[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Shanghai First Song Biotechnology Co., LTD\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":59},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,41],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":29,"lastUpdatePostDateStruct":30,"startDateStruct":33,"completionDateStruct":35,"leadSponsor":37,"locationsCount":40},"100557016","early-phase-1-anti-cd19-car-t-cells-in-subjects-with-relapsedrefractory-b-cell-malignancies-100557016",false,"NCT06532630","Anti-CD19-CAR-T Cells in Subjects With Relapsed\u002FRefractory B Cell Malignancies","An Exploratory Clinical Study Evaluating the Safety and Efficacy of Anti-CD19-CAR-T Cell Therapy in Subjects With Relapsed\u002FRefractory B Cell Malignancies","Inclusion Criteria:\n\nSubjects must meet all of the following criteria for inclusion in the study:\n\n1. Patient able to provide written informed consent; parent or guardian of minor patient able to provide written informed consent; ability and willingness to adhere to the study visit schedule and all protocol requirements.\n2. 14 - 70 years old.\n3. Relapsed\u002Frefractory disease after standard treatment (including allogeneic\u002Fautologous hematopoietic stem cell transplantation) and not eligible for other treatment options such as a second hematopoietic stem cell transplant.\n\n   A. Relapsed\u002Frefractory B-cell acute lymphoblastic leukemia (ALL) is defined as one of the following:\n   * Primary refractory disease.\n   * Relapsed within 12 months after first remission.\n   * Relapsed or refractory after two or more lines of systemic therapy.\n   * Relapsed or refractory post allogeneic SCT. i. more than 100 days from the transplantation at the time of enrollment. ii. not receiving immunosuppressive drugs for 4 weeks prior to enrollment (≤5 mg prednisone or equivalent is allowed).\n\n   B. Ph+ B-cell ALL are eligible if they are intolerant or ineligible for tyrosine kinase inhibitor (TKI) therapy or have relapse\u002Frefractory disease after at least two different TKI treatments.\n\n   C. Relapsed\u002Frefractory B-cell non-Hodgkin lymphoma (NHL) is defined as one of the following:\n   1. No response to first-line therapy (primary refractory disease, excluding subjects intolerant to first-line therapy):\n\n      * PD is the best response after first-line therapy.\n      * Best response after at least 4 cycles of first-line therapy (e.g., 4 cycles of R-CHOP) is stable disease (SD), with rapid progression in 6 months.\n   2. No response to second or subsequent lines of therapy:\n\n      * PD is the best response to last regimen.\n      * Best response after at least 2 cycles of the last-line therapy is SD, with rapid progression in 6 months.\n   3. Refractory post-autologous stem cell transplant (ASCT):\n\n      * Disease progression or relapse within 12 months (relapse must be biopsy-proven).\n      * If salvage therapy is given post-ASCT, the subject must have had no response to or relapsed after the last line of therapy\n      * Relapsed or refractory after two or more lines of systemic therapy.\n4. Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening\n5. Relapsed\u002Frefractory NHL as one of the following subtypes:\n\n   A. DLBCL-NOS B. Primary mediastinal large B-cell lymphoma (PMBCL) C. Transformed follicular lymphoma (TFL) following prior chemotherapy for follicular lymphoma and subsequent transformation to DLBCL with refractory disease.\n\n   D. Mantle cell lymphoma E. High-grade B-cell lymphoma F. CLL\u002FSLL\n6. ECOG performance status ≤2.\n7. Life expectancy ≥ 12 weeks.\n8. Adequate venous access (for apheresis) and no other contraindications for blood cell separation.\n9. Subjects must meet the following laboratory criteria at screening, and they should not have received any growth factors within the 7 days prior to the hematologic assessment:\n\n   A. Absolute neutrophil count ≥1.0×10\\^9\u002FL. For subjects with ALL, specific criteria will be determined by the investigator.\n\n   B. Hemoglobin ≥60 g\u002FL (without RBC transfusion within 14 days). C. Platelets ≥50×10\\^9\u002FL. For subjects with ALL, specific criteria will be determined by the investigator.\n\n   D. Absolute lymphocyte count (ALC) ≥0.5×10\\^9\u002FL. If the total lymphocyte count is insufficient with a high proportion of T cells, the investigator may discuss with the sponsor.\n\n   E. Total bilirubin \\\u003C1.5×ULN; if liver involved, total bilirubin \\\u003C3.0×ULN is allowed.