A Feasibility and Safety Study of Dual Specificity CD38 and BCMA CAR-T Cell Immunotherapy for Relapsed or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory Multiple Myeloma,however, a subset of patients relapse due to the loss of target in tumor cells.Dual Specificity CD38 and BCMA CAR-T cells can recognize and kill the malignant cells through recognition of CD38 or BCMA. This is a phase 1/2 study designed to determine the safety of dual specificity CD38 and BCMA CAR-T cells and the feasibility of making enough to treat patients with relapsed or refractory Multiple Myeloma.

Detailed Description
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PRIMARY OBJECTIVES: To evaluate the feasibility and safety of dual specificity CD38 and BCMA CAR-T cells in patients with relapsed or refractory Multiple Myeloma. To evaluate the duration of in vivo persistence of adoptively transferred T cells, and the phenotype of persisting T cells.Real Time polymerase chain receptor (RT-PCR) and Flow cytometry(FCM) analysis of PB,BM and lymph node will be used to detect and quantify survival of universal dual specificity CD38 and BCMA CAR-T cells over time. SECONDARY OBJECTIVES: 1.For patients with detectable disease, measure anti-tumor response due to dual specificity CD38 and BCMA CAR-T cell infusions. 2.The CAR-T cells will be administered by i.v. injection over 20-30 minutes as a using Day 0: 1-5x10e6/kg total dose on day 0.

Official Title
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Phase I/II Study to Evaluate Treatment of Relapsed or Refractory Multiple Myeloma With Dual CAR-T Cells Targeting CD38 and BCMA

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: Dual Specificity CD38 and bcma CAR-T Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participant 12 Years to 70 Years (Child, Adult, Senior) Patient with relapsed or refractory Multiple Myeloma,multiple myeloma cell express CD38(over 50%) and BCMA (over 50%) Estimated life expectancy ≥ 12 weeks (according to investigator's judgement) Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 Adequate organ function Exclusion Criteria: Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis Richter's syndrome Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis is allowed), Prophylactic antibiotic, antiviral and antifungal treatment is permissible Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening Patient has an investigational medicinal product within the last 30 days prior to screening Previous treatment with investigational gene or cell therapy medicine products Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary Pregnant or nursing women

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 70 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: Dual Specificity CD38 and bcma CAR-T Cells|1) Biological: Dual Specificity CD38 and BCMA CAR-T Cells,2)1-5X10E6/Kg|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability |  | 24weeks | 
| MTD of dual specificity CD38 and BCMA CAR-T cells | The highest dose of dual specificity CD38 and BCMA CAR-T cells that is estimated to result in defined Dose Limiting Toxicity (DLT) with the exception of allowable 'expected' AEs associated with the intravenous infusion of dual specificity CD38 and BCMA CAR-T cells | 4 weeks | 
| Copies numbers of CAR in peripheral blood(PB), bone marrow(BM)and lymph nodes |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six-month Objective response rate of complete remission and partial remission |  | 24 weeks | 
| Six-month Overall survival |  | 24 weeks | 
| Six-month Progression free survival |  | 24 weeks |