,"conditions":182,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":183,"lastUpdatePostDateStruct":184,"startDateStruct":186,"completionDateStruct":188,"leadSponsor":190,"locationsCount":110},"100598348","phase-1-a-multicenter-open-label-non-randomized-single-arm-clinical-study-of-nanobody-cd5-car-t-cell-therapy-for-refractoryrelapsed-t-lymphocyte-malignancies-100598348","NCT07070323","A Multicenter, Open-Label, Non-Randomized, Single-Arm Clinical Study of Nanobody CD5-CAR T Cell Therapy for Refractory\u002FRelapsed T Lymphocyte Malignancies","nanobody CD5","Inclusion Criteria:\n\nOnly patients who meet all the following criteria can be included:\n\n1\\. Candidates with relapse or refractory CD5+ T-cell malignancies, who have progressed after treatment with all standard therapies or been intolerant of standard care, have limited prognosis with currently available therapies and have no available curative treatment options (such as stem-cell transplantation (SCT) or chemotherapy); 2. For subjects who received autologous CD5 CAR T cells, the tumor burden in peripheral blood is less than 20%, and suspending anti-neoplastic treatment for more than 2 weeks; 3. Aged 1-70 years; 4. No severe allergy; 5. Eastern Cooperative Oncology Group (ECOG) performance status 1 score 0 to 2; 6. Patients are expected to live for at least 60 days; 7. CD5+ on blasts in bone marrow (BM) or cerebrospinal fluid (CSF) and tumor tissues by flow cytometry and immunohistochemistry, respectively. (Positive rate \\>80% by flow cytometry with less than one log difference in mean fluorescence intensity from normal T cells, or positive rate \\>30% positive by immunohistochemistry); 8. Provide a signed informed consent before any screening procedure. Subjects who voluntarily participate in the study should have the ability to understand and sign the informed consent form and be willing to follow the study visit schedule and relevant study procedure, as specified in the protocol. Candidates aged 19-70 years need to be sufficiently conscious and able to sign the treatment consent form and voluntary consent form. Children candidates of 8-18 years old need to be sufficiently conscious and able to sign the treatment consent form and voluntary consent form and their legal guardian or patient advocate has also need to sign the treatment consent form and voluntary consent form, respectively. Children candidates of 1-7 can be recruited after the legal guardian or patient advocate has signed the treatment consent form and voluntary consent form; 9. Have available allogeneic hematopoietic stem cell transplantation donor for the subject who received newly matched donor-derived CD5 CAR T cells, and is willing to perform SCT when CR is achieved.\n\n\\-\n\nExclusion Criteria:\n\nPatients with at least one of the following conditions are excluded:\n\n1\\. Impaired consciousness or intracranial hypertension; 2. Symptomatic congestive heart failure or severe cardiac arrhythmia; 3. Manifestations of severe respiratory system failure; 4. Co-existence with other malignancies; 5. Disseminated intravascular coagulation; 6. Serum creatinine and\u002For blood urea nitrogen (BUN) ≥ 1.5-fold upper limit; 7. Sepsis or other uncontrollable infections; 8. Uncontrollable diabetes; 9. Serious mental illness; 10. Apparent and active intracranial lesions on cranial magnetic resonance imaging (MRI); 11. Underwent organ transplantation, excepting SCT; 12. Pregnant females; 13. Positive test for infectious hepatitis, acquired immune deficiency syndrome (AIDS) or syphilis; 14. Post-CAR SCT is not feasible in patients who plan to receive newly matched donor-derived CD5 CAR T cells; 15. Inability to collect peripheral blood mononuclear cells (PBMC) or no frozen PBMC available for CAR T cell manufacturing.\n\n\\-",{"count":94,"type":20},[23,96],[99,26,100,101],"2025-11-21",{"date":185,"type":33},"2025-11-26",{"date":187,"type":33},"2025-07-09",{"date":189,"type":20},"2026-12-31",{"name":109,"class":40},{"id":192,"slug":193,"hasResults":11,"nctId":194,"briefTitle":195,"officialTitle":196,"acronym":4,"eligibilityCriteria":197,"healthyVolunteers":11,"sex":16,"minAge":49,"maxAge":92,"enrollmentInfo":198,"targetDuration":4,"studyType":21,"phases":200,"briefSummary":201,"conditions":202,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":183,"lastUpdatePostDateStruct":204,"startDateStruct":205,"completionDateStruct":207,"leadSponsor":209,"locationsCount":110},"100540406","phase-1-autologous-and-donor-derived-cd7-car-t-therapy-in-refractory-or-relapsed-t-cell-malignancies-100540406","NCT06316427","Autologous and Donor-derived CD7 CAR-T Therapy in Refractory or Relapsed T-cell Malignancies","Autologous and Donor-derived CD7 CAR T-cell Therapy in Refractory or Relapsed T-cell Malignancies: a Multi-center, Open-label, Phase Ⅰ\u002FⅡ Clinical Trial","Inclusion Criteria:\n\nOnly patients who meet all the following criteria can be included in the group:\n\n1. CD7-positive refractory or relapsed T-cell malignancies with progression or intolerance after all standard treatments, limited prognosis from currently available treatments and no available treatment options (e.g. HSCT or chemotherapy).\n2. Tumor cells in bone marrow or cerebrospinal fluid are positive for CD7 antigen by flow cytometry or tumour tissue is positive for CD7 by immunohistochemistry (CD7 antigen positivity by flow cytometry: \\>80% of tumour cells expressing CD7 with a mean fluorescence intensity \\[MFI\\] of CD7 similar to that of normal T cells are considered to have fully positive expression; \\>80% of tumor cells expressing CD7 but with an MFI of CD7 at least 1 log lower than that of normal T cells are considered to have low expression \\[dim\\]; tumor cells with a CD7 expression rate between 20-80% are considered to have partial expression; CD7 antigen positivity by pathological immunohistochemistry: \\>30%);\n3. Male or female, age 1-70 years;\n4. No severe allergic constitution;\n5. Eastern Cooperative Oncology Group (ECOG) performance status score (Oken et al., 1982) of 0-2;\n6. Life expectancy of at least 60 days as determined by the investigator;\n7. Provide a signed informed consent form prior to any screening procedures; subjects volunteering to participate in the study should be capable of understanding and signing the informed consent form and be willing to follow the study visit schedule and associated study procedures as specified in the protocol. Subjects aged 19-70 years old need to be sufficiently aware and capable of signing the informed consent form; subjects aged 1-7 years can be recruited after legal guardians or patient advocates sign the informed consent form; subjects aged 8-18 years need to be sufficiently aware and able to sign the informed consent form, and their legal guardians or patient advocates also need to sign the informed consent form.\n\nExclusion Criteria:\n\nPatients with at least one of the following conditions are excluded:\n\n1. Intracranial hypertension or unconscious;\n2. Acute heart failure or severe arrhythmia;\n3. Acute respiratory failure;\n4. Other types of malignant tumors;\n5. Diffuse intravascular coagulation;\n6. Serum creatinine and\u002For blood urea nitrogen over 1.5 times the normal value;\n7. Sepsis or other uncontrolled infection;\n8. Uncontrolled diabetes mellitus;\n9. Severe psychological disorder;\n10. Obvious cranial lesions by cranial MRI;\n11. Allergic constitution;\n12. Organ recipients;\n13. Pregnant or breastfeeding;\n14. Active, uncontrolled infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or treponema pallidum (TP).",{"count":199,"type":20},80,[23,96],"This is a multi-center, open-label, non-randomized, phase I\u002FII trial. Patients with refractory or relapsed T-cell malignancies will receive autologous, prior-HSCT donor-derived or new donor-derived CD7 CAR T cells according to their HSCT history, peripheral blood leukemia burden and at their discretion. The primary objective is to learn about the safety of autologous, prior-HSCT donor-derived and new donor-derived CD7 CAR T-cell therapy in patients with refractory or relapsed T-cell acute lymphoblastic leukemia and lymphoma (r\u002Fr T-ALL\u002FT-LBL) in phase I and to learn about the efficacy of autologous, prior-HSCT donor-derived and new donor-derived CD7 CAR T-cell therapy in patients with refractory or relapsed T-cell acute lymphoblastic leukemia and lymphoma (r\u002Fr T-ALL\u002FT-LBL) in phase II. The primary endpoint is type and incidence of dose limiting toxicity (DLT) within 21 days after CD7 CAR T-cell infusion in phase I and overall response rate (ORR), which includes CR, CRh, CRi, MLFS, aplastic marrow for blood and bone marrow; central nervous system (CNS) remission; CR and PR for lymphomatous extramedullary disease according to National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2023 of Acute Lymphoblastic Leukemia at 3 months (± 1 week) post CD7 CAR T-cell infusion in refractory or relapsed T-cell acute lymphoblastic leukemia\u002Flymphoma (r\u002Fr T-ALL\u002FT-LBL) patients treated with CD7 CAR T cells in phase II. A total number of 80 subjects will be enrolled.",[203,26,100,101],"T-cell Acute Lymphoblastic Leukemia",{"date":185,"type":33},{"date":206,"type":33},"2024-03-22",{"date":208,"type":20},"2028-03-30",{"name":109,"class":40},{"id":211,"slug":212,"hasResults":11,"nctId":213,"briefTitle":214,"officialTitle":215,"acronym":216,"eligibilityCriteria":217,"healthyVolunteers":11,"sex":16,"minAge":218,"maxAge":92,"enrollmentInfo":219,"targetDuration":4,"studyType":21,"phases":220,"briefSummary":221,"conditions":222,"keywords":228,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":231,"lastUpdatePostDateStruct":232,"startDateStruct":234,"completionDateStruct":236,"leadSponsor":238,"locationsCount":41},"100493470","phase-1-clinical-trial-using-car--t-cells-for-treatment-of-patients-with-refractory-or-relapsed-cd19-positive-b-lymphoid-malignancies-100493470","NCT05705570","Clinical Trial Using CAR- T Cells for Treatment of Patients With Refractory or Relapsed CD19-positive B Lymphoid Malignancies","A Phase I Clinical Trial Using Genetically Engineered Autologous T Cells to Express Chimeric Antigen Receptor (CAR) for Treatment of Patients With Refractory or Relapsed CD19-positive B Lymphoid Malignancies","CARTHIAE-1","Inclusion Criteria:\n\n1. Subjects must have relapsed or refractory ALL, lymphoma or CLL treated with at least two lines of therapy. Disease must have either progressed after the last regimen or presented failure to achieve partial or complete remission with the last regimen.