\n\n   F. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN; if liver involved, ALT\u002FAST ≤5×ULN is allowed.\n\n   G. Creatinine \\\u003C1.5×ULN and estimated creatinine clearance ≥60 mL\u002Fmin.\n10. Cardiac ejection fraction (EF) ≥45% with no clinically significant findings on electrocardiogram.\n11. Baseline oxygen saturation \\>92% on room air.\n12. Women of childbearing potential must have a negative serum or urine pregnancy test (women who have undergone surgical sterilization or have been postmenopausal for at least 2 years are not considered of childbearing potential).\n\nExclusion Criteria:\n\nIf patients meet any of the following conditions, they cannot participate in this trial:\n\n1. Central nervous system (CNS) involvement in ALL and clinically significant neurological changes (CNS-2 and CNS-3):\n\n   1. CNS-3, defined as detectable tumor cells in cerebrospinal fluid (CSF) with ≥ 5 white blood cells (WBCs) \u002Fmm3.\n   2. CNS-2, defined as detectable tumor cells in CSF with \\\u003C5 WBCs \u002Fmm3. Note: Subjects with CNS-1 (no detectable tumor cells in CSF) or CNS-2 without evidence of clinically significant neurological changes are eligible for this study.\n2. CNS lymphoma confirmed by MRI; active CNS DLBL unless CNS involvement has been effectively treated (i.e., asymptomatic) and a local treatment interval of \\> 4 weeks prior to enrollment.\n3. Active CNS diseases such as epilepsy, cerebrovascular ischemia\u002Fhemorrhage, dementia, cerebellar disorders, or any autoimmune diseases involving the central nervous system.\n4. Any malignancies other than CD19+ malignancies.\n5. Clinically significant heart disease or arrhythmias not controlled by medication.\n6. Ongoing or suspected fungal, bacterial, viral, or other infections that are uncontrolled or require intravenous antibiotic therapy; simple urinary tract infections and simple bacterial pharyngitis are allowed.\n7. Hepatitis B (positive for hepatitis B surface antigen and hepatitis B DNA \\>1000 copies\u002FmL) and hepatitis C (positive for hepatitis C antibodies); syphilis, human immunodeficiency virus (HIV) infection.\n8. Presence of any indwelling or drainage catheter (e.g., percutaneous nephrostomy, indwelling Foley catheter, biliary drainage catheter, pleural\u002Fperitoneal\u002Fpericardial drainage catheter); the use of dedicated central venous access devices such as Port-A-Cath® or Hickman® catheters is allowed.\n9. Prior use of the following:\n\n   1. CD19-targeted therapy.\n   2. Chlorambucil or bendamustine within 3 months before enrollment, or PEG-asparaginase within 3 weeks before enrollment.\n   3. live vaccines within 4 weeks before enrollment.\n   4. Donor lymphocyte infusions (DLI) within 4 weeks before enrollment.\n   5. Medications for graft-versus-host disease (GVHD) treatment within 4 weeks before enrollment, such as calcineurin inhibitors, methotrexate, mycophenolate, rapamycin, or siltuximab, or use of immunosuppressive antibodies (anti-CD20, anti-tumor necrosis factor, anti-interleukin 6, or anti-interleukin 6 receptor) within 4 weeks before enrollment.\n   6. Immunostimulatory or immunosuppressive therapy within 4 weeks before enrollment, including interferon-α, interferon-β, IL-2, lenalidomide, efalizumab, alemtuzumab, tocilizumab, cyclosporine, or thalidomide.\n   7. Anti-PD-1\u002Fanti-PD-L1 therapy within 4 weeks before enrollment.\n   8. Systemic cytotoxic chemotherapy within 14 days before enrollment, including daily or weekly low-dose maintenance chemotherapy (e.g., cyclophosphamide, ifosfamide, bendamustine, chlorambucil, melphalan, or vincristine).\n   9. Long-acting growth factors (e.g., pegfilgrastim) within 14 days before apheresis or short-acting growth factors within 5 days before apheresis or mobilization agents (e.g., filgrastim\u002Fpegfilgrastim, plerixafor) within 5 days before apheresis.\n   10. Radiation therapy within 14 days before enrollment.\n   11. Pharmacological doses of corticosteroids (\\>5 mg\u002Fday prednisone or equivalent) or other immunosuppressive drugs within 7 days before enrollment.\n   12. Venetoclax (BCL-2 inhibitor) within 4 days before apheresis.\n   13. Short-acting targeted therapy (e.g., tyrosine kinase inhibitors) within 72 hours before apheresis.\n   14. Idelalisib (oral PI3Kδ inhibitor) within 2 days before apheresis.\n   15. Lenalidomide within 1 day before enrollment.