BCMA Chimeric Antigen Receptor Expressing T Cells Therapy for Relapsed/Refractory Multiple Myeloma

Study Overview
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Brief Summary
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The goal of this clinical trial is to study the feasibility and efficacy of anti-B-Cell Maturation Antigen (BCMA) expressing T cells in treating patients with multiple myeloma.

Detailed Description
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Participants with BCMA-positive relapsed/refractory multiple myeloma can participate if all eligibility criteria are met. Tests required to determine eligibility include disease assessments, a physical exam, Electrocardiograph, CT/MRI/PET, and blood draws. Participants receive chemotherapy prior to the infusion of BCMA CAR+ T cells. After the infusion, participants will be followed for side effects and effect of BCMA CAR+ T cells. Study procedures may be performed while hospitalized.

Official Title
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A Phase I Clinical Trial of T-Cells Targeting B-Cell Maturation Antigen for Subjects With Relapsed/Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: Anti-BCMA CAR-T cells
* Drug: Fludarabine
* Drug: Cyclophosphamide
* Drug: Immune inhibitors


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Expected survival > 12 weeks Diagnosis of Multiple Myeloma by MWG criteria 20 Patients previously received at least 3 different prior treatment regimens for multiple myeloma, including alkylating agent, protein inhibitors, and immunomodulator, and have disease progression in the past 60 days Important organs function enough to tolerate this therapy At least 90 days after stem cell transplantation Accessible to intravenous injection, and no white blood cell collection contraindications Sexually active patients must be willing to utilize one of the more effective birth control methods for 30 days after the CTL infusion. Male partner should use a condom Able to understand and sign the Informed Consent Document. Exclusion Criteria: Patients with symptoms of central nervous system Patients with second malignancies in addition to multiple myeloma Active hepatitis B or C, HIV infections Any other active diseases could affect the enrollment of this trial Suffering severe cardiovascular or respiratory disease Poorly controlled hypertension Long term use of immunosuppressive agents after organ transplantation, except currently receiving or recently received glucocorticoid treatment A history of mental illness and poorly controlled Screening showing target cell transduction efficacy is lower than 30%, or T cell proliferation is not enough for infusion (less than 5 fold) Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment Women of child-bearing potential who are pregnant or breastfeeding during therapy, or have a planned pregnancy with 2 months after therapy Women of child-bearing potential who are not willing to practice birth control from the time of enrollment on this study and for 2 months after receiving the preparative regimen. Women of child bearing potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion Active systemic infections or uncontrolled infection within 14 days prior enrollment Subjects suffering disease affects the understanding of informed consent or complying with study protocol.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: anti-BCMA CAR-T<br>Administration of anti-BCMA CAR-T cells to patients with multiple myeloma | Biological: Anti-BCMA CAR-T cells<br>* Retroviral vector-transduced autologous T cells to express anti-BCMA CAR<br>Drug: Fludarabine<br>* 30mg/m2/d<br>Drug: Cyclophosphamide<br>* 300mg/m2/d<br>|
| Experimental: anti-BCMA CAR-T+ Immune inhibitors<br>Administration of anti-BCMA CAR-T cells + Immune inhibitors to patients with multiple myeloma | Biological: Anti-BCMA CAR-T cells<br>* Retroviral vector-transduced autologous T cells to express anti-BCMA CAR<br>Drug: Fludarabine<br>* 30mg/m2/d<br>Drug: Cyclophosphamide<br>* 300mg/m2/d<br>Drug: Immune inhibitors<br>* Immune inhibitors<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 5.0 | Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 5.0 | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm | Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm | 8 weeks | 
| Duration of CAR-positive T cells in circulation | Duration of CAR-positive T cells in circulation | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BCMA, CAR-T, multiple myeloma, Relapsed /Refractory