\n\n   Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) subjects are eligible if they progressed, had stable disease or relapsed after two lines of therapy, including tyrosine kinase inhibitors (TKIs).\n\n   Subjects with DLBCL must have progressed, had SD, or recurred after initial treatment regimens that include an anthracycline and an anti-CD20 monoclonal antibody.\n\n   Subjects with transformed FL, MZL, or CLL\u002FSLL must have progressed, had SD or recurred with transformed disease after initial treatment for DLBCL.\n\n   Subjects who relapse ≥12 months after therapy should have progressed after autologous transplant or been ineligible for autologous transplant.\n2. 2\\. The patient's disease must be CD19 positive, either by immunohistochemistry or flow cytometry analysis on the last biopsy available.\n3. Age 2 to 70 years.\n4. Performance status: Adult Subjects: ECOG ≤ 2 for patients ≥ 16 years; Subjects \\\u003C 16 years of age: lansky ≥ 50%\n5. Normal Organ and Marrow Functioning (supportive treatment is allowed according to institutional standards, i.e. filgrastim, transfusion)\n\n   • Total Bilirubin ≤ 2; AST (SGOT) ≤ 5 times the upper limit of normal; ALT (SGTP) ≤ 5 times the upper limit of normal; Serum creatinine ≤ 1.5; Pulse oximetry \\>91% on room air; No dyspnea or mild dyspnea (≤ Grade 1); Forced expiratory volume in 1 s (FEV1) ≥50% or carbon monoxide diffusion test (DLCO) ≥50% of predicted level; Left ventricular ejection fraction ≥ 45% confirmed by echocardiogram; Subjects must have the following hematologic function parameters: Neutrophils \\> 1000\u002FuL; Absolute Lymphocyte Count \\> 100\u002FuL; Platelets ≥ 50,000\u002FL Patient should not be excluded if change of the above parameters due to spinal cord disease infiltration;\n6. Prior therapy wash-out - At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory\u002Fstimulatory immune checkpoint therapy, which requires 5 half-lives, Blinatumomab with 4 months prior CAR-T infusion.\n7. For women of reproductive potential: use a highly effective contraceptive for at least 1 month prior to screening and agree to use a method during study participation and for an additional 4 months after CAR T-cell administration has ended.\n8. Subjects must have the ability to understand and the willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\n1. Autologous transplant within 6 weeks of planned CAR-T cell infusion;\n2. History of allogeneic stem cell transplant 4 months prior CAR T cell infusion.\n3. Use of immunosuppression therapy;\n\n   • Patients must have completed immunosuppression therapy; Systemic corticosteroid therapy must be stopped more than 72 hours after infusion; Systemic drugs for graft-versus-host disease should be withheld at least 4 weeks prior to infusion;\n4. Presence of graft-versus-host disease Grade ≥ 2;\n5. Receiving CAR T cell treatment outside of this protocol;\n6. Active central nervous system or meningeal involvement by tumor. Subjects with untreated brain metastases\u002FCNS disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of CNS or meningeal involvement must be in a documented remission by CSF evaluation and contrast-enhanced MRI imaging for at least 90 days prior to registration.\n7. History of active malignancy other than non-melanoma skin cancer, carcinoma in situ (e.g. cervix, bladder, breast).\n8. HIV infection; HTLV\n9. Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n10. Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects.\n11. Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy\n12. Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.)\n13. Serious and\u002For potentially fatal medical conditions\n14. Patients with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease.\n15. History of autoimmune disease (i.e. rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months.\n16. Hypersensitivity against any drug or its ingredients\u002Fimpurities that is scheduled or likely to be given during trial participation, e.g. as part of the mandatory lymphodepletion protocol, pre-medication for infusion, rescue medication\u002Fsalvage therapies for treatment related toxicities;","2 Years",{"count":52,"type":20},[23],"This is a phase l, single arm, prospective open, dose-escalation study in patients with relapsed or refractory CD19-positive B cell malignancies (ALL, NHL, CLL). The trial will include adult and pediatric patients. There will be three individual cohorts, defined by disease biology: pediatric ALL and aggressive pediatric NHL (Cohort 1), adult ALL (Cohort 2) and adult NHL\u002FCLL (Cohort 3).",[26,223,224,225,226,227],"Acute Lymphoblastic Leukemia Refractory","B-cell Lymphoma Recurrent","B-cell Lymphoma Refractory","Chronic Lymphocytic Leukemia Recurrent","Chronic Lymphocytic Leukemia Refractory",[229,230],"CAR T cell","CD19+ B-cell Malignancies","2025-09-22",{"date":233,"type":33},"2025-09-25",{"date":235,"type":33},"2023-02-07",{"date":237,"type":20},"2028-12-01",{"name":239,"class":40},"Nelson Hamerschlak",{"id":241,"slug":242,"hasResults":11,"nctId":243,"briefTitle":244,"officialTitle":245,"acronym":246,"eligibilityCriteria":247,"healthyVolunteers":11,"sex":16,"minAge":49,"maxAge":17,"enrollmentInfo":248,"targetDuration":4,"studyType":21,"phases":250,"briefSummary":251,"conditions":252,"keywords":257,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":268,"lastUpdatePostDateStruct":269,"startDateStruct":271,"completionDateStruct":273,"leadSponsor":275,"locationsCount":277},"100496552","phase-1-hem-ismart-c-ruxolitinib--venetoclax--dexamethasone--cyclophosphamide-and-cytarabine-in-pediatric-patients-with-relapsed-or-refractory-hematological-malignancies-100496552","NCT05745714","HEM-iSMART-C: Ruxolitinib + Venetoclax + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With Relapsed or Refractory Hematological Malignancies","International Proof of Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory HEMatological Malignancies in Children, Subprotocol C Ruxolitinib + Venetoclax + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With Relapsed or Refractory Hematological Malignancies","HEM-iSMART C","Inclusion Criteria:\n\n1. Children between 1 year (≥ 12 months) and 18 years of age at the time of first diagnosis and less than 21 years at the time of inclusion\n2. Performance status: Karnofsky performance status (for patients \\>12 years of age) or Lansky Play score (for patients ≤12 years of age) ≥ 50% (Appendix I).\n3. Written informed consent from parents\u002Flegal representative, patient, and age-appropriate assent before any study specific screening procedures are conducted, according to local, regional or national guidelines.\n4. Patients must have had advanced molecular profiling and flow-cytometric analysis of their recurrent or refractory disease at a time-point before the first inclusion into this trial (see section 9.1 for detailed description of the molecular diagnostics required). Drug response profiling and methylation is highly recommended but not mandatory. Patients with molecular profiling at first diagnosis lacking molecular diagnostics at relapse or refractory disease may be allowed to be included after discussion with the sponsor.\n5. Patients whose tumor presents alterations in the IL-7R and\u002For JAK-STAT signaling pathways including but not limited to the following are eligible: CRLF2: Rearrangements and mutations leading to CRLF2 overexpression (P2RY8-CRLF2, IGH-CRLF2, and CRLF2 F232C), CRFL2 overexpression; EPOR: Truncating rearrangements or mutations in exon 8, EPOR fusions; JAK1\u002F2\u002F3: Recurrent or novel missense and in-frame indel mutations in or flanking the pseudokinase and kinase domains, JAK fusion; IL7R: Recurrent or novel missense or in-frame indel mutations in the transmembrane domain; SH2B3: Copy number deletions, or mutations that result in frameshifts or premature termination; JAK2: In frame fusions retaining the tyrosine kinase domain; USP9X truncating mutation or USP9X-DDX3X fusion; STAT5B and DNM2 mutations; PTPN2 deletion described as involved in IL7R\u002FJAK\u002FSTAT pathway activation; IL7R mutations\n6. Adequate organ function:\n\n   * RENAL AND HEPATIC FUNCTION (Assessed within 48 hours prior to C1D1) :\n\n     * Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age or calculated creatinine clearance as per the Schwartz formula or radioisotope glomerular filtration rate ≥ 60 mL\u002Fmin\u002F1.73 m2.\n     * Direct bilirubin ≤ 2 x ULN (≤ 3.0 × ULN for patients with Gilbert's syndrome).\n     * Alanine aminotransferase (ALT)\u002Fserum glutamic pyruvic transaminase (SGPT) ≤ 5 x ULN; aspartate aminotransferase (AST)\u002Fserum glutamic oxaloacetic transaminase\u002FSGOT ≤ 5 x ULN. Note: Patients with hepatic disfunction related to the underling disease can be eligible even if they do not fulfill the aforementioned values for hepatic transaminases. In these cases, patients need to be discussed with the sponsor to confirm the eligibility.\n   * CARDIAC FUNCTION:\n\n     * Shortening fraction (SF) \\>29% (\\>35% for children \\\u003C 3 years) and\u002For left ventricular ejection fraction (LVEF) ≥50% at baseline, as determined by echocardiography or MUGA.\n     * Absence of QTcF prolongation (QTc prolongation is defined as \\>450 msec on baseline ECG, using the Friedericia correction), or other clinically significant ventricular or atrial arrhythmia.