\n10. ≥ Grade 2 graft-versus-host disease (GVHD) per the CIBMTR grading system or requiring systemic corticosteroid treatment exceeding physiological doses.\n11. A history of autoimmune diseases in the past 2 years, such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, leading to end-organ damage or requiring systemic immunosuppression or disease-modifying agents.\n12. A history of heart attack, cardiac catheterization or stent implantation, unstable angina, or other clinically significant heart diseases within 12 months before enrollment.\n13. A history of genetic syndrome with bone marrow failure, such as Fanconi anemia, Kostmann syndrome, Schwachman-Diamond syndrome, etc.\n14. Symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months before enrollment. Subjects need to be on prophylactic anticoagulation.\n15. A history of or currently having other malignant tumors (excluding skin basal cell carcinoma, breast\u002Fcervical carcinoma in situ, and other malignant tumors that have not been treated in the past five years but are effectively controlled).\n16. Use of other investigational medicinal products within 30 days before screening.\n17. Pregnant, planning to become pregnant, or breastfeeding in reproductive-aged women. Women who have undergone surgical sterilization or have been postmenopausal for at least 2 years are not considered to be of reproductive potential.\n18. Male and female subjects unwilling to practice contraception from the time of agreeing to treatment until 12 months after completion of conditioning chemotherapy or CAR-T infusion.\n19. Any past medical history that may interfere with the safety of the study treatment or the evaluation of efficacy.\n20. Based on the investigator's judgment, subjects are unlikely to complete all the study visits or procedures required by the protocol.\n21. Previous use of any CAR-T cell product or other gene-modified T cell therapy.","ALL","14 Years","70 Years",{"count":20,"type":21},9,"ESTIMATED","INTERVENTIONAL",[24],"EARLY_PHASE1","This is a single-center, single-arm, open-label, exploratory study to determine the safety, tolerability, feasibility, and preliminary anti-tumor activity of anti-CD19-CAR-T cells in subjects with relapsed\u002Frefractory (r\u002Fr) B-cell malignancies.\n\nThis study plans to enroll patients with relapsed\u002Frefractory CD19-positive B-cell malignancies, who will receive a single infusion of anti-CD19-CAR-T cells after screening, PBMC collection, and lymphodepleting chemotherapy.",[27],"B-Cell Malignancy","RECRUITING","2025-02-25",{"date":31,"type":32},"2025-02-28","ACTUAL",{"date":34,"type":32},"2023-08-24",{"date":36,"type":21},"2026-09-01",{"name":38,"class":39},"Shanghai First Song Biotechnology Co., LTD","INDUSTRY",1,{"id":42,"slug":43,"hasResults":11,"nctId":44,"briefTitle":45,"officialTitle":46,"acronym":4,"eligibilityCriteria":47,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":48,"targetDuration":4,"studyType":22,"phases":49,"briefSummary":50,"conditions":51,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":53,"lastUpdatePostDateStruct":54,"startDateStruct":56,"completionDateStruct":57,"leadSponsor":58,"locationsCount":40},"100557017","early-phase-1-safety-and-efficacy-of-anti-cd20cd30-car-t-cells-in-subjects-with-relapsedrefractory-lymphoma-100557017","NCT06532643","Safety and Efficacy of Anti-CD20\u002FCD30 CAR-T Cells in Subjects with Relapsed\u002FRefractory Lymphoma","An Exploratory Clinical Study of Autologous Anti-CD20\u002FCD30 Chimeric Antigen Receptor T Cells (anti-CD20\u002FCD30 CAR-T Cells) in Subjects with Relapsed\u002FRefractory Lymphoma","Inclusion Criteria\n\n* Patients must meet all of the following criteria to be eligible for the study:\n\n  1. Voluntarily participate in the clinical study. The individual or the legal guardian fully understands the study, sign the informed consent form (ICF), and is willing and able to follow and complete all trial procedures.\n  2. Age ≥ 14 years and \\\u003C 70 years.\n  3. Subjects with refractory or relapsed disease after current standard treatments (including allogeneic or autologous hematopoietic stem cell transplantation) who are not suitable for other treatment options, such as a second stem cell transplant. The definitions of relapsed\u002Frefractory lymphoma include one of the following situations:\n\n     1. No response to first-line treatment (primary refractory disease, excluding participants intolerant to first-line treatments).\n\n        * Disease progression (PD) as assessed after first-line treatment.