[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100473255":3},{"organization":4,"armGroups":7,"interventions":47,"overallOfficials":61,"centralContacts":66,"locations":75,"responsibleParty":94,"collaborators":46,"id":96,"slug":97,"hasResults":98,"nctId":99,"briefTitle":100,"officialTitle":101,"acronym":46,"eligibilityCriteria":102,"healthyVolunteers":98,"sex":103,"minAge":104,"maxAge":105,"enrollmentInfo":106,"targetDuration":46,"studyType":109,"phases":110,"briefSummary":113,"conditions":114,"keywords":126,"overallStatus":78,"whyStopped":46,"lastUpdateSubmitDate":132,"lastUpdatePostDateStruct":133,"startDateStruct":136,"completionDateStruct":138,"leadSponsor":140,"locationsCount":141},{"fullName":5,"class":6},"National Institutes of Health Clinical Center (CC)","NIH",[8,16,20,24,27,31,34,38,42],{"label":9,"type":10,"description":11,"interventionNames":12},"1\u002FPhase I Dose Escalation-with standard LD - CLOSED","EXPERIMENTAL","CD19\u002FCD22-CAR-transduced T cells at escalating dose + standard LD (75 mg\u002Fmg2 Flu+ 900 mg\u002Fm2 Cy)",[13,14,15],"Biological: CD19\u002FCD22-CAR-transduced T cells","Drug: cyclophosphamide","Drug: fludarabine",{"label":17,"type":10,"description":18,"interventionNames":19},"1b\u002FPhase 1 Dose Escalation - low disease burden","CD19\u002FCD22-CAR-transduced T cells",[13,14,15],{"label":21,"type":10,"description":22,"interventionNames":23},"2\u002FPhase I Dose Escalation- with intensified LD - CLOSED","CD19\u002FCD22-CAR-transduced T cells + standard LD (120 mg\u002Fm2 Flu + 1200 mg\u002Fm2 Cy)",[13,14,15],{"label":25,"type":10,"description":18,"interventionNames":26},"2b\u002FPhase 1 Dose Escalation - high disease burden",[13,14,15],{"label":28,"type":10,"description":29,"interventionNames":30},"3\u002FPhase II Dose Expansion- with low disease burden - CLOSED","CD19\u002FCD22-CAR-transduced T cells at MTD\u002For highest dose administered with LD",[13,14,15],{"label":32,"type":10,"description":18,"interventionNames":33},"3b Phase I Dose Escalation: Either CD19 or CD22 positivity",[13,14,15],{"label":35,"type":10,"description":36,"interventionNames":37},"4\u002FPhase II Dose Expansion- with high disease burden - CLOSED","CD19\u002FCD22-CAR-transduced T cells at MTD\u002For highest dose administered with LD regimen #2",[13,14,15],{"label":39,"type":10,"description":40,"interventionNames":41},"4b Phase II Dose Expansion in B-ALL\u002FB-LBL","CD19\u002FCD22-CAR-transduced T cells at RP2D",[13,14,15],{"label":43,"type":44,"description":45,"interventionNames":46},"A\u002FPre-treatment","NO_INTERVENTION","All participants enrolled on the study prior to treatment initiation.",null,[48,52,57],{"type":49,"name":18,"description":50,"armGroupLabels":51,"otherNames":46},"BIOLOGICAL","CD19\u002FCD22-CAR-transduced T cells on D0 after lymphodepleting preparative regimen",[9,17,21,25,28,32,35,39],{"type":53,"name":54,"description":55,"armGroupLabels":56,"otherNames":46},"DRUG","cyclophosphamide","Cyclophosphamide will be diluted in an appropriate solution and infused over one hour. The dose will be based on the patient s body weight, at 900 mg\u002Fm2\u002Fdose after fludarabine infusion.",[9,17,21,25,28,32,35,39],{"type":53,"name":58,"description":59,"armGroupLabels":60,"otherNames":46},"fludarabine","Fludarabine is administered as an IV infusion in an appropriate solution over 30 minutes. To prevent undue toxicity the dose will be based on BSA (25 mg\u002Fm2\u002Fdose).",[9,17,21,25,28,32,35,39],[62],{"name":63,"affiliation":64,"role":65},"Sara K Silbert, M.D.","National Cancer Institute (NCI)","PRINCIPAL_INVESTIGATOR",[67,72],{"name":68,"role":69,"phone":70,"phoneExt":46,"email":71},"NCI Ped LeukemiaLymph Cell Tx Tm","CONTACT","(240) 760-6970","ncilltct@mail.nih.gov",{"name":63,"role":69,"phone":73,"phoneExt":46,"email":74},"(240) 858-3666","sara.silbert@nih.gov",[76],{"facility":77,"status":78,"city":79,"state":80,"zip":81,"country":82,"countryCode":83,"cosmosGeoPoint":84,"geoPoint":89,"contacts":90},"National Institutes of Health Clinical Center","RECRUITING","Bethesda","Maryland","20892","United States","US",{"type":85,"coordinates":86},"Point",[87,88],-77.10026,38.98067,{"lat":88,"lon":87},[91],{"name":92,"role":69,"phone":93,"phoneExt":46,"email":46},"For more information at the NIH Clinical Center contact National Cancer Institute Referral Office","888-624-1937",{"type":95,"investigatorFullName":46,"investigatorTitle":46,"investigatorAffiliation":46,"oldNameTitle":46,"oldOrganization":46},"SPONSOR","100473255","phase-1-cd19cd22-bicistronic-chimeric-antigen-receptor-car-t-cells-in-children-and-young-adults-with-recurrent-or-refractory-b-cell-malignancies-100473255",false,"NCT05442515","CD19\u002FCD22 