\n\n   Exclusion Criteria:\n7. Pregnancy or positive pregnancy test (urine or serum) in females of childbearing potential. Pregnancy test must be performed within 7 days prior to C1D1.\n8. Sexually active participants not willing to use highly effective contraceptive method (pearl index \\\u003C1) as defined in CTFG HMA 2020 (Appendix II) during trial participation and until 6 months after end of antileukemic therapy.\n9. Breast feeding.\n10. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome) in case of oral IMPs.\n11. Patients whose tumor present known mutationts confering resistance to JAK inhibitors: JAK1 Phe958 and Pro960 mutations and JAK2 Y931C mutations.\n12. Patients whose tumor present known mutationts confering resistance to venetoclax (e.g. BCL2 mutations of venetoclax binding-site (Gly101Val mutation, Phe104Leu\u002FCys mutations).\n13. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to the study drugs, or drugs chemically related to study treatment or excipients that contraindicate their participation, including conventional chemotherapeutics (i.e. cytarabine and cyclophosphamide when applicable, intrathecal agents) and corticoids.\n14. Known active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection.\n15. Severe concomitant disease that does not allow treatment according to the protocol at the investigator's discretion.\n16. Subjects unwilling or unable to comply with the study procedures.\n17. Previous treatment with ruxolitinib and venetoclax in combination (Patients who have previously received any of these two drugs separately can be eligible for this sub-protocol).\n18. Current use of a prohibited medication or herbal preparation or requires any of these medications during the study. See Section 7, Appendix III and IV for details. In general, CYP3A4 inhibitors\u002FPgp inhibitors, moderate or strong inducers of CYP3A4 or drugs inducing QTc changes (prolongation of the QT interval or inducing Torsade de Points) are not permitted. Among others and not exclusively that relates to antiviral, antifungal, antibiotic, antimalarial, antipsychotic and antidepressive drugs.\n19. Patients who have consumed grapefruit, grapefruit products, Seville oranges (Including marmalade containing Seville oranges) or starfruit within 72 hours prior to the first dose of study drug.\n20. Unresolved toxicity greater than NCI CTCAE v 5.0 ≥ grade 2 from previous anti-cancer therapy, including major surgery, except those that in the opinion of the investigator are not clinically relevant given the known safety\u002Ftoxicity profile of the study treatment (e.g., alopecia and\u002For peripheral neuropathy related to platinum or vinca alkaloid based chemotherapy) (Common Terminology Criteria for Adverse Events (CTCAE) (cancer.gov).\n21. Active acute graft versus host disease (GvHD) of any grade or chronic GvHD of grade 2 or higher. Patients receiving any agent to treat or prevent GvHD post bone marrow transplant are not eligible for this trial.\n22. Received immunosuppression post allogenic HSCT within one moth of study entry.\n23. History of bone disorders such as osteogenesis imperfecta, rickets, renal osteodystrophy, osteomyelitis, osteopenia, fibrous dysplasia, osteomalacia etc. prior to the underlying diagnosis.\n24. History of progressive multifocal leuko-encephalopathy (PML).\n25. History of endocrine or kidney related growth retardation prior to the underlying diagnosis.\n26. Evidence of clinically active tuberculosis (clinical diagnosis per local practice).\n27. Wash-out periods of prior medication:\n\n    1. CHEMOTHERAPY: At least 7 days must have elapsed since the completion of cytotoxic therapy, with the exception of hydroxyurea, 6-mercaptopurine, oral methotrexate and steroids which are permitted up until 48 hours prior to initiating protocol therapy. Patients may have received intrathecal therapy (IT) at any time prior to study entry.\n    2. RADIOTHERAPY: Radiotherapy (non-palliative) within 21 days prior to the first dose of drug. Palliative radiation in past 21 days is allowed.\n    3. HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT):\n\n       * Autologous HSCT within 2 months prior to the first study drug dose.\n       * Allogeneic HSCT within 3 months prior to the first study drug dose.\n    4. IMMUNOTHERAPY: At least 42 days must have elapsed after the completion of any type of immunotherapy other than monoclonal antibodies (e.g. CAR-T therapy)\n    5. MONOCLONAL ANTIBODIES AND INVESTIGATIONAL DRUGS: At least 21 days or 5 times the half-life (whichever is shorter) from prior treatment with monoclonal antibodies or any investigational drug under investigation must have elapsed before the first study drug.\n    6. SURGERY: Major surgery within 21 days of the first dose. Gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumor biopsy and insertion of central venous access devices are not considered major surgery.",{"count":249,"type":20},26,[23,96],"HEM-iSMART is a master protocol which investigates multiple investigational medicinal products in children, adolescents and young adults (AYA) with relapsed\u002Frefractory (R\u002FR) ALL and LBL. Sub-protocol C is a phase I\u002FII trial evaluating the safety and efficacy of ruxolitinib and venetoclax in combination with dexamethasone, cyclophosphamide and cytarabine in children and AYA with R\u002FR ped ALL\u002FLBL whose tumor present with alterations in the IL7R\u002FJAK-STAT pathway.",[26,253,254,255,256],"Lymphoblastic Lymphoma (Precursor B-Lymphoblastic Lymphoma\u002FLeukaemia) Recurrent","Lymphoblastic Lymphoma (Precursor T-Lymphoblastic Lymphoma\u002FLeukaemia) Recurrent","Lymphoblastic Lymphoma (Precursor B-Lymphoblastic Lymphoma\u002FLeukaemia) Refractory","Lymphoblastic Lymphoma (Precursor T-Lymphoblastic Lymphoma\u002FLeukaemia) Refractory",[258,259,260,261,262,263,264,265,266,267],"acute lymphoblastic leukemia","Lymphoblastic lymphoma","Biomarker driven clinical trial","Ruxolitinib","Venetoclax","Chemotherapy","Relapse","Children","Adolescents","Young adults","2025-09-09",{"date":270,"type":33},"2025-09-16",{"date":272,"type":20},"2025-10-01",{"date":274,"type":20},"2032-02-02",{"name":276,"class":40},"Princess Maxima Center for Pediatric Oncology",33,{"id":279,"slug":280,"hasResults":11,"nctId":281,"briefTitle":282,"officialTitle":283,"acronym":284,"eligibilityCriteria":285,"healthyVolunteers":11,"sex":16,"minAge":49,"maxAge":17,"enrollmentInfo":286,"targetDuration":4,"studyType":21,"phases":287,"briefSummary":288,"conditions":289,"keywords":290,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":268,"lastUpdatePostDateStruct":294,"startDateStruct":295,"completionDateStruct":297,"leadSponsor":299,"locationsCount":300},"100489862","phase-1-hem-ismart-d-trametinib--dexamethasone--chemotherapy-in-children-with-relapsed-or-refractory-hematological-malignancies-100489862","NCT05658640","HEM iSMART-D: Trametinib + Dexamethasone + Chemotherapy in Children With Relapsed or Refractory Hematological Malignancies","International Proof of Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory HEMatological Malignancies in Children, Subprotocol D: Trametinib + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With Relapsed or Refractory Hematological Malignancies","HEM-iSMART D","Inclusion criteria\n\n1. Children between 1 year (≥ 12 months) and 18 years of age at the time of first diagnosis and less than 21 years at the time of inclusion. Patients under 6 years old must weigh at least 7 kg at the time of enrollment. Patients over 6 years old must weigh at least 10 kg at the time of enrollment.\n2. Performance status: Karnofsky performance status (for patients \\>12 years of age) or Lansky Play score (for patients\n\n   * 12 years of age) ≥ 50% (Appendix I).\n3. Written informed consent from parents\u002Flegal representative, patient, and age-appropriate assent before any study specific screening procedures are conducted, according to local, regional or national guidelines.\n4. Patients must have had molecular profiling and flow-cytometric analysis of their recurrent or refractory disease at a time-point before the first inclusion into this trial (see section 9.1 of this protocol for detailed description of the molecular diagnostics required). Drug response profiling and methylation is highly recommended but not mandatory.\n\n   Patients with molecular profiling at first diagnosis lacking molecular diagnostics at relapse or refractory disease may be allowed to be included after discussion with the sponsor.\n5. Patients whose tumor present RAS pathway activating mutations including but not limited to KRAS, NRAS, HRAS, FLT3, PTPN11, MAP2K1, MP2K1 hotspot mutations, cCBL; NF1 del, as detected by molecular profiling.\n6. Adequate organ function:\n\n   * RENAL AND HEPATIC FUNCTION (Assessed within 48 hours prior to C1D1) :\n\n     * Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age or calculated creatinine clearance as per the Schwartz formula or radioisotope glomerular filtration rate ≥ 60 mL\u002Fmin\u002F1.73 m2.\n     * Direct bilirubin ≤ 2 x ULN (≤ 3.0 × ULN for patients with Gilbert's syndrome).\n     * Alanine aminotransferase (ALT)\u002Fserum glutamic pyruvic transaminase (SGPT) ≤ 5 x ULN; aspartate aminotransferase (AST)\u002Fserum glutamic oxaloacetic transaminase\u002FSGOT ≤ 5 x ULN. Note: Patients with hepatic disfunction related to the underling disease can be eligible even if they do not fulfill the aforementioned values for hepatic transaminases. In these cases, patients need to be discussed with the sponsor to confirm the eligibility.\n   * CARDIAC FUNCTION:\n\n     * Shortening fraction (SF) \\>29% (\\>35% for children \\\u003C 3 years) and\u002For left ventricular ejection fraction (LVEF) ≥50% at baseline, as determined by echocardiography or MUGA.\n     * Absence of QTcF prolongation (QTc prolongation is defined as \\>450 msec on baseline ECG, using the Fridericia correction), or other clinically significant ventricular or atrial arrhythmia.