\n        * Best efficacy of first-line treatment (e.g., 4 cycles of RCHOP) as stable disease (SD), with the duration of SD not exceeding 6 months after the last dose.\n     2. No response to second-line or more treatments.\n\n        * PD being the best response to the most recent treatment.\n        * Best efficacy of the last line of treatment as SD after at least 2 cycles, with the duration of SD not exceeding 6 months after the last dose.\n     3. Refractory after autologous stem cell transplant (ASCT).\n\n        * Disease progression or relapse ≤ 12 months post-ASCT (relapsed patients must have biopsy-proven relapse).\n        * If salvage treatment is administered after ASCT, the subjects must not have had a response or relapse after the last line of treatment.\n        * Relapsed or refractory disease after two or more lines of systemic treatment.\n  4. Lymphoma patients must have target antigens meeting the following criteria:\n\n     1. CD20\u002FCD30 double-positive expressing lymphoma.\n     2. Relapse after receiving anti-CD19-CAR-T cell therapy, with CD20 positive lymphoma.\n     3. CD20 positive lymphoma that has not previously received anti-CD19-CAR-T cell therapy.\n     4. CD30 positive Hodgkin lymphoma.\n  5. Subtypes of lymphoma included for enrollment are as follows:\n\n     1. DLBCL-NOS (diffuse large B-cell Lymphoma, not otherwise specified)\n     2. Primary mediastinal B-cell lymphoma (PMBCL)\n     3. Transformed follicular lymphoma (TFL), previously treated for follicular lymphoma and then transformed to refractory DLBCL\n     4. Mantle cell lymphoma\n     5. High-grade B-cell lymphoma\n     6. Chronic lymphocytic leukemia\u002Fsmall lymphocytic lymphoma (CLL\u002FSLL)\n     7. Hodgkin lymphoma (HL)\n  6. ECOG performance status ≤ 2.\n  7. Expected survival of at least 12 weeks.\n  8. Adequate venous access (for apheresis) and no other contraindications for blood cell separation.\n  9. Laboratory tests during screening must meet the following requirements, and the hematological assessment must not have received cell growth factors within 7 days (long-acting colony-stimulating factors (G-CSF\u002FPEG-CSF) require a 2-week interval) or platelet transfusions:\n\n     1. Absolute neutrophil count ≥ 1.0×10\\^9\u002FL.\n     2. Hemoglobin ≥ 60 g\u002FL (without red blood cell transfusion in the last 7 days).\n     3. Platelets ≥ 50×10\\^9\u002FL (unrestricted for CLL indications).\n     4. Total bilirubin ≤ 1.5× the upper limit of normal (ULN); or total bilirubin ≤ 3× ULN when the tumor invades liver tissue.\n     5. Aspartate transaminase (AST), alanine transaminase (ALT) ≤ 2.5×ULN, with AST\u002FALT ≤ 5×ULN when the tumor invades liver tissue.\n     6. Creatinine \\\u003C 1.5× ULN and estimated creatinine clearance ≥ 60 mL\u002Fmin.\n  10. Ejection fraction ≥ 45%, with echocardiogram (ECHO) confirming no pericardial effusion (excluding small or physiological amounts), and electrocardiogram results with no clinical significance.\n  11. Baseline oxygen saturation \\> 92% without supplemental oxygen.\n  12. Women of childbearing potential must have a negative serum or urine pregnancy test result (women who have undergone surgical sterilization or have been postmenopausal for at least 2 years are not considered of childbearing potential).\n\nExclusion Criteria:\n\n* Subjects are not eligible to participate in this study if they meet any of the following criteria:\n\n  1. MRI of the brain shows evidence of central nervous system lymphoma; active primary central nervous system DLBL, unless central nervous system involvement has been effectively treated (i.e., participant is asymptomatic), and there has been more than a 4-week gap since local treatment.\n  2. Active central nervous system diseases, such as epilepsy, cerebrovascular ischemia\u002Fhemorrhage, dementia, cerebellar diseases, or any autoimmune diseases with central nervous system involvement.\n  3. History of or concurrent diagnosis of malignancies other than CD19+ malignancies.\n  4. Clinically significant heart disease or arrhythmias that cannot be controlled with medication.\n  5. Presence or suspicion of fungal, bacterial, viral, or other infections that are uncontrolled or require intravenous antibiotics for treatment; uncomplicated urinary tract infections and uncomplicated bacterial pharyngitis are allowed.