CRISPR-Edited Allogeneic Anti-BCMA CAR-T Cell Therapy in Patients With Relapsed/Refractory Multiple Myeloma

Study Overview
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Brief Summary
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This is a Phase 1 study to evaluate the safety of CB-011 (the study treatment), an allogeneic chimeric antigen receptor (CAR-T) cell therapy that targets the B cell maturation antigen (BCMA), to determine the best dose of CB-011, and to assess the effectiveness of CB-011 in treating multiple myeloma that has come back (relapsed) or that is no longer responding to other treatment (refractory).

Official Title
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A Phase 1, Multicenter, Open-Label Study of CB-011, a CRISPR-Edited Allogeneic Anti-BCMA CAR-T Cell Therapy in Patients With Relapsed/Refractory Multiple Myeloma (CaMMouflage Trial)

Conditions
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Relapsed/Refractory Multiple Myeloma

Intervention / Treatment
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* Biological: CB-011


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of relapsed/refractory multiple myeloma (MM) with measurable disease (according to IMWG diagnostic criteria.) Received at least 3 prior MM treatment lines of therapy which must include a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody as part of a prior line of therapy, either in monotherapy or in combination. Eastern Cooperative Oncology Group performance status grade of 0 or 1. Adequate hematologic, renal, hepatic, pulmonary, and cardiac function. Exclusion Criteria: Prior treatment with CAR-T cell therapy directed at any target. Autologous stem cell transplant within the last 6 weeks before lymphodepletion. Allogeneic stem cell transplant within 6 months before lymphodepletion. Known active or prior history of CNS involvement. Stroke or seizure within 6 months of signing ICF. Seropositive for or history of human immunodeficiency virus. Vaccinated with live, attenuated vaccine within 4 weeks prior to lymphodepletion. Hepatitis B infection. Hepatitis C infection. Known life-threatening allergies, hypersensitivity, or intolerance to CB-011 or its excipients.

Ages Eligible for Study
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Minimum Age: 18 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: CB-011<br>Part A Escalation with CB-011 in ascending doses using a traditional 3+3 design. Part B Expansion. Up to 30 participants will be enrolled to receive CB-011 at the RDE/MTD and/or RP2D determined in Plan A | Biological: CB-011<br>* CB-011 allogeneic CAR T cell therapy targeting BCMA Cyclophosphamide Chemotherapy for lymphodepletion Fludarabine Chemotherapy for lymphodepletion<br>* Other names: Fludarabine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (Part A) Number of patients with dose limiting toxicities (DLT) | Number of patients with DLTs during the 28 days following the first administration of CB-011. | 28 days | 
| (Part B) Overall Response Rate (ORR) | The ORR will be evaluated by International Myeloma Working Group (IMWG) criteria. | 12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR-T Cells, BCMA, CaMMouflage, Allogeneic, Multiple Myeloma, Relapse Refractory Multiple Myeloma, Cell Therapy, Cellular Immuno-therapy, CB11A, CB-011, CB-011A, CAR-T, Anti BCMA, ALLO CAR T