Study of BiRd Regimen Combined With BCMA CAR T-cell Therapy in Newly Diagnosed Multiple Myeloma (MM) Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of BiRd regimen combined with BCMA CAR T cell therapy in newly diagnosed multiple myeloma patients

Detailed Description
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This is a phase 3, single arm, multi-center study. The patients will receive BiRd regimen (clarithromycin,lenalidomide, dexamethasone) combined with infusion of autologous BCMA-directed CAR T-cells in newly diagnosed MM patients. The study participation will be 4 years including treatment and follow-up periods.

Official Title
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A Phase 3, Single Arm, Multi-Center Study to Assess the Efficacy and Safety of Clarithromycin(Biaxin)-Lenalidomide-Low-Dose-Dexamethasone (BiRd) Combined With B-cell Maturation Antigen (BCMA)-Directed Chimeric Antigen Receptor (CAR) T-cell Therapy in Patients With Newly Diagnosed Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: clarithromycin, lenalidomide, dexamethasone and autologous BCMA-directed CAR T-cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed MM according to the criteria by International Myeloma Working Group (IMWG) Age 18-75 Eastern Cooperative Oncology Group (ECOG) score 0-2 BCMA positive as detected with flowcytometry or ELISA. Patients with left ventricular ejection fraction ≥ 0.5 by echocardiography or grade I/II cardiovascular dysfunction according to the New York Heart Association Classification. Patients with aspartate aminotransferase or glutamic-pyruvic transaminase > 3x upper limit of normal or bilirubin > 2.0 mg/dL Exclusion Criteria: Patients are pregnant or lactating. Nonsecretory MM. History of previous treatment of MM. Patients with uncontrolled active infection. Patients with active hepatitis B or hepatitis C infection. Patients with HIV infection. Patients with atrial or venous thrombosis or embolism. Patients with myo-infarction or severe arrythmia in the recent 6 months. Other comorbidities that investigators considered not suitable for this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: BiRd combined with BCMA CAR T-cells infusion<br> | Drug: clarithromycin, lenalidomide, dexamethasone and autologous BCMA-directed CAR T-cells<br>* clarithromycin: 500mg, PO, twice daily, on days 1 21 for a 28-day cycle. lenalidomide: 25mg, PO, on days 1 21 for a 28-day cycle. dexamethasone: 40mg, PO on days 1,8,15 and 22 for a 28-day cycle. BCMA CAR T cell: (2-3)×10E7/kg, intravenously infusion. Doses should be adjusted according to renal function.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | ORR includes stringent complete response (sCR), complete remission (CR), very good partial remission (VGPR) and partial remission (PR). Stringent complete response (sCR): complete response as defined below plus normal free light chain (FLC) and absence of clonal cells in bone marrow biopsy by immunohistochemistry (κ/λ ratio ≤4:1 or ≥1:2 for κ and λ patients, respectively, after counting ≥100 plasma cells). Complete Response (CR)：negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow aspirates. Very good partial response (VGPR)：serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 h. Partial response (PR): ≥50% reduction of serum M-protein plus reduction in 24 h urine M-protein by ≥90% or to <200 mg per 24 h. | 4 weeks after CAR T-cells infusion (up to 14 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | time from enrollment to the date of death from any cause | 4 years | 
| Event-free survival (EFS) | time from enrollment to the date of primary refractory disease, or relapse from sCR, or CR, or death from any cause | 4 years | 
| Cumulative incidence of relapse(CIR) | time from the date of achievement of a remission until the date of relapse | 4 years | 
| Number of adverse events | adverse events are evaluated with CTCAE V5.0 | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BiRd, CART, BCMA, MM