Bicistronic Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory B Cell Malignancies","Phase 1\u002F2 Dose Escalation Study of CD19\u002FCD22 Bicistronic Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory B Cell Malignancies","* INCLUSION CRITERIA:\n* Diagnosis\n\n  * Participant must:\n\n    * Have pathology confirmed B cell ALL (not isolated to the testis or CNS), CML with ALL transformation, or high-grade lymphoma (e.g., Burkitt's lymphoma, B-lymphoblastic lymphoma, diffuse large B-cell lymphoma, inclusive of low-grade lymphoma that has transformed to high grade disease); and\n    * Have relapsed or been refractory after at least one standard chemotherapy regimen and at least one salvage treatment. Participants with Philadelphia chromosome + ALL must have failed prior tyrosine kinase inhibitor; and\n    * Be ineligible for allogeneic stem cell transplant (SCT), have refused SCT, or have recurred after SCT; and\n    * Be unable to access (in a timely manner), ineligible for, or have relapsed\u002Ffailed after or not responded to a commercially available CD19 CAR T-cell construct; and\n  * Have evidence of at least minimal residual disease or PET-avid disease (lymphoma) at the time of enrollment.\n* CD22\u002FCD19 expression\n\n  * Cohorts A1b, B1b, C2b\n\n    * CD19 must be detected on \\>15% of the malignant cells by immunohistochemistry or \\> 80% by flow cytometry.\n    * CD22 positivity must be confirmed.\n  * Cohorts D1b, 2 B-ALL\n\n    * CD19 or CD22 positivity must be confirmed\n    * Age \\>= 3 years of age and \\\u003C=39 years of age at time of enrollment.\n    * Clinical Performance status: Participants \\>= 16 years of age: Karnofsky \\>= 50%; Participants \\\u003C 16 years of age: Lansky scale \\>= 50%.\n* Participants must have adequate organ and marrow function as defined below:\n\n  * leukocytes \\>= 750\u002FmcL\\*\n  * platelets \\>= 50,000\u002FmcL\\*\n  * total bilirubin \\\u003C=2 X ULN (except in the case of participants with documented Gilbert's disease \\> 3x ULN)\n  * AST(SGOT)\u002FALT(SGPT) \\\u003C=10 X institutional upper limit of normal\n  * creatinine \\\u003C= the maximum for age listed in the table below OR\n  * measured creatinine clearance \\>=60 mL\u002Fmin\u002F1.73 m\\^2 for participants with creatinine levels above the max listed below per age.\n\n    * Age (Years) \\\u003C= 5 \u002F Maximum Serum Creatinine (mg\u002FdL) \\\u003C= 0.8\n    * Age (Years) 6 to \\\u003C= 10 \u002F Maximum Serum Creatinine (mg\u002FdL) \\\u003C= 1.0\n    * Age (Years) \\>10 \u002F Maximum Serum Creatinine (mg\u002FdL) \\\u003C= 1.2\n\n      * a participant will not be excluded because of pancytopenia \\>= Grade 3 if it is due to underlying bone marrow involvement by leukemia\n* Central nervous system (CNS) Status\n* Participants with leukemia with CNS 1 and 2 disease are eligible in the absence of exclusion criteria\n* Participants of child-bearing or child-fathering potential must be willing to practice effective birth control from the time of enrollment until 12 months following completion of study treatment for women and for 4 months following completion of study treatment for men.\n* Participants who are breastfeeding or plan to breastfeed must agree to discontinue\u002Fpostpone breastfeeding while on study therapy and until 1 month after the administration of CAR.\n* Cardiac function: Left ventricular ejection fraction \\>= 45% or fractional shortening \\>=28%\n* Pulmonary Function\n\n  * Baseline oxygen saturation \\>92% on room air at rest\n* Ability of participant or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.\n* Ability and willingness of participant or Legally Authorized Representative (LAR) to co- enroll on 15-C-0028: Follow-up Evaluation for Gene-Therapy Related Delayed Adverse Events after Participation in Pediatric Oncology Branch Clinical Trials.\n\nEXCLUSION CRITERIA:\n\nParticipants meeting any of the following criteria are not eligible for participation in the study:\n\n* Participants with CNS3 disease, progressing neurologic signs\\* of CNS disease, radiologically detected active CNS lymphoma (\\*resolving manifestation or persistent and\u002For irreversible findings from prior CNS involvement (e.g., blindness) is not exclusionary)\n* Hyperleukocytosis (\\>= 50,000 blasts\u002FmicroL)\n* Positive serum or urine beta-HCG pregnancy test performed at screening.