\n\n   Exclusion Criteria\n7. Pregnancy or positive pregnancy test (urine or serum) in females of childbearing potential. Pregnancy test must be performed within 7 days prior to C1D1.\n8. Sexually active participants not willing to use highly effective contraceptive method (pearl index \\\u003C1) as defined in CTFG HMA 2020 (Appendix II) during trial participation and until 6 months after end of antileukemic therapy.\n9. Breast feeding.\n10. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome) in case of oral IMPs.\n11. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to the study drugs, or drugs chemically related to study treatment or excipients that contraindicate their participation, including conventional chemotherapeutics (i.e. cytarabine and cyclophosphamide, intrathecal agents) and corticoids.\n12. Known active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection.\n13. Severe concomitant disease that does not allow treatment according to the protocol at the investigator's discretion.\n14. Subjects unwilling or unable to comply with the study procedures.\n15. Previous treatment with trametinib.\n16. Current use of a prohibited medication or herbal preparation or requires any of these medications during the study.\n\n    See Section 7 and Appendix III for details. Drugs inducing QTc changes (prolongation of the QT interval or inducing Torsade de Points) are not permitted.\n17. Unresolved toxicity greater than NCI CTCAE v 5.0 ≥ grade 2 from previous anti-cancer therapy, including major surgery, except those that in the opinion of the investigator are not clinically relevant given the known safety\u002Ftoxicity profile of the study treatment (e.g., alopecia and\u002For peripheral neuropathy related to platinum or vinca alkaloid based chemotherapy) (Common Terminology Criteria for Adverse Events (CTCAE) (cancer.gov).\n18. Active acute graft versus host disease (GvHD) of any grade or chronic GvHD of grade 2 or higher. Patients receiving any agent to treat or prevent GvHD post bone marrow transplant are not eligible for this trial.\n19. Received immunosuppression post allogenic HSCT within one moth of study entry.\n20. History or current evidence of retina vein occlusion (RVO) or central serous retinopathy are excluded.\n21. Wash-out periods of prior medication:\n\n    1. CHEMOTHERAPY: At least 7 days must have elapsed since the completion of cytotoxic therapy, with the exception of hydroxyurea, 6-mercaptopurine, oral methotrexate and steroids which are permitted up until 48 hours prior to initiating protocol therapy. Patients may have received intrathecal therapy (IT) at any time prior to study entry.\n    2. RADIOTHERAPY: Radiotherapy (non-palliative) within 21 days prior to the first dose of drug. Palliative radiation in past 21 days is allowed.\n    3. HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT): Autologous HSCT within 2 months prior to the first study drug dose; Allogeneic HSCT within 3 months prior to the first study drug dose.\n    4. IMMUNOTHERAPY: At least 42 days must have elapsed after the completion of any type of immunotherapy other than monoclonal antibodies (e.g. CAR-T therapy)\n    5. MONOCLONAL ANTIBODIES AND INVESTIGATIONAL DRUGS: At least 21 days or 5 times the half-life (whichever is shorter) from prior treatment with monoclonal antibodies or any investigational drug under investigation must have elapsed before the first study drug.\n    6. SURGERY: Major surgery within 21 days of the first dose. Gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumor biopsy and insertion of central venous access devices are not considered major surgery.",{"count":249,"type":20},[23,96],"HEM-iSMART is a master protocol which investigates multiple investigational medicinal products in children, adolescents and young adults (AYA) with relapsed\u002Frefractory (R\u002FR) ALL and LBL. Sub-protocol D is a phase I\u002FII trial evaluating the safety and efficacy of trametinib in combination with dexamethasone, cyclophosphamide and cytarabine in children and AYA with R\u002FR ped ALL\u002FLBL whose tumor present with alterations in the RAS-RAF-MAPK pathway.",[26,253,254,255,256],[291,259,260,292,263,264,293,265,266,267],"Acute lymphoblastic leukemia","Trametinib","Refractory",{"date":270,"type":33},{"date":296,"type":33},"2023-11-14",{"date":298,"type":20},"2029-04-01",{"name":276,"class":40},36,{"id":302,"slug":303,"hasResults":11,"nctId":304,"briefTitle":305,"officialTitle":306,"acronym":4,"eligibilityCriteria":307,"healthyVolunteers":11,"sex":16,"minAge":4,"maxAge":308,"enrollmentInfo":309,"targetDuration":4,"studyType":21,"phases":311,"briefSummary":313,"conditions":314,"keywords":319,"overallStatus":322,"whyStopped":4,"lastUpdateSubmitDate":323,"lastUpdatePostDateStruct":324,"startDateStruct":326,"completionDateStruct":328,"leadSponsor":330,"locationsCount":41},"100499182","early-phase-1-safety-and-feasibility-of-cd19-car-t-cells-using-clinimacs-prodigy-for-relapsedrefractory-cd19-positive-all-and-nhl-100499182","NCT05779930","Safety and Feasibility of CD19 CAR T Cells Using CliniMACS Prodigy for Relapsed\u002FRefractory CD19 Positive ALL and NHL","Safety and Feasibility of On-Site Manufacture of CD19 CAR T Cells Using the CliniMACS Prodigy in Pediatric and Young Adult Patients With Relapsed\u002FRefractory CD19 Positive Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma","Eligible Diseases:\n\nRelapsed or refractory pediatric B-Cell ALL as defined by at least one of the following criteria:\n\n* Second or greater relapse OR\n* Any relapse after allogeneic SCT OR\n* Not achieving a CR after 2 cycles of standard chemotherapy regimen (including persistent MRD positive disease) OR\n* Not achieving a CR after 1 cycle of standard chemotherapy for relapsed leukemia (including persistent MRD positive disease) OR\n* Patients with Philadelphia chromosome positive (Ph+) ALL who are intolerant or have failed 3 lines of tyrosine kinase inhibitor (TKI) therapy, or if TKI therapy is contraindicated OR\n* Patients who meet accepted indications for allogeneic HSCT for pediatric ALL but are deemed unfit for HSCT by their treating physician are eligible for this study. This includes high risk patients in first relapse.\n\nPatients with relapsed or refractory pediatric B cell non-Hodgkin's Lymphoma as defined by:\n\n* Refractory to second-line or later lines of standard chemotherapy OR\n* Patients with residual disease after primary therapy and not eligible for autologous SCT OR\n* Any relapse after previous allogeneic or autologous SCT OR\n* Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT\n\nNote: patients with a history of blinatumomab therapy are eligible for this study.\n\nInclusion Criteria:\n\n* For relapsed patients, CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry at most recent relapse or reconfirmed after CD19 directed therapy in ALL patients. For patients with NHL, documentation of CD19 positivity must be available from biopsy at diagnosis or most recent tumor biopsy.\n* Age 0 to age 30 at the time of initial diagnosis. Note: the first three subjects enrolled must be ≥16 years of age\n* Karnofsky (age ≥ 16 years) or Lansky (age \\\u003C 16 years) performance status ≥ 50 at screening\n* Patients with active CNS leukemia involvement defined as CNS-3 by CSF findings only are eligible but will have their infusion delayed until CNS disease is reduced to CNS-1 or CNS-2 by CSF findings. Patients with other forms of active CNS-3 leukemic involvement such as CNS parenchymal or ocular disease, cranial nerve involvement or significant leptomeningeal disease are eligible if there is documented evidence of disease stabilization for at least 1 month prior to CD19 CAR T cell infusion.\n* Meets criteria for non-hematopoietic organ function:\n\n  * Renal function: Estimated glomerular filtration rate ≥60 mL\u002Fmin x appropriate estimation of patient's body surface area m2\u002F1.73m2 using the modified Schwartz formula for pediatric patients and Crockcoft Gault formula for adults.\n  * Liver function: Total bilirubin ≤ 2 mg\u002Fdl or ≤ 2.5 x ULN for age (unless Gilbert's syndrome) and ALT and AST ≤ 5 x ULN for age (unless related to leukemic involvement)\n  * Cardiac function: left ventricular ejection fraction ≥40%\n  * Pulmonary function: minimum level of pulmonary reserve defined as ≤ grade 1 dyspnea and pulse oxygenation \\>91% on room air\n* Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator.\n* Signed consent by parent\u002Fguardian and assent if appropriate for subjects \\\u003C 18 years of age. Signed consent by patient\u002Fsubject if ≥18 years of age.\n\nExclusion Criteria:\n\n* Acute\u002Fongoing neurologic toxicity \\> Grade 1 with the exception of a history of controlled seizures or fixed neurologic deficits that have been stable\u002Fimproving over the past 1 months.\n* Active untreated infection. Viremia by PCR analysis is not considered an active infection but may require immediate viral prophylaxis. Patients with possible fungal infections must have had at least 2 weeks of appropriate anti-fungal therapy and be asymptomatic.\n* Patients with concomitant genetic syndrome: such as patients with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Patients with Down Syndrome will not be excluded.\n* Presence of Grade 2 to 4 acute or extensive chronic graft versus-host disease (GVHD) at the time of enrollment\n* Patient has participated in an investigational research study using an investigational agent within the last 30 days prior to screening\n* Pregnant or nursing (lactating) women.\n* Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening), or any uncontrolled infection at screening\n* HIV positive test within 8 weeks of screening\n* Allogeneic HSCT within 3 months of enrollment\n* Any prior CD19 CAR T cell therapy","30 Years",{"count":310,"type":20},12,[312],"EARLY_PHASE1","This pilot study examines the safety and efficacy of anti-CD19 CAR T cells manufactured on-site in children and young adults with relapsed or refractory CD19+ B cell acute lymphoblastic leukemia or CD19+ B cell non Hodgkin lymphoma.