Autologous CD8+ T-cells Expressing an Anti-BCMA CAR in Patients With Myeloma

Study Overview
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Brief Summary
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This Phase I/II study will test the safety and anti-myeloma activity of ascending doses of Descartes-08 (autologous CD8+ T-cells expressing an anti-BCMA chimeric antigen receptor) in eligible patients with active multiple myeloma.

Official Title
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Combined Phase I-Phase II Study of Autologous CD8+ T-cells Transiently Expressing a Chimeric Antigen Receptor Directed to B-Cell Maturation Antigen in Patients With Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: Descartes-08
* Drug: Fludarabine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (condensed): Multiple myeloma that is double-refractory to a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) after at least 2 prior lines of therapy OR have failed at least 3 prior lines of therapy Measurable disease activity as indicated by serum or urine M-protein, serum free light chain, biopsy-proven plasmacytoma, >5% bone marrow plasma cells. Adequate vital organ function as indicated by ANC (>1000/uL), platelet count (>50,000/uL), hemoglobin (>8 g/dL), serum ALT and AST (each <3.0 x upper limit of normal), total bilirubin (<2 mg/dL), creatinine clearance (>30 mL/min), and cardiac ejection fraction (>45%) Exclusion Criteria (condensed): NOTE: Prior anti-BCMA or CAR-T therapy is NOT exclusionary Active plasma cell leukemia Pregnant or lactating Active, uncontrolled infection Active and severe auto-immune disease Active arrhythmia, or obstructive or restrictive pulmonary disease Central nervous system disease

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Descartes-08 plus fludarabine/cyclophosphamide pretreat<br>Autologous CD8+ T-cells transiently expressing an anti-BCMA chimeric antigen receptor | Biological: Descartes-08<br>* autologous CD8+ T-cells transiently expressing an anti-BCMA chimeric antigen receptor<br>* Other names: CAR-T cells;Drug: Fludarabine<br>* intravenous fludarabine<br>Drug: Cyclophosphamide<br>* intravenous cyclophosphamide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence (number) of Treatment-Emergent Adverse Events [Safety and Tolerability] | Incidence (number) of Treatment-Emergent Adverse Events [Safety and Tolerability]. Descriptive statistics by incidence rate, body system classification, severity, and causality [per protocol definitions] | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment response | IMWG treatment response criteria | 1, 3, 6, 9 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Descartes-08, CAR T Cell, CART, CAR-T, CAR T-Cell, Multiple Myeloma, BCMA, B-cell maturation antigen, B cell maturation antigen