BCMA-CAR-T in Relapsed/Refractory Multiple Myeloma

Study Overview
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Brief Summary
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Evaluation of the safety and efficacy of BCMA nanobody CAR-T cells in relapsed/refractory myeloma

Detailed Description
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There are no effective regimens for relapsed/refractory myeloma. BCMA express extensively in mature B cells and plasma cells. Myeloma cells express BCMA universally. BCMA signal pathway can induce plasma cell proliferation and survival, down-regulation of BCMA could control the progression of myeloma. The BCMA CAR used in this study consists of BCMA nanobody, CD8 hinge, transmembrane region and 4-1bb co-stimulation domain.

Official Title
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a Single-center, One Arm, Open Clinical Study of BCMA Nanobody CAR-T Cell in Refractory/Relapsed Myeloma

Conditions
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Relapsed/Refractory Myeloma

Intervention / Treatment
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* Drug: BCMA nanobody CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 and ≤70 years old and the expected lifetime >3 months Active myeloma according to IMWG criteria, and BCMA positive by immunohistochemistry or flow cytometry No effective treatment option available ECOG score 0-2 Sufficient heart, liver, kidney function (heart: no heart disease or coronary heart disease, patient heart function NYHA grade 1-2; liver: TBIL ≤ 3ULN, AST ≤ 2.5ULN, ALT ≤ 2.5ULN; kidney: Cr≤ 1.25ULN); smoothly peripheral superficial veins No other serious diseases that conflict with this protocol (eg, autoimmune diseases, immunodeficiency, organ transplantation) No history of other malignancies Women of childbearing age must be negative for blood pregnancy test within 7 days and must take appropriated contraceptive measures during and 3 months after the study The patient himself agrees to participate in this clinical study and signed the informed consent Exclusion Criteria: Severe infectious 4 weeks before enrollment Active hepatitis B or C viral hepatitis, HIV, Severe autoimmune disease or immunodeficiency disease Severe allergies Severe mental disorder Patients who used high-dose glucocorticoids within 1 week Participation in other clinical studies in the past 3 months or having been treated with other gene products

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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental group<br>BCMA nanobody CAR-T cells | Drug: BCMA nanobody CAR-T cells<br>* step 1: Collect 50-100ml of peripheral blood for culture of BCMA nanobody CAR- T cells. step 2. After 72 hours, pretreated with FC regimen, details as follow Cyclophosphamide 600-800mg/m2 for 2 days Fludarabine 25-30mg/m2 for 3 days. step 3: After another 48 hours transfusion the cells back to the patients the numbers of infused CAR T cells are 5x106 /kg for the first 3 patients, 1.5x107 /kg for the second 3 patients and 4.5x107 /kg for the third 3 patients. After finishing this, another 6 patients will be enrolled for observation of efficacy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| occurrence of study related adverse events | safety of CAR-T cells | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment response rate | response rate according to IMWG criteria | 3 months and 6 months | 
| copy number of CAR-T cells | copy number of CAR-T cells | one year |