\n* Participants will be excluded based on prior therapy if they fail to meet following washout criteria:\n\n  * Therapy: Systemic Chemotherapy, anti-neoplastic agents, antibody- based therapies\n  * Washout\\*: \\>=2 weeks\n  * Exceptions: 6 weeks for clofarabine or nitrosoureas; No washout for prior intrathecal chemotherapy, steroid therapy, hydroxyurea (no dose increases within prior 2 weeks) or ALL maintenance-type chemotherapy (vincristine, 6-mercaptopurine, oral methotrexate, or a tyrosine kinase inhibitor for participants with Ph+ ALL) provided there is recovery from any acute toxic effects\n  * Therapy: Radiation\n  * Washout\\*: \\>=3 weeks\n  * Exceptions: No time restriction with radiation therapy if the volume of bone marrow treated is less than 10% and the participant has measurable\u002Fevaluable disease outside the radiation window\n  * Therapy: Allogeneic Stem Cell Transplant\n  * Washout\\*: \\>= 100 days since SCT; \\>= 30 days since completion of immunosuppression; \\>= 6 weeks since donor lymphocyte infusion (DLI)\n  * Exceptions: Cannot have evidence of active graft-versus-host disease (GVHD) requiring systemic immunosuppression\n  * Therapy: CAR T-Cell Therapy or other Adoptive Cell Therapy\n  * Washout\\*: \\> 30 days post infusion\n\n    * Washout: Time between therapy and apheresis\n* Positive HIV antibodies consistent with active HIV.\n* Positive hepatitis C antibodies or positive Hepatitis B surface antigen (HbsAG) indicative of current\u002Factive HCV\u002FHBV.\n* Active second malignancy other than in situ carcinoma of the cervix, unless the tumor was treated with curative intent at least two years previously and participant is in remission.\n* History of severe, immediate hypersensitivity reaction attributed to compounds of similar chemical or biologic composition to any agents used in study or in the manufacturing of the cells.\n* Uncontrolled, symptomatic, intercurrent illness or social situations that would limit compliance with study requirements or in the opinion of the PI would pose an unacceptable risk to the participant.","ALL","3 Years","39 Years",{"count":107,"type":108},130,"ESTIMATED","INTERVENTIONAL",[111,112],"PHASE1","PHASE2","Background:\n\nAcute lymphoblastic leukemia (ALL) is the most common cancer in children. About 90% of children and young adults who are treated for ALL can now be cured. But if the disease comes back, the survival rate drops to less than 50%. Better treatments are needed for ALL relapses.\n\nObjective:\n\nTo test chimeric antigen receptor (CAR) therapy. CARs are genetically modified cells created from each patient s own blood cells. his trial will use a new type of CAR T-cell that is targeting both CD19 and CD22 at the same time. CD19 and CD22 are proteins found on the surface of most types of ALL.\n\nEligibility:\n\nPeople aged 3 to 39 with ALL or related B-cell lymphoma that has not been cured by standard therapy.\n\nDesign:\n\nParticipants will be screened. This will include:\n\nPhysical exam\n\nBlood and urine tests\n\nTests of their lung and heart function\n\nImaging scans\n\nBone marrow biopsy. A large needle will be inserted into the body to draw some tissues from the interior of a bone.\n\nLumbar puncture. A needle will be inserted into the lower back to draw fluid from the area around the spinal cord.\n\nParticipants will undergo apheresis. Their blood will circulate through a machine that separates blood into different parts. The portion containing T cells will be collected; the remaining cells and fluids will be returned to the body. The T cells will be changed in a laboratory to make them better at fighting cancer cells.\n\nParticipants will receive chemotherapy starting 4 or 5 days before the CAR treatment.\n\nParticipants will be admitted to the hospital. Their own modified T cells will be returned to their body.\n\nParticipants will visit the clinic 2 times a week for 28 days after treatment. Follow-up will continue for 15 years....",[115,116,117,118,119,120,121,122,123,124,125],"B-NHL","B-Non Hodgkin Lymphoma","Acute Lymphocytic Leukemia","Acute Lymphoblastic Leukemia","B-precursor ALL","B-All","Lymphoma, Non-Hodgkin","Leukemia, Lymphocytic, B Cell","B-Cell Lymphoma","B-Cell Leukemia","Acute Lymphoid Leukemia",[127,128,129,130,131,120,119,118,117,116],"Philadelphia chromosome + ALL","Lymphoma","CD-22 Expressing Tumor","CD-19 expressing tumor","Adoptive Immunotherapy","2026-06-30",{"date":134,"type":135},"2026-07-01","ACTUAL",{"date":137,"type":135},"2022-12-28",{"date":139,"type":108},"2029-07-01",{"name":64,"class":6},1]