BCMA-CD19 cCAR in Multiple Myeloma and Plasmacytoid Lymphoma

Study Overview
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Brief Summary
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This is a phase I, interventional, single arm, open label, treatment study to evaluate the safety and tolerability of BCMA-CD19 cCAR in patients with relapsed and/or refractory multiple myeloma and plasmacytoid lymphoma.

Detailed Description
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BCMA-CD19 cCAR is a compound Chimeric Antigen Receptor (cCAR) immunotherapy with two distinct functional CAR molecules expressing on a T-cell, directed against the surface proteins BCMA and CD19. BCMA-CD19 cCAR is also aimed to treat multiple myeloma, a challenging disease due to the heterogeneity of myeloma cells, which renders single-antigen targeting CAR T-cell therapy ineffective. BCMA-CD19 cCAR is proposed to target both bulky myeloma cells expressing BCMA, and myeloma stem cells expressing CD19 to effectively eradicate the disease. BCMA-CD19 cCAR is also aimed to treat heterogeneous plasmacytoid lymphoma bearing two types of lymphoma cells, regular lymphoma cells expressing CD19 and plasmacytoid lymphoma cells expressing BCMA. The use of two different targets intends to increase coverage and eradicate cancerous cells before resistance develops in surviving cancer cells that have undergone selective pressures or antigen escape.

Official Title
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BCMA-CD19 cCAR in Relapsed and /or Refractory Multiple Myeloma and Plasmacytoid Lymphoma

Conditions
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Multiple Myeloma in Relapse, Refractory Multiple Myeloma, Plasmacytoid; Lymphoma

Intervention / Treatment
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* Biological: BCMA-CD19 cCAR T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent; Patients volunteer to participate in the research Diagnosis is mainly based on the World Health Organization (WHO) 2008 Patients have exhausted standard therapeutic options Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 1 weeks Female must be not pregnant during the study Exclusion Criteria: Patients declining to consent for treatment Prior solid organ transplantation Potentially curative therapy including chemotherapy or hematopoietic cell transplant Prior treatment with BCMAxCD3 or CD19xCD3 bispecific agents
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
Interventional Model Description: Dose escalation phase: BCMA-CD19 cCAR T cells transduced with a lentiviral vector to express two distinct units of BCMA and CD19 CARs on a T cell with an escalation approach, 2e6 to 10e6 CAR-T cells/kg
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCMA-CD19 cCAR<br>Dose escalation phase: BCMA-CD19 cCAR T cells transduced with a lentiviral vector to express two distinct units of BCMA and CD19 CARs on a T cell with an escalation approach, 2e6 to 10e6 CAR-T cells/kg | Biological: BCMA-CD19 cCAR T cells<br>* BCMA-CD19 cCAR T cells administered to patients, will be either fresh or thawed CAR T cells by IV injection after receiving lymphodepleting chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events after BCMA-CD19 cCAR T cells infusion | Determine the toxicity profile of BCMA-CD19 cCAR T cell therapy | 2 years particularly the first 28 days after infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events | Incidence of treatment-emergent adverse events | up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BCMA, CD19, BCMA-CD19 cCAR T cells, multiple myeloma, plasmacytoid lymphoma