\n\nPatients will undergo screening, leukapheresis (cell collection), lymphodepleting chemotherapy with fludarabine and cyclophosphamide, followed by the anti-CD19 CAR T cell infusion. The lymphodepleting chemotherapy is administered over four days IV to prepare the body for the CAR T cells. The anti-CD19 CAR-T cells are infused between 2-14 days after the last dose of chemotherapy. This study is designed for participants to begin lymphodepleting chemotherapy during the CAR T cell manufacture and receive a fresh cell infusion on the day that manufacturing is complete. Some patients may need more time in between the cell collection and the CAR T cell infusion, therefore, the cells may be manufactured and frozen prior to administration. Patients will be followed for a year after the cell infusion on the study and for up to 15 years to monitor for potential long term side effects of cell therapy.",[26,315,316,61,317,318],"Non-Hodgkin's Lymphoma, Relapsed","Non-Hodgkin's Lymphoma Refractory","B-cell Non Hodgkin Lymphoma","B Cell Leukemia",[16,320,321],"NHL","CD19 CAR T cells","NOT_YET_RECRUITING","2025-08-13",{"date":325,"type":33},"2025-08-15",{"date":327,"type":20},"2025-10",{"date":329,"type":20},"2035-12",{"name":331,"class":40},"Nationwide Children's Hospital",{"id":333,"slug":334,"hasResults":11,"nctId":335,"briefTitle":336,"officialTitle":337,"acronym":338,"eligibilityCriteria":339,"healthyVolunteers":11,"sex":16,"minAge":218,"maxAge":340,"enrollmentInfo":341,"targetDuration":4,"studyType":21,"phases":343,"briefSummary":344,"conditions":345,"keywords":352,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":357,"lastUpdatePostDateStruct":358,"startDateStruct":360,"completionDateStruct":362,"leadSponsor":364,"locationsCount":41},"100532502","phase-1-fourth-gen-car-t-cells-targeting-cd19cd22-for-highly-resistant-b-cell-lymphomaleukemia-pmbclcns-bcl-100532502","NCT06213636","Fourth-gen CAR T Cells Targeting CD19\u002FCD22 for Highly Resistant B-cell Lymphoma\u002FLeukemia (PMBCL\u002FCNS-BCL).","T-cell Infusion Targeting CD19 and CD22 for Refractory\u002FRelapsed Leukemia\u002FLymphoma Patients With or Without Central Nervous System Involvement","BAH241","Inclusion Criteria:\n\n* Diagnosis: ALL In view of the PI and the primary oncologist, there must be no available alternative curative therapies or subject has declined to pursue alternative therapy; and subjects must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT, recurred after SCT, or have disease activity that prohibits SCT at the time of enrollment.\n* Chemotherapy refractory disease in subjects with B-ALL is defined as progression or stable disease after two lines of therapies\n* Recurrence of disease after achieving a complete response (CR).\n* Subjects with persistent or relapsed minimal residual disease (MRD) (by flow cytometry, PCR, FISH, or next generation sequencing) require verification of MRD positivity on two occasions at least 4 weeks apart.\n* Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) subjects are eligible if they progressed, had stable disease or relapsed after two lines of therapy, including tyrosine kinase inhibitors (TKIs).\n* Subjects with recurrence of isolated CNS relapse after achieving complete remission (CR); if relapsed with MRD, will require verification of MRD positivity on two occasions at least 4 weeks apart.\n* Diagnosis: Lymphoma Subjects with lymphoma must have progressed, had SD, or recurred after initial treatment regimens that include an anthracycline and an anti CD20 monoclonal antibody. Subjects who relapse ≥12 months after therapy should have progressed after autologous transplant or been ineligible for autologous transplant.\n* CD19 expression CD19 expression is required at any time since diagnosis. If patient has received anti-CD19 targeted therapy (i.e. Blinatumomab), then CD19 expression must be subsequently demonstrated. CD19 expression. must be detected on greater than 50% of the malignant cells by immunohistochemistry or ≥ 90% by flow cytometry. The choice of whether to use flow cytometry or immunohistochemistry will be determined by what is the most easily available tissue sample in each subject. In general, immunohistochemistry will be used for lymph node biopsies, flow cytometry will be used for peripheral blood and bone marrow samples.\n* Subjects who have undergone autologous SCT with disease progression or relapse following SCT will be eligible if all other eligibility criteria are met. Subjects who have undergone allogeneic SCT will be eligible if, in addition to meeting other eligibility criteria, they are at least 100 days post-transplant, they have no evidence of active GVHD and have been without immunosuppressive agents for at least 30 days.\n* Subjects who have undergone prior anti-CD19 or anti-CD22 CAR therapy will be eligible if \\\u003C 5% of circulating levels of CD3+ cells express the previous CAR by flow cytometry.\n* Must have evaluable or measurable disease; subjects with lymphoma must have evaluable or measurable disease according to the revised IWG Response Criteria for Malignant Lymphoma\\[66\\] must be present. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.\n* At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory\u002Fstimulatory immune checkpoint therapy, which requires 5 half-lives.\n* Exceptions:\n* There is no time restriction with regard to prior intrathecal chemotherapy (incl. steroids) provided there is complete recovery from any acute toxic effects of such; g. Subjects receiving hydroxyurea may be enrolled provided there has been no increase in dose for at least 2 weeks prior to starting apheresis; h. Subjects who are on standard ALL maintenance type chemotherapy (vincristine, 6-mercaptopurine or oral methotrexate) may be enrolled provided that chemotherapy is discontinued at least 1 week prior to apheresis.\n* Subjects receiving steroid therapy at physiologic replacement doses (≤ 5 mg\u002Fday of prednisone or equivalent doses of other corticosteroids) only are allowed provided there has been no increase in dose for at least 2 weeks prior to starting apheresis; j. For radiation therapy: Radiation therapy must have been completed at least 3 weeks prior to enrollment, with the exception that there is no time restriction if the volume of bone marrow treated is less than 10% and also the subject has measurable\u002Fevaluable disease outside the radiation port.\n* Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities, such as alopecia, nutritional support measures, electrolyte abnormalities, or those not impacting the investigator's ability to assess treatment emergent toxicities)\n* Age Greater than or equal to 1 year of age and less than or equal to 30 years of age at time of enrollment; must meet parameters for apheresis per institutional guidelines. NOTE: The first subject in the first dose cohort must be ≥ 18 years of age if an adult has not been treated at that dose cohort on the companion Stanford protocol \"Phase 1 Dose Escalation Study of CD19\u002FCD22 Chimeric Antigen Receptor (CAR) T Cells in Adults with Recurrent or Refractory B Cell Malignancies\" and undergone safety evaluation at Day 28 without evidence of DLT.\n* Performance Status: Subjects \\> 10 years of age: Karnofsky ≥ 50%; Subjects ≤ 10 years of age: Lansky scale ≥ 50% (See Appendix B Section 14.2)\n* Normal Organ and Marrow Function (supportive care is allowed per institutional standards, i.e. filgrastim, transfusion)\n* ANC ≥750\u002FuL\\*\n* Platelet count ≥50,000\u002FuL\\*\n* Absolute lymphocyte count ≥150\u002FuL\\*\n* Adequate renal, hepatic, pulmonary and cardiac function defined as:\n* Serum ALT\u002FAST ≤10 ULN (unless elevated ALT\u002FAST is attributed to leukemia or lymphoma involvement of the liver, in which case this criterion will be waived and not disqualify a patient).\n* Total bilirubin ≤1.5 mg\u002Fdl, except in subjects with Gilbert's syndrome.\n* Cardiac ejection fraction ≥ 45%, no evidence of physiologically significant pericardial effusion as determined by an ECHO, and no clinically significant ECG findings\n* No clinically significant pleural effusion\n* Baseline oxygen saturation \\>92% on room air at rest\n* creatinine: within age adjusted normal institutional limits (see table below) OR\n* creatinine clearance ≥60 mL\u002Fmin\u002F1.73 m2 (as estimated by Cockcroft Gault Equation) for subjects with creatinine levels above institutional normal.\n* Age (Years) Maximum Serum Creatinine (mg\u002FdL)\n\n  -≤5 0.8 5 \\\u003C age ≤ 10 1.0 \\>10 1.2\n* if these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy); A subject will not be excluded because of pancytopenia ≥ Grade 3 if it is due to disease, based on the results of bone marrow studies.\n* CNS Status\n* Subjects with ALL\n* Subjects with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy:\n* CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs;\n* CNS 2, defined as presence of \\\u003C 5\u002FµL WBCs in CSF and cytospin positive for blasts, or \\> 5\u002FµL WBCs but negative by Steinherz\u002FBleyer algorithm:\n\nCNS 2a: \\\u003C10\u002FµL RBCs; \\\u003C 5\u002FµL WBCs and cytospin positive for blasts; CNS 2b: ≥10\u002FµL RBCs; \\\u003C 5\u002FµL WBCs and cytospin positive for blasts; CNS 2c: ≥10\u002FµL RBCs; ≥5\u002FµL WBCs and cytospin positive for blasts but negative by Steinherz\u002FBleyer algorithm.