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

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

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

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: clarithromycin, lenalidomide, dexamethasone and autologous BCMA-directed CAR T-cells

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xiaowen Tang, Ph.D; Phone Number: 86-512677801856; Email: xwtang1020@163.com
• Study Contact Backup: Name: Depei Wu, Ph.D; Phone Number: 86-512677801856; Email: drwudepei@163.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: Xiaowen Tang, Ph.D; Phone Number: 86-512677801856; Email: xwtang1020@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Newly diagnosed MM according to the criteria by International Myeloma Working Group (IMWG)
2. Age 18-75
3. Eastern Cooperative Oncology Group (ECOG) score 0-2
4. BCMA positive as detected with flowcytometry or ELISA.
5. Patients with left ventricular ejection fraction ≥ 0.5 by echocardiography or grade I/II cardiovascular dysfunction according to the New York Heart Association Classification.
6. Patients with aspartate aminotransferase or glutamic-pyruvic transaminase > 3x upper limit of normal or bilirubin > 2.0 mg/dL

Exclusion Criteria:

1. Patients are pregnant or lactating.
2. Nonsecretory MM.
3. History of previous treatment of MM.
4. Patients with uncontrolled active infection.
5. Patients with active hepatitis B or hepatitis C infection.
6. Patients with HIV infection.
7. Patients with atrial or venous thrombosis or embolism.
8. Patients with myo-infarction or severe arrythmia