A Clinical Study to Evaluate the Safety and Efficacy of INS19 CAR-T Cells for the Treatment of Relapsed or Refractory Acute B Lymphoblastic Leukemia
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Leukemia, B-cell
- Sponsor
- Beijing Immunochina Medical Science & Technology Co., Ltd.
- Enrollment
- 12
- Primary Endpoint
- Incidence of Treatment Related adverse events (AEs)
- Status
- Not Yet Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This study, a single-center, open, single-dose clinical study, was designed to evaluate the safety, tolerability, and pharmacokinetic profile of INS19 CAR-T cells for the treatment of patients with relapsed or refractory acute B lymphoblastic leukemia
Detailed Description
The study is planned to enroll 9-12 patients with relapsed or refractory acute B-lymphoblastic leukemia in a modified "3+3" design with two dose groups of 1×10\^7 cells and 2×10\^7 cells (dose halved for subjects weighing \<40 kg). Each dose group is planned to enroll 3-6 subjects to assess safety, and ultimately the SRC will decide whether to continue to add escalating dose groups or to conduct an extension study in a specific dose group based on available safety and efficacy information, with 3-6 subjects to be enrolled in the extension phase. This study will be divided into a screening period, a cell collection period, a chemotherapy pretreatment period, a return infusion and a follow-up period, and within 28 days of return infusion the investigator will assess whether a DLT (Dose limited toxicity) event has occurred to confirm the safety of this dose group.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with relapsed or refractory acute B-lymphoblastic leukemia who meet one of the following criteria and are diagnosed as CD19 positive by flow cytometry or histology, with the following provisions for the patient's prior treatment:
- •2 or more bone marrow relapses;
- •Chemoresistance: relapse after chemotherapy and failure to achieve complete remission (MRD \>1%) with at least 1 additional course of chemotherapy;
- •Relapse after autologous or allogeneic hematopoietic stem cell transplantation: time from transplantation to reinfusion is at least greater than 6 months;
- •Primary refractory: complete remission not achieved after two courses of standard chemotherapy (MRD \>1%);
- •Philadelphia chromosome-positive (Ph+) patients are required to meet the following criteria: they should have received at least one relapse or refractory treatment with a tyrosine kinase inhibitor (TKI) agent ± chemotherapy or be intolerant of relapse or refractory to treatment with a TKI analog ± chemotherapy; Ph+ acute lymphoblastic leukemia (ALL) known to be accompanied by a T315I mutation, in the absence of an effective treatment with a TKI analog, is not require patients to be treated with TKI analogs ± chemotherapy;
- •Patients must have evaluable evidence of disease (bone marrow morphology suggestive of ≥5% primitive naive cells or bone marrow MRD \>1%);
- •Age 3-70, including boundary values;
- •Expected survival of 3 months or more;
- •Eastern Cooperative Oncology Group (ECOG) score of 0-1 for patients aged 16 years and older (refer to Attachment 1); Lansky score of \>50 for patients under 16 years of age (refer to Attachment 2);
Exclusion Criteria
- •Isolated extramedullary disease relapse;
- •Leukemia patients with symptoms of significant central nervous system invasion and requiring targeted therapy;
- •Prior treatment with a gene product;
- •Plasmapheresis with symptoms of compression (e.g., pleural effusion, abdominal effusion);
- •Patients with cardiac involvement and gastrointestinal involvement;
- •Autoimmune disease requiring systemic immunosuppressive therapy (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus) within 2 years prior to the start of screening;
- •History of myocardial infarction, cardiac angioplasty or stenting, unstable angina pectoris, active arrhythmia, or other clinically significant cardiac disease within 6 months prior to the start of screening; patients with NYHA scores greater than Class I (or is it Class II);
- •Patients with a history of symptomatic deep vein thrombosis or pulmonary embolism within 6 months prior to the start of screening; or requiring long-term antiplatelet therapy; or undergoing anticoagulation therapy;
- •Allergy to the study drug and related ingredients (e.g., albumin);
- •Those with Graft-versus-host disease (GVHD) requiring immunosuppression; or GVHD ≥ grade 2 or on anti-GVHD therapy; use of any medication for the treatment of GVHD within 4 weeks prior to enrollment; or autoimmune disease;
Outcomes
Primary Outcomes
Incidence of Treatment Related adverse events (AEs)
Time Frame: Up to 28 days after CAR-T cell infusion
Incidence of adverse events associated with CAR-T treatment, abnormal clinically significant laboratory findings, including dose-limiting toxicity (DLT) and maximum-tolerated Dose (MTD).
Persistence of CAR-T cells
Time Frame: Up to 24 weeks after CAR-T cell infusion
cell counts and cell percentage in peripheral blood and bone marrow
Secondary Outcomes
- Overall survival (OS)(Up to 24 months after CAR-T cell infusion)
- Minimal residual disease (MRD) negative rate(Up to 24 months after CAR-T cell infusion)
- Duration of response (DOR)(Up to 24 months after CAR-T cell infusion)
- Minimal residual disease (MRD) negative duration(Up to 24 months after CAR-T cell infusion)
- Objective response rate (ORR)(At 28 days, 3 months and 6 months after CAR-T cell infusion)
- Relapse free survival (RFS)(Up to 24 months after CAR-T cell infusion)
- Anti-therapeutic INS19 CAR-T cells antibody(Up to 24 months after CAR-T cell infusion)