\n\n* Subjects with lymphoma\n* Subjects must have no signs or symptoms of CNS disease or detectable evidence of CNS disease on MRI at the time of screening. Subjects who have previously been treated for CNS disease and who have the following CNS status will be eligible:\n* CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs;\n* CNS 2, defined as presence of \\\u003C 5\u002FµL WBCs in CSF and cytospin positive for blasts, or \\> 5\u002FµL WBCs but negative by Steinherz\u002FBleyer algorithm:\n* CNS 2a: \\\u003C 10\u002FµL RBCs; \\\u003C 5\u002FµL WBCs and cytospin positive for blasts;\n* CNS 2b: ≥ 10\u002FµL RBCs; \\\u003C 5\u002FµL WBCs and cytospin positive for blasts;\n* CNS 2c: ≥ 10\u002FµL RBCs; ≥ 5\u002FµL WBCs and cytospin positive for blasts but negative by Steinherz\u002FBleyer algorithm.\n* Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential)\n* Contraception Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four (4) months after receiving the preparative regimen.\n* Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous\u002Funknown effects on the fetus.\n* Ability to give informed consent. All subjects ≥ 18 years of age must be able to give informed consent. For subjects \\\u003C18 years old their legal authorized representative (LAR) (i.e. parent or guardian) must give informed consent. Pediatric subjects will be included in age appropriate discussion and verbal assent will be obtained for those \\> 7 years of age, when appropriate.\n\nExclusion Criteria:\n\nSubjects meeting any of the following criteria are not eligible for participation in the study:\n\n* Recurrent or refractory ALL limited to isolated testicular.\n* Subjects with radiologically-detected CNS lymphoma or CNS 3 disease (presence of ≥ 5\u002FµL WBCs in CSF and cytospin positive for blasts \\[in the absence of a traumatic lumbar puncture\\] and\u002For clinical signs of CNS leukemia).\n* Hyperleukocytosis (≥ 50,000 blasts\u002FµL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy.\n* History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years.\n* Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.\n* Ongoing infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive) as the immunosuppression contained in this study will pose unacceptable risk. A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and\u002For nucleic acid testing.\n* CNS disorder such as cerebrovascular ischemia\u002Fhemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement that in the judgment of the investigator may impair the ability to evaluate neurotoxicity.\n* History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment, or have cardiac atrial or cardiac ventricular lymphoma involvement.\n* Subjects receiving anticoagulation therapy.\n* Any medical condition that in the judgement of the principal investigator is likely to interfere with assessment of safety or efficacy of study treatment\n* History of severe immediate hypersensitivity reaction to any of the agents used in this study.\n* Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the conditioning lymphodepletion chemotherapy on the fetus or infant. Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential.\n* In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.\n* May not have primary immunodeficiency or history of systemic autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression\u002Fsystemic disease modifying agents within the last 2 years.","90 Years",{"count":342,"type":20},75,[23,96],"This is an open-label, single-arm, phase I clinical trial with dose escalation designed to investigate the safety, tolerability, and pharmacokinetic properties of Human CD19-CD22 Targeted T Cells Infusion. The primary objectives are to preliminarily assess the impact of Human CD19-CD22 Targeted T Cells Infusion in patients with relapsed\u002Frefractory B-cell acute lymphoblastic leukemia and to explore the appropriate dose and reinfusion schedule for phase II.\n\nEligible participants, including those with Central Nervous System Lymphoma, B Cell Lymphoma (BCL), Acute Lymphocytic Leukemia (ALL), Acute Lymphoblastic Leukemia (ALL), B Acute Lymphoblastic Leukemia (B-ALL), Refractory Non-Hodgkin Lymphoma, Refractory Chronic Lymphocytic Leukemia (CLL), Refractory B Acute Lymphoblastic Leukemia (B-ALL), Diffuse Large B Cell Lymphoma, Lymphoid Leukemia, and MRD-positive cases, can participate. Eligibility will be determined through a comprehensive assessment, including disease evaluations, a physical examination, Electrocardiograph, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), and blood tests. Prior to the infusion of CD19-CD22 CAR+ T cells, participants will undergo chemotherapy. After the infusion, participants will be closely monitored for potential side effects and the effectiveness of CD19-CD22 CAR+ T cells. Certain study procedures may be conducted during hospitalization.",[346,26,347,348,349,350,351],"Acute Lymphoblastic Leukemia, Adult B-Cell","Non-Hodgkin Lymphoma, B-cell","Diffuse Large B Cell Lymphoma","Central Nervous System Lymphoma","Lymphoma, Follicular","MCL",[349,353,354,355,348,356],"B Cell Lymphoma (BCL)","Acute Lymphocytic Leukemia (ALL)","Refractory Non-Hodgkin Lymphoma","MRD-positive cases","2025-08-05",{"date":359,"type":33},"2025-08-06",{"date":361,"type":33},"2024-07-10",{"date":363,"type":20},"2028-12-10",{"name":365,"class":40},"Essen Biotech",{"id":367,"slug":368,"hasResults":11,"nctId":369,"briefTitle":370,"officialTitle":371,"acronym":4,"eligibilityCriteria":372,"healthyVolunteers":11,"sex":16,"minAge":373,"maxAge":374,"enrollmentInfo":375,"targetDuration":4,"studyType":21,"phases":377,"briefSummary":378,"conditions":379,"keywords":380,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":385,"lastUpdatePostDateStruct":386,"startDateStruct":388,"completionDateStruct":390,"leadSponsor":392,"locationsCount":41},"100518747","phase-2-bortezomib-based-regimen-for-refractory-or-relapsed-acute-lymphoblastic-leukemia-100518747","NCT06034561","Bortezomib-based Regimen for Refractory or Relapsed Acute Lymphoblastic Leukemia","Bortezomib-based Regimen for Refractory or Relapsed Acute Lymphoblastic Leukemia in Adults","Inclusion Criteria:\n\n* Patients between 16 and 60 years-old with refractory or relapsed ALL (≥1% of anomalous blasts by flow cytometry in bone marrow or peripheral blood) after one or two lines of therapy, regardless of their phenotype or baseline genetic alteration;\n* Patients are eligible after allogeneic HSCT as long as patients are not actively being treated for graft-versus-host-disease (GvHD).\n\nExclusion Criteria:\n\n* Burkitt leukemia;\n* Prior myeloproliferative disease;\n* Drug allergies;\n* Eastern Cooperative Oncology Group (ECOG) scale \\>2;\n* Total bilirubin\\>2x upper limit of normal (ULN);\n* Transaminases\\>5x ULN;\n* Creatinine\\>2,5 mg\u002Fdl;\n* Active uncontrolled infection;\n* History of asparaginase-induced pancreatitis;\n* Prior exposure to bortezomib;\n* Heart failure New York Heart Association (NYHA) Class III or IV;\n* Patients with more than 400mg\u002Fm2 lifetime exposure of anthracycline;\n* Severe psychiatric disorder which prevents adequate compliance;\n* Refusal to participate in the study.","16 Years","60 Years",{"count":376,"type":20},50,[96],"This is a interventional phase II study aiming to examine the complete response rate of a bortezomib-based salvage regimen in adults with refractory or relapsed acute lymphoblastic leukemia (ALL), seeking to compare outcomes with the available literature and with our historical data on relapsed\u002Frefractory ALL.",[26,61],[291,381,382,383,384],"Bortezomib","Salvage therapy","Bridge therapy","Response rate","2025-05-13",{"date":387,"type":33},"2025-05-16",{"date":389,"type":33},"2024-04-01",{"date":391,"type":20},"2029-08",{"name":393,"class":40},"Instituto do Cancer do Estado de São Paulo",{"id":395,"slug":396,"hasResults":11,"nctId":397,"briefTitle":398,"officialTitle":399,"acronym":4,"eligibilityCriteria":400,"healthyVolunteers":11,"sex":16,"minAge":139,"maxAge":4,"enrollmentInfo":401,"targetDuration":4,"studyType":21,"phases":403,"briefSummary":404,"conditions":405,"keywords":406,"overallStatus":322,"whyStopped":4,"lastUpdateSubmitDate":409,"lastUpdatePostDateStruct":410,"startDateStruct":412,"completionDateStruct":414,"leadSponsor":416,"locationsCount":41},"100565349","phase-1-clinical-research-of-cd19-targeted-car-t-cell-in-relapsed-refractory-b-all-100565349","NCT06641024","Clinical Research of CD19 Targeted CAR-T Cell in Relapsed\u002F Refractory B-ALL","Phase I Clinical Study of CD19-targeting Chimeric Antigen Receptor T Lymphocyte (MC-1-50) for the Treatment of Relapsed\u002FRefractory CD19-positive B-cell Acute Lymphoblastic Leukemia (B-ALL)","Inclusion Criteria:\n\n1. The patient or their guardian agrees to participate in this clinical trial and sign the ICF, indicating their understanding of the purpose and procedures of this clinical trial and willingness to participate in the study;\n2. Age ≥ 18 years old (including threshold), gender not limited;\n3. Diagnosed with B-cell acute lymphoblastic leukemia and meeting one of the following conditions:\n\n   1. Refractory B-ALL: Early refractory patients who have not achieved complete remission of bone marrow after two courses of first-line systemic therapy upon initial diagnosis;\n   2. Relapsed B-ALL:\n\n      ① Early relapsed after complete remission (\\< 12 months);\n\n      ② Late relapsed after complete remission (≥ 12 months) requires systemic therapy again, but if complete remission is not achieved or early treatment response is poor;\n\n      ③ Having experienced 2 or more times bone marrow relapse;\n\n      ④ Relapsed after allogeneic hematopoietic stem cell transplantation;\n   3. Individuals with Philadelphia chromosome positive (Ph+) disease are eligible if they have relapsed\u002Frefractory disease despite treatment with at least 2 different tyrosine kinase inhibitors (TKIs); (Note: Except for those who are intolerant to TKI therapy, or have T315i mutations);\n4. Flow cytometry confirms the expression of CD19 in leukemia cells in the bone marrow. In individuals previously treated with targeted CD19 antibodies (such as blinatumomab), the proportion of CD19 positive cells in leukemia cells must be ≥ 90%;\n5. Morphological disease in the bone marrow (≥ 5% blasts);\n6. ECOG score 0-1;\n7. Expected survival time of more than 12 weeks;\n8. Adequate renal, hepatic, pulmonary and cardiac function defined as:\n\n   1. Cardiac function: Echocardiography indicates left ventricular ejection fraction ≥ 50%;\n   2. Renal function: serum creatinine ≤ 2.0 × ULN, or creatinine clearance rate ≥ 60ml\u002Fmin (Cockcroft Gault formula);\n   3. Hepatic function: ALT and AST ≤ 3.0 × ULN (may be relaxed to ≤ 5.0 × ULN in cases of combined liver infiltration);\n   4. Total bilirubin ≤ 2.0 × ULN (Gilbert syndrome requires total bilirubin ≤ 3.0 × ULN);\n   5. Pulmonary function: Blood oxygen saturation is ≥ 92% in non oxygen state.