\n  6. Positive for hepatitis B (HBsAg positive and HBV DNA \\>1000 copies\u002FmL) and hepatitis C (positive for HCV antibodies); syphilis or human immunodeficiency virus (HIV) infection.\n  7. Presence of any indwelling catheter or drainage tube (such as percutaneous nephrostomy, indwelling Foley catheter, bile drainage tube, or pleural\u002Fperitoneal\u002Fpericardial catheter); use of specialized central venous access devices like Port-A-Cath® or Hickman® catheters is allowed.\n  8. History of using any of the following medications:\n\n     1. Lenalidomide within 1 day before the apheresis.\n     2. Idelalisib (oral PI3Kδ inhibitor) within 2 days before the apheresis.\n     3. Short-acting targeted therapy (like tyrosine kinase inhibitors) within 72 hours before the apheresis.\n     4. Venetoclax (BCL-2 inhibitor) within 4 days before the apheresis.\n     5. Long-acting growth factors (like pegylated filgrastim) within 14 days before the apheresis, or short-acting growth factors or mobilization agents (like G-CSF\u002Ffilgrastim, plerixafor) within 5 days before the apheresis.\n     6. Pharmacological doses of corticosteroids (\\>5mg\u002Fday of prednisone or equivalent doses of other corticosteroids) or other immunosuppressive agents within 7 days before enrollment.\n     7. Radiation therapy within 14 days before enrollment.\n     8. Systemic cytotoxic drugs, including low-dose maintenance chemotherapy (cyclophosphamide, ifosfamide, bendamustine, methotrexate, or mercaptopurine, vincristine, etc.), within 14 days before enrollment. If bridging therapy is given after apheresis, there should be more than a 7-day gap between bridging therapy and CAR-T cell infusion.\n     9. Anti-PD1 or anti-PDL1 within 4 weeks prior to enrollment.\n     10. Live vaccines within 4 weeks prior to enrollment.\n     11. Donor lymphocyte infusion (DLI) within 4 weeks prior to enrollment.\n     12. Immune stimulation or immunosuppressive therapy (like interferon-α, interferon-β, IL-2, etanercept, infliximab, tacrolimus, cyclosporine, or mycophenolate mofetil) within 4 weeks prior to enrollment.\n     13. Use of clofarabine or cladribine within 3 months prior to enrollment, or use of PEG-asparaginase within 3 weeks prior to enrollment.\n  9. Active graft-versus-host disease (GVHD) rated ≥2 on the CIBMTR acute GVHD grading system or requires systemic steroids at doses greater than physiological levels.\n  10. A history of autoimmune diseases in the past 2 years (like Crohn's disease, rheumatoid arthritis, or systemic lupus erythematosus) that has caused damage to end organs or requires systemic immunosuppression\u002Fsystemic disease-modifying agents.\n  11. A history of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant heart diseases within the 12 months prior to enrollment.\n  12. A history of genetic syndromes associated with bone marrow failure, such as Fanconi anemia, Kostmann syndrome, or Schwachman-Diamond syndrome.\n  13. A history of symptomatic deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation in the 6 months before enrollment. Subjects need to be on preventive anticoagulant medication.\n  14. A history of other malignancies (except for non-melanoma skin cancer, in situ breast\u002Fcervical cancer, and other malignant tumors that have been effectively controlled without treatment in the past five years).\n  15. Use of other investigational medicinal products within 30 days prior to screening.\n  16. Pregnant or breastfeeding women of childbearing age. Women who have undergone surgical sterilization or are postmenopausal for at least 2 years are not considered of childbearing potential.\n  17. Male and female subjects unwilling to practice contraception from the time they agree to treatment until 12 months after completing the lymphodepleting chemotherapy or CAR-T infusion (whichever is longer).\n  18. Any medical activities that could interfere with the safety or efficacy evaluation of the study treatment.\n  19. In the judgment of the investigator, subjects are unlikely to complete all required study visits or procedures (including follow-ups) or to comply with the study participation requirements.",{"count":20,"type":21},[24],"This study is an exploratory clinical trial of a single-center, open-label, single-dose treatment of anti-CD20\u002FCD30-CAR-T cells in subjects with relapsed\u002Frefractory lymphoma.",[52],"Relapsed\u002FRefractory Lymphoma","2024-09-04",{"date":55,"type":32},"2024-09-19",{"date":34,"type":32},{"date":36,"type":21},{"name":38,"class":39},""]