Efficacy and Safety Evaluation of PD1-BCMA-CART

Study Overview
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Brief Summary
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This trial aims to evaluate the safety and efficacy of PD1-BCMA-CART in treating patients with relapsed or refractory multiple myeloma.

Detailed Description
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Using gene editing, chimeric antigen receptors recognizing BCMA were integrated into subject self-derived T cells to obtain a large number of BCMA-CART by in vitro amplification, and BCMA-CART back into the subjects could identify and kill myeloma cells in the subjects.This open-label, dose-escalation study was designed to evaluate the safety and antitumor efficacy of PD1-BCMA-CART in the treatment of relapsed or refractory multiple myeloma.

Official Title
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Clinical Study of the Safety and Efficacy of Non-viral Site-directed Integrated PD1-BCMA-CART in Adult Treatment of Relapsed or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: PD1-BCMA-CART


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have the capacity to give informed consent; Confirmed diagnosis of active MM as defined by NCCN and IMWG criteria; Have a diagnosis of BCMA+ multiple myeloma (MM), (≥ 5% BCMA+ in CD138+ plasma cells by flow cytometry obtained within 45 days of study enrollment); Refractory and relapsed MM patients after > 2 cycles of induction therapy,or,have relapsed or treatment refractory disease following autologous stem cell transplant (ASCT); ECOG score=0-2. Subjects according with any of the following options: Age≥50; Failure with separation of T cells during autologous CART processing; or, Failure with expansion of autologous CART; or, The proportion of T cells in PBMC <10%; or, Won't benefit from autologous CART therapy because of disease progress. Exclusion Criteria: Pregnant or nursing women; Women of reproductive potential must have a negative serum pregnancy test performed within 48 hours of starting conditioning chemotherapy Active infection, HIV infection, syphilis serology reaction positive; Active hepatitis B, hepatitis C at the time of screening Significant hepatic dysfunction as following, SGOT(serum glutamic-oxaloacetic transaminase)> 5 x upper limit of normal; bilirubin > 3.0 mg/dL; Lymphotoxic chemotherapeutic agents within 2 weeks of leukapheresis serious mental disorder; With severe cardiac, liver, renal insufficiency, diabetes and other diseases; Participate in other clinical research in the past three months; previously treatment with any gene therapy products Contraindication to cyclophosphamide or fludarabine chemotherapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: 0.5-2×10^6/kgBW
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PD1-BCMA-CART<br>Each subject will accept one of the following dosages of PD1-BCMA-CART cells intravenously (IV) on day 0: 0.5-2*10^6/KgBW. | Biological: PD1-BCMA-CART<br>* Single infusion of PD1-BCMA-CART administered intravenously (i.v.)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Proportion of patients in whom a response among complete response or partial response, as defined by International Myeloma Working group(IMWG) response criteria , will be observed. | Up to 90 days after T cell infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Severity of Adverse Events as a Measure of Safety and Tolerability | Adverse events assessed according to NCI-CTCAE v5.0 criteria | Up to 35 days after T cell infusion | 
| Duration of persistence of PD1-BCMA-CART | Detect the duration of PD1-BCMA-CART after injection using FACS or Q-PCR | Baseline up to 2 year |