\n9. No serious mental disorders;\n10. Meet standards for apheresis or venous blood collection, and no other cell collection contraindications;\n11. Women of childbearing age who have a negative blood pregnancy test and all subjects agree to use reliable and effective contraceptive methods (excluding safe period contraception) for contraception within one year after receiving MC-1-50 cell infusion from the time of signing the informed consent form. Including but not limited to: abstinence, implantable progestogen contraceptives that can inhibit ovulation; Intrauterine device (IUD); Intrauterine hormone release system; Spouse vasectomy; Compound hormone contraceptives that can inhibit ovulation (oral, vaginal, and transdermal); Progesterone contraceptives (oral or injectable) that can inhibit ovulation; When male subjects have sex with fertile women, they must agree to use barrier contraception (such as condom plus spermicidal foam\u002Fgel\u002Ffilm\u002Femulsion\u002Fsuppository). At the same time, participants should commit not to donate eggs (oocytes, oocytes) or sperm for assisted reproduction within one year after cell infusion.\n\nExclusion Criteria:\n\n1. Isolated extramedullary disease;\n2. Central nervous system abnormalities: defined as CNS-2 and 3 according to NCCN guidelines (note: CNS-2 and 3 can be screened, but must be treated and recovered to CNS-1 before lymphodepleting chemotherapy and infusion);\n3. Transformation of chronic myeloid leukemia to acute biphenotypic leukemia;\n4. Individuals who have received CAR-T therapy or other gene modified cell therapies;\n5. Prior to apheresis, the following anti-tumor treatments have been received: chemotherapy, targeted therapy, and other drug treatments within 14 days or at least 5 half lives (whichever is shorter); Received radiation therapy within 14 days;\n6. HBsAg or HBcAb positive and HBV DNA is greater than the normal range; HCV antibody is positive and HCV RNA greater than the normal range; HIV antibody positive; syphilis positive; CMV DNA positive;HBsAg or HBcAb positive and HBV DNA is greater than the normal range; HCV antibody is positive and HCV RNA greater than the normal range; HIV antibody positive; syphilis positive;\n7. Suffered from any of the following heart diseases:\n\n   1. New York Heart Association (NYHA) stage III or IV congestive heart failure;\n   2. Within the 6 months prior to enrollment, there has been a myocardial infarction, or a coronary artery bypass grafting (CABG) or stent implantation surgery has been performed;\n   3. History of ventricular arrhythmias requiring treatment or unexplained syncope (excluding cases caused by vasovagal or dehydration);\n   4. History of severe non-ischemic cardiomyopathy;\n8. Uncontrollable infection in the 2 weeks before enrollment;\n9. Acute grade 2-4 graft-versus-host disease (GVHD) or moderate to severe chronic GVHD within the first 4 weeks of enrollment;\n10. If a cerebrovascular accident or seizure occurs within the first 6 months of enrollment;\n11. Active autoimmune diseases;\n12. Deep vein or deep artery embolism event within the past 6 months prior to enrollment;\n13. Poor control of hypertension during screening is defined as systolic blood pressure ≥ 160mmHg and\u002For diastolic blood pressure ≥ 100mmHg (blood pressure values are measured based on the average of three readings taken at least 2 minutes apart. Patients with blood pressure ≥ 160\u002F100mmHg at the initial screening can receive antihypertensive treatment, and if good control is achieved after treatment and blood pressure\\<160\u002F100mmHg, enrollment can be performed);\n14. History of malignancy other than fully treated cervical carcinoma in situ, basal cell or squamous cell carcinoma of the skin, local prostate cancer after radical surgery, and ductal carcinoma in situ of the breast after radical surgery;\n15. (attenuated) Live vaccine ≤ 4 weeks prior to enrollment;\n16. Have participated in other clinical trials within one month or five drug half lives (whichever is shorter) before enrollment;\n17. Women who are pregnant or breastfeeding, and male or female subjects who plan to have children within 1 year after receiving MC-1-50 cell infusion;\n18. Other situations considered by the investigator to be unsuitable to participate in the study.",{"count":402,"type":20},24,[23],"This is a single-arm, open-label, dose-escalation phase I clinical study to explore the safety, tolerability, and cytokinetic characteristics of MC-1-50 cell formulation, and to preliminarily observe the efficacy of MC-1-50 cell formulation in subjects with relapsed\u002Frefractory CD19-positive B Cell Acute Lymphoblastic Leukemia.",[26,100],[407,408],"B-ALL","CAR-T","2024-10-11",{"date":411,"type":33},"2024-10-15",{"date":413,"type":20},"2024-11-01",{"date":415,"type":20},"2039-11-01",{"name":417,"class":418},"Chongqing Precision Biotech Co., Ltd","INDUSTRY",{"id":420,"slug":421,"hasResults":11,"nctId":422,"briefTitle":423,"officialTitle":424,"acronym":4,"eligibilityCriteria":425,"healthyVolunteers":11,"sex":16,"minAge":139,"maxAge":4,"enrollmentInfo":426,"targetDuration":4,"studyType":21,"phases":427,"briefSummary":428,"conditions":429,"keywords":430,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":432,"lastUpdatePostDateStruct":433,"startDateStruct":435,"completionDateStruct":437,"leadSponsor":439,"locationsCount":441},"100550340","phase-1-cd19cd22-car-t-cells-in-adults-with-rr-all-or-nhl-100550340","NCT06445803","CD19\u002FCD22 CAR-T Cells in Adults With R\u002FR ALL or NHL","A Preliminary Study to Evaluate the Safety, Tolerability, Preliminary Efficacy and Pharmacokinetic Profile of KQ-2002 (CD19\u002FCD22 CAR-T) in Adults With Recurrent or Refractory Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma","Inclusion Criteria:\n\n* Male or female,≥18 years old;\n* Histologically confirmed diagnosis of B-ALL or B-NHL(meeting one of the following conditions):\n\n(B-NHL)\n\n1. Second or greater relapse (CD20 regimens must be included) OR\n2. Refractory to first-line chemotherapy or relapse within 1 year OR\n3. Relapse within 1 year of auto-HSCT.\n4. With measurable or evaluable lesions（Dose expansion cohort） (B-ALL)\n\na. Relapse within 12 months of complete remission on first treatment OR b. Relapse after second-line treatment OR c. Relapse after auto HST OR d. Failure to achieve CR\u002FCRi at the end of induction therapy OR e. Ph+ ALL intolerance to TKI or refractory or relapse after treatment with at least two and more TKIs.\n\n* ECOG 0\\~2\n* Estimated survival time ≥ 12 weeks;\n* Main tissues and organs function well.\n\nExclusion Criteria:\n\n* Subjects will be excluded related to the following prior therapy criteria:Prior treatment with bendamustine-containing or fludarabine;Anti-T-cell monoclonal antibody, donor lymphocyte infusion, and CNS radiotherapy within 8 weeks; Chemotherapy, lenalidomide, bortezomib within 2 weeks; vincristine within 1 week; glucocorticoids (prednisone ≥7.5 mg\u002Fd or equivalent) within 72 h\n* Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening), or any uncontrolled infection at screening\n* Uncontrolled, symptomatic, intercurrent illness including but not limited to angina pectoris, cerebrovascular accident or transient ischemia (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), New York Heart Association (NYHA) classification of ≥ Class III congestive heart failure, severe arrhythmia poorly controlled by medications, hepatic, renal, or metabolic disorders, and hypertension that is uncontrolled by standard therapy；\n* active bleeding, or venous thromboembolic event\n* Autoimmune diseases (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, etc.) that result in end-organ damage or require systemic application of immunosuppressive drugs\n* Central nervous system (CNS) disease or symptoms of CNS involvement\n* Pregnant or nursing (lactating) women\n* Presence of Grade 2 or above non-hematologic toxicity , alopecia and grade 2 neuropathy excluded\n* Any Iinappropriate conditions in the opinion of the PI .",{"count":141,"type":20},[23],"This study examines the safety, tolerability and preliminary efficacy of anti-CD19 \u002FCD22 CAR T cells (KQ-2002)manufactured on-site in adults with relapsed or refractory CD19+ B cell acute lymphoblastic leukemia or CD19+ B cell non Hodgkin lymphoma.",[26,61,225,224],[431],"CAR-T therapy","2024-06-01",{"date":434,"type":33},"2024-06-06",{"date":436,"type":33},"2024-05-31",{"date":438,"type":20},"2026-12",{"name":440,"class":40},"Rong Tao",2,{"id":443,"slug":444,"hasResults":11,"nctId":445,"briefTitle":446,"officialTitle":446,"acronym":447,"eligibilityCriteria":448,"healthyVolunteers":11,"sex":16,"minAge":49,"maxAge":449,"enrollmentInfo":450,"targetDuration":4,"studyType":21,"phases":451,"briefSummary":452,"conditions":453,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":455,"lastUpdatePostDateStruct":456,"startDateStruct":458,"completionDateStruct":460,"leadSponsor":462,"locationsCount":464},"100463123","phase-1-combination-of-an-anti-pd1-antibody-with-tisagenlecleucel-reinfusion-in-children-adolescents-and-young-adults-with-acute-lymphoblastic-leukemia-after-loss-of-persistence-100463123","NCT05310591","Combination of an Anti-PD1 Antibody With Tisagenlecleucel Reinfusion in Children, Adolescents and Young Adults With Acute Lymphoblastic Leukemia After Loss of Persistence","CAPTiRALL","Inclusion Criteria:\n\n* Patients aged from 1 to 25 years (pediatric and young adults) with a history of CD19+ relapsed or refractory B-ALL (any relapse after HSCT, 2nd relapse or later, refractory ALL).