A phase 1/2, open-label, single arm, multicohort, multicenter trial to evaluate the safety and efficacy of JCAR017 in pediatric subjects with relapsed/refractory B-ALL and B-NHL (TRANSCEND PEDALL)

Celgene Corporation0 个研究点目标入组 121 人开始时间: 2018年5月17日最近更新: 2023年12月19日

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Celgene Corporation
入组人数: 121

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•1. Phase 1: Subject < 18 years of age and weighs = 6 kg at the time of signing the informed consent form (ICF)/informed assent form (IAF).
•Phase 2: Subject = 25 years of age and weighs = 6 kg at the time of signing the ICF/IAF.
•2. Subject (when applicable, parental/legal representative) must understand and voluntarily provide permission to the ICF/IAF prior to conducting any study-related assessments/procedures.
•3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
•4. Investigator considers the subject is appropriate for adoptive T cell therapy.
•5. Evidence of CD19 expression via flow cytometry (peripheral blood or bone marrow) or immunohistochemistry (bone marrow biopsy)
•6. Subject has a Karnofsky score of = 50 (subjects = 16 years of age) or a Lansky score = 50 (subjects < 16 years of age).
•7. Diagnosis of B-cell ALL or B-cell NHL as defined below:
•- Phase 1: Subjects with r/r B-ALL, defined as morphological evidence of disease in BM (5% or greater lymphoblast by morphology) and either of the following:
•- First or greater marrow relapse, or
•- Any marrow relapse after allogeneic HSCT, or
•- Primary refractory defined as not achieving a CR or a CRi after 2 or more separate induction regimens (or chemo-refractory as not achieving CR/CRi after 1 cycle of standard chemotherapy for relapsed leukemia), or
•- Ineligible for allogeneic HSCT
•Phase 2: Subjects with one of the following:
•- Cohort 1: r/r B-ALL, defined as morphological evidence of disease in BM (5% or greater lymphoblast by morphology) and either:
•- First or greater marrow relapse, or
•- Any marrow relapse after allogeneic HSCT, or
•- Primary refractory defined as not achieving a CR or a CRi after 2 or more separate induction regimens (or chemo-refractory as not achieving CR/CRi after 1 cycle of standard chemotherapy for relapsed leukemia), or
•- Ineligible for allogeneic HSCT.
•- Cohort 2: MRD+ B-ALL, defined as:
•- < 5% lymphoblasts by morphology with
•- MRD detected by a validated assay at a frequency of 1 x10-4 or greater in BM cells. Subjects eligible for enrollment in Cohort 2 are those with MRD positive morphologic CR2 after re-induction when these subjects had previously experienced an early relapse (< 36 months) after first-line chemotherapy. Subjects who are in MRD+ morphologic CR3 and later, regardless of time to relapse in earlier lines, are also eligible.
•Subjects who are in morphologic relapse at screening (r/r B-ALL) and become MRD+ after bridging chemotherapy are also eligible for treatment in Cohort 2.
•- Cohort 3: r/r B-NHL (DLBCL, BL or PMBCL), defined as
•- Measurable disease after 1 or more lines of chemotherapy and/or having failed HSCT or being ineligible for HSCT.
•Note: Note: B-NHL subjects with secondary CNS lymphoma involvement are eligible however subject selection must consider clinical risk factors for severe neurological AEs and alternative treatment options. Subjects should only be enrolled if the Investigator considers the potential benefit outweighs the risk for the subject.
•8. Subjects with Philadelphia chromosome positive ALL are eligible if they are intolerant to or have failed one or more lines of tyrosine-kinase inhibitor (TKI) therapy or if TKI therapy is contraindicated.
•9. Adequate organ function, defined as:
•- Adequate BM function to receive LD chemotherapy as assessed by the Investigator.
•- Subject with adequate renal function, which is defined as:

排除标准

•1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
•2. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
•3. Subject has any condition that confounds the ability to interpret data from the study.
•4. Subject with a history of another primary malignancy that has not been in remission for at least 2 years prior to enrollment.
•5. Subjects who have received previous CD19-targeted therapy must have CD19-positive disease confirmed since completing the prior CD19-targeted therapy.
•6. Prior CAR T cell or other genetically-modified T cell therapy.
•7. Subject with a previous history of or active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
•8. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment at the time of leukapheresis or JCAR017 infusion.
•9. Subject has presence of acute or chronic graft-versus-host disease (GVHD).
•10. Subject with active autoimmune disease requiring immunosuppressive therapy.
•11. Subject has cardiac disorders (CTCAE version 4.03 Grade 3 or 4) within the past 6 months.
•12. Subject with a concomitant genetic syndrome, with the exception of Down’s syndrome.
•13. Subject with active CNS disease and significant neurological deterioration. Subjects with CNS-2 or CNS-3 involvement are eligible provided they are asymptomatic and do not have significant neurological deterioration and, in the opinion of the study investigator.
•14. Subject with a history or presence of clinically relevant CNS pathology.
•15. Subject is pregnant or nursing.
•16. Subject has used the following:
•Therapeutic doses of corticosteroids (defined as > 0.4 mg [maximum 20 mg/day prednisone] or equivalent) within 7 days prior to leukapheresis or 72 hours prior to JCAR017 infusion. Physiologic replacement, topical, and inhaled steroids are permitted.
•Low-dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide = 300 mg/m2) given after leukapheresis to maintain disease control must be stopped = 7 days prior to LD chemotherapy.
•Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below) within 1 week prior to leukapheresis. Oral anticancer agents, are allowed if at least 3 half-lives have elapsed prior to leukapheresis.
•Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide, ifosfamide, bendamustine) within 2 weeks prior to leukapheresis.
•Experimental agents within 4 weeks prior to leukapheresis unless no response or PD is documented on the experimental therapy and at least 3 half-lives have elapsed prior to leukapheresis.
•Immunosuppressive therapies within 4 weeks prior to leukapheresis and JCAR017 infusion (eg, calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as antitumor necrosis factor [TNF], anti-IL-6, or anti-IL-6R).
•Donor lymphocyte infusions (DLI) within 6 weeks prior to JCAR017 infusion.
•Radiation within 6 weeks prior to leukapheresis. Subjects must have PD in irradiated lesions or have additional non-irradiated lesions to be eligible. Radiation to a single lesion, if additional non-irradiated, measurable lesions are present, is allowed up to 2
•weeks prior t

研究者

发起方

Celgene Corporation

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