CXCR4 Modified Anti-BCMA CAR T Cells for Multiple Myeloma

Study Overview
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Brief Summary
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Multiple myeloma (MM) is an incurable plasma cell cancer that almost all patients eventually relapse despite advancement in treatment strategies. B-cell maturation antigen (BCMA) is a cell surface receptor that expressed primarily by malignant and normal plasma cells. This study aims to evaluate the safety and tolerance CXCR4 modified BCMA CAR T cells in treating standard treatment failed refractory/relapsed multiple myeloma, and will follow dose-escalating cohorts. The efficacy of CXCR4 modified BCMA CAR T will also be investigated.

Official Title
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Phase I Study of A CXCR4 Modified BCMA CAR-T in Patients With Refractory and/or Relapsed Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: CXCR4 modified anti-BCMA CAR T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 to 75 years old. The expected survival ≥ 12 week ECOG ≤ 2 Patients with multiple myeloma that never achieved MR (minor response) or received ≥ 1 line of standard therapy but tumor relapse The liver and renal function is good/adequate organ function; no uncontrolled or active infectious disease Venous channel is unobstructed, which can meet the needs of intravenous drip; no contraindications of mononuclear cell collection Patients can take effective contraceptive measures during the trial period and 1 year after the infusion Voluntary informed consent is given, agree to follow the trial treatment and visit plan Exclusion Criteria: Patients with other uncontrollable cancer Active hepatitis B, hepatitis C, or HIV infection Other uncontrolled active disease Patients with coronary heart disease, angina pectoris, myocardial infarction, cerebral thrombosis, cerebral hemorrhage or any other severe diseases Patients with uncontrollable hypertension(≥ grade II) Patients with history of uncontrollable mental illness Long-term use of immunosuppressants after organ transplantation (inhaled corticosteroids are excluded) Unstable pulmonary embolism or any arteriovenous embolism 30 days before enrollment; Pregnant or lactating women; Men or women who have a pregnancy plan within a year; The patients cannot guarantee effective contraceptive measures during the trial period; Patients with uncontrollable infectious disease or need systematic treatment within the 14 days of enrollment; Patients had other conditions that were not appropriate for the study determined by the researchers.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: CXCR4 modified anti-BCMA CAR T cell therapy<br>CAR T cell therapy | Biological: CXCR4 modified anti-BCMA CAR T cells<br>* intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicities (DLT) | Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration | 2 years | 
| Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR (overall response rate) | Proportion of subjects with the best overall response (BOR) | 3 months，6 months | 
| CRR (complete response rate) | Proportion of subjects with the BOR of sCR+CR at Month 3 | 3 months |