\n* Patient must have a second tisagenlecleucel (Kymriah ®) product available\n* Cohort 1: previously treated by tisagenlecleucel (Kymriah ®), and who present an early loss of B-cell aplasia defined by blood B lymphocytes \\\u003C 10 \u002Fmm3 and\u002F or \\\u003C 3% of total lymphocytes (\\\u003C 6 months after infusion) while still being in CR with undetectable MRD\n* Cohort 2: previously treated by tisagenlecleucel (Kymriah ®), who present a loss of B-cell aplasia defined by blood B lymphocytes \\\u003C 10 \u002Fmm3 and\u002F or \\\u003C 3% of total lymphocytes and a CD19+ ALL detectable disease in the marrow and\u002For Blood\n* Life expectancy \\> 12 weeks.\n* Karnofsky (age \\> 16) Lansky (age \\\u003C 16) \\> 70 at screening.\n* No organ dysfunction\n* Who have signed an informed consent\n* Affiliation to social security or any health insurance (as a beneficiary or assignee)\n\nExclusion Criteria:\n\n* Patient has received intervening therapy for leukemia after first tisagenlecleucel infusion (chemotherapy, anti leukemic immunotherapy, ITK, allogeneic HSCT).\n* Patient has an active autoimmune disease requiring systemic treatment within the past 2 years.\n* Patient has known history of, or any evidence of active, non-infectious pneumonitis.\n* Patient has a history of non-infectious pneumonitis that required steroid or has current pneumonitis.\n* Had receive prior therapy with an anti-PD1, Anti- PDL1 or anti-PDL2 agent.\n* Patient has hypersensivity to pembrolizumab\u002F nivolumab or one of its excipients\n* Patient has received a live vaccine injection within 45 days of planned start of study therapy.\n* Patients with concomitant genetic syndromes associated with bone marrow failure states: such as patients with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Patients with Down syndrome will not be excluded.\n* Patients with Burkitt's lymphoma\u002Fleukemia\n* Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease.\n* Prior treatment with any gene therapy product except first tisagenlecleucel (Kymriah ®) injection.\n* Prior treatment with any anti-CD19\u002Fanti-CD3 therapy, or any other anti-CD19 therapy, except for patients pre-treated with blinatumomab and\u002For tisagenlecleucel (Kymriah®)\n* Prior anti-cancer monoclonal antibody within 4 weeks before starting the study.\n* Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade1 or at baseline) from adverse events due to a previously administered agent.\n* Active or latent hepatitis B or active hepatitis C (test within 8 weeks of Screening), or any uncontrolled infection at Screening.\n* Human immunodeficiency virus (HIV) positive test within 8 weeks of Screening.\n* Presence of grade 2 to 4 acute or extensive chronic GVHD.\n* Active CNS involvement by malignancy, defined as CNS-3 per NCCN guidelines. Note: Patients with history of CNS disease that has been effectively treated will be eligible.\n* Uncontrolled acute life threatening bacterial, viral or fungal infection at Screening.\n* Previous or concurrent malignancy with the following exceptions:\n\n  * Adequately treated basal cell or squamous cell carcinoma\n  * in situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to the study.\n  * A primary malignancy completely resected and in CR for ≥ 5 years\n* Pregnant or lactating women (female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion)\n* Patient with hypersensivity to Fludarabine and\u002For cyclophosphamide and\u002For tisagenlecleucel and\u002For nivolumab or one of their excipients.","25 Years",{"count":249,"type":20},[23,96],"Tisagenlecleucel (CTL019) is an anti-CD19 autologous Chimeric Antigen Receptor (CAR) T-cell therapy, which has shown dramatic early results in advanced ALLs. Early loss of B-cell aplasia (recovery of B-cells in marrow\u002F peripheral blood within 6 months after infusion), a marker of the loss or non-functionality of the CAR T-cells, is associated to a very high risk of relapse. A reinfusion of CTL019, even after Fludarabine-Cyclophosphamide reconditioning, frequently fails to induce further expansion as observed in UPENN studies and in the Robert Debré Hospital experience.\n\nNon-persistence of CAR T-cells may be due to immune- mediated rejection or environment-mediated suppression of their growth. Evidence for increased PD-1 expression in CAR T-cells between infusion and peak expansion has been demonstrated in clinical samples.\n\nPreclinical data and few clinical data support a role of PD- 1-PD-L1 blockade in improving the effectiveness of CAR T-cell therapy.\n\nThe objectives of this phase I\u002FII study is to determine the safety, efficacy and feasibility of Nivolumab (Opdivo®)- an anti-PD1 treatment- combined to tisagenlecleucel in a cohort of relapsed or refractory B-ALL patients, aged 1-25 years old, previously treated by tisagenlecleucel (Kymriah®), with a demonstrated early loss of B-cell aplasia (within 6 months), a surrogate marker of the loss of CAR T-cells or their non- functionality.\n\nMore specifically, the main objectives are:\n\n• In cohort 1 that includes patients with a MRD negative disease status combined to an early loss (within 6 months) of B-cell aplasia :\n\nTo determine the optimal starting time of Nivolumab (Opdivo®) in terms of safety and efficacy among 4 candidate time points (day 14, day 11, day 5, and day - 1).\n\n• In cohort 2 that includes relapsed patients with an early loss (within 6 months) of B-cell aplasia :\n\nTo estimate the feasibility in terms of safety and efficacy of a very early start of nivolumab (day-1), prior to the reinfusion of tisagenlecleucel",[454,26],"B Acute Lymphoblastic Leukemia","2024-05-26",{"date":457,"type":33},"2024-05-29",{"date":459,"type":33},"2023-03-15",{"date":461,"type":20},"2027-03",{"name":463,"class":40},"Assistance Publique - Hôpitaux de Paris",13,{"id":466,"slug":467,"hasResults":11,"nctId":468,"briefTitle":469,"officialTitle":470,"acronym":4,"eligibilityCriteria":471,"healthyVolunteers":11,"sex":16,"minAge":139,"maxAge":92,"enrollmentInfo":472,"targetDuration":4,"studyType":21,"phases":474,"briefSummary":475,"conditions":476,"keywords":480,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":486,"lastUpdatePostDateStruct":487,"startDateStruct":489,"completionDateStruct":491,"leadSponsor":493,"locationsCount":41},"100408853","early-phase-1-car-t-cells-combined-with-dasatinib-for-patients-with-relapsed-andor-refractory-b-cell-hematological-malignancies-100408853","NCT04603872","CAR-T Cells Combined With Dasatinib for Patients With Relapsed and\u002For Refractory B-cell Hematological Malignancies","Clinical Trial for the Safety and Efficacy of CD19\u002FBCMA-targeted CAR-T Cells Combined With Dasatinib for Patients With Relapsed and\u002For Refractory B-cell Acute Lymphoblastic Leukemia, B-cell Non-Hodgkin's Lymphoma and Multiple Myeloma","Inclusion Criteria:\n\n1. Histologically confirmed diagnosis of CD19+ ALL, CD19+ NHL, or BCMA+ MM per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines (2020.v2);\n2. Relapsed or refractory B cell hematological malignancies (meeting one of the following conditions):\n\n   1. CR not achieved after standardized chemotherapy;\n   2. CR achieved following the first induction, but CR duration is less than 12 months;\n   3. Ineffectively after first or multiple remedial treatments;\n   4. 2 or more relapses;\n   5. Relapse after hematopoietic stem cell transplantation;\n   6. Extramedullary leisions which were ineffective to radiotherapy or chemotherapy;\n3. Total bilirubin ≤ 51 umol\u002FL, ALT and AST ≤ 3 times of upper limit ofnormal, creatinine ≤ 176.8 umol\u002FL;\n4. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;\n5. No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;\n6. Estimated survival time ≥ 12 weeks;\n7. ECOG performance status 0 to 2;\n8. Women of childbearing age had negative pregnancy test during screening period and before administration, and agreed to take effective contraceptive measures at least one year after infusion.\n9. Patients volunteer to participate in the study and sign the informed consent.\n\nExclusion Criteria:\n\nSubjects with any of the following exclusion criteria were not eligible for this trial:\n\n1. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases;\n2. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;\n3. Pregnant (or lactating) women;\n4. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);\n5. Active infection of hepatitis B virus or hepatitis C virus;\n6. Concurrent therapy with systemic steroids within 2 weeks prior toscreening, except for the patients recently or currently receiving in haledsteroids;\n7. Previously treated with any CAR-T cell product or other genetically-modified T cell therapies;\n8. Creatinine \\>2.5mg\u002Fdl, or ALT \u002F AST \\> 3 times of normal amounts, or bilirubin \\>2.0 mg\u002Fdl;\n9. Other uncontrolled diseases that were not suitable for this trial;\n10. Patients with HIV infection;\n11. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.",{"count":473,"type":20},120,[312],"A Study of CD19\u002FBCMA-targeted CAR-T Cells Combined With Dasatinib for Patients With Relapsed and\u002For Refractory B-cell Acute Lymphoblastic Leukemia, B-cell Non-Hodgkin's Lymphoma and Multiple Myeloma.",[477,478,26,479,315,316],"Multiple Myeloma in Relapse","Multiple Myeloma, Refractory","Acute Lymphocytic Leukaemia Refractory",[481,482,483,484,485],"Acute Lymphoblastic Leukemia","Non-Hodgkin's Lymphoma","Multiple Myeloma","CAR T-cell therapy","Dasatinib","2020-10-27",{"date":488,"type":33},"2020-10-28",{"date":490,"type":20},"2020-11-01",{"date":492,"type":20},"2026-11-01",{"name":494,"class":40},"Zhejiang University"]