Master Protocol for the Phase 1 Study of Cell Therapies in Multiple Myeloma

Study Overview
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Brief Summary
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Master protocol for cell therapy, Phase 1 proof-of-concept studies in relapsed and refractory multiple myeloma and includes long-term safety follow-up.

Detailed Description
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ARM 1 is a non-randomized, open label, multi-site Phase 1 study. CART-ddBCMA is a BCMA directed CAR with a non-scFv binding domain that has been deimmunized. ARM 2 is a non-randomized, open label, multi-site Phase 1 study. Using the bivalent BCMA-Specific Adapter (SPRX001) and Universal CAR-Modified T cell (ARC-T Cells)

Official Title
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Master Protocol for the Phase 1 Study of Cell Therapies for the Treatment of Patients With Relapsed Refractory Multiple Myeloma, Including Long-term Safety Follow-up

Conditions
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Relapsed and Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: CART-ddBCMA
* Drug: ARC-T Plus Anti-BCMA SparX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsed and refractory Multiple Myeloma treated with at least 3 prior regimens of system therapy including Proteosome Inhibitor (PI), immunomodulatory drugs (IMiD), and anti-CD38 antibody (CD38mab); or has triple-refractory disease Documented measurable disease Adequate organ function Life expectancy > 12 weeks, Eastern Cooperative Group Performance Status 0-1 Exclusion Criteria: Plasma Cell Leukemia or History of Plasma Cell Leukemia Patients with a history of severe hypersensitivity to DMSO should be excluded Contraindication to fludarabine or cyclophosphamide Severe uncontrolled intercurrent illness (e.g., infection) or laboratory abnormalities Active central nervous system disease involvement by malignancy or active CNS pathology

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ARM 1<br>Phase I study of BCMA-specific CAR-modified T-cell therapy using alternative binding domain, for the treatment of patients with relapsed and refractory multiple myeloma | Drug: CART-ddBCMA<br>* Chimeric Antigen Receptor T cells<br>|
| Experimental: Arm 2<br>Phase 1 Study of Bivalent BCMA-Specific Adapter (SPRX001) and Universal CAR-Modified T cell (ARC-T Cells) for the Treatment of Patients with Relapsed and Refractory Multiple Myeloma | Drug: ARC-T Plus Anti-BCMA SparX<br>* Chimeric Antigen Receptor T cells plus SparX protein<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs), including DLT(s) |  | 24 months | 
| Establish the RP2D of the investigational agent |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best overall response (BOR) by IMWG Consensus Criteria |  | 24 months | 
| ORR by IMWG Consensus Criteria |  | 24 months | 
| In vivo pharmacokinetics | expansion and persistence of investigational agent in peripheral blood/target tissues | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BCMA, Myeloma, Chimeric