Humanized CAR-T Cells of Anti-BCAM and Anti-CD19 Against Relapsed and Refractory Multiple Myeloma

Study Overview
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Brief Summary
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This is a single arm, open-label, single center study to evaluate the safety and efficacy of BCMA/CD19 CAR-T cells in patients with BCMA+，CD19+ relapsed or refractory multiple myeloma.

Detailed Description
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CD19 has been extensively evaluated as a therapeutic target for relapsed or refractory multiple myeloma by chimeric antigen receptor T cell therapy,this is a single arm, open-label, single center study to preliminary explore the safety, tolerability and cellular pharmacokinetics of Anti-BCMA and Anti-CD19 CAR-T cells in the treatment of relapsed or refractory multiple myeloma.

Official Title
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Study Evaluating the Safety and Efficacy With Sequential Infusion of Humanized CAR-T Cells of Anti-BCAM and Anti-CD19 Against Relapsed and Refractory Multiple Myeloma

Conditions
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Relapsed or Refractory Multiple Myeloma

Intervention / Treatment
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* Biological: Autologous BCMA CAR-T cells and CD19 CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18-70 years old Estimated Survival time > 12 weeks Relapsed and refractory multiple myeloma were confirmed by physical examination, pathological examination, laboratory examination and imaging Chemotherapy failure or recurrent multiple myeloma Glutamic-pyruvic transaminase, glutamic oxalacetic transaminase< 3 fold of normal level Bilirubin<2.0mg/dl Karnofsky Performance Status>50% at the time of screening Adequate pulmonary, renal, hepatic, and cardiac function Fail in autologous haemopoietic stem cell transplantation Not suitable for stem cell transplantation conditions or abandoned due to conditions Free of leukocytes removal contraindications Voluntarily join CAR-T clinical trial ,Understand and sign written informed consent Exclusion Criteria: The patient is a pregnant or breastfeeding woman, or is a woman with a pregnancy plan within six months Patients have infectious diseases (such as HIV, active tuberculosis, etc.) The patient is an active hepatitis B or hepatitis C infection Feasibility assessment proves that the efficiency of transduction of lymphocyte is below 10% or the lymphocyte cannot be propagated Abnormal vital signs Subjects with mental or psychological illness who cannot be combined with treatment and efficacy evaluation. Highly allergic constitution or history of severe allergies, especially allergy to interleukin-2 General infection or local severe infection, or other infection that is not controlled Dysfunction in lung, heart, kidney and brain Severe autoimmune diseases Other symptoms that are not applicable for CAR-T

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mixed BCMA/CD19 CAR-T Transfer<br>Subjects with BCMA/CD19+ multiple myeloma will be infused with CD19-targeting CAR T Cells and BCMA-targeting CAR T Cells in one time or in parts | Biological: Autologous BCMA CAR-T cells and CD19 CAR-T cells<br>* Autologous BCMA CAR-T cells and CD19 CAR-T cells with average 1-5*10^6 cells/kg body weight,separately.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Assessment of ORR (ORR = sCR+CR+VGPR+PR ) at 1 months of treatment | 2 year | 
| minimal residual disease（MRD） | Assessment of MRD negative overall response rate at 3 months of treatment | 2 year | 
| Progression-free survival (PFS) | Assessment of Progression-free survival (PFS) at 6 months of treatment | 2 year | 
| Overall survival (OS) | Assessment of overall survival (OS) at 6 months of treatment | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (incidence of adverse events defined as dose-limited toxicity) | Occurrence of study related adverse events defined as NCI CTCAE 4.0 > grade 3 possibly, probably, or definitely related to study treatment. | Study treatment until Week 24 | 
| Expression of CD19 CART cells | Expression of CD19 CART cells in blood, bone marrow by Quantitative Polymerase Chain Reaction (q-PCR) and by flow cytometry. | 2 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed and refractory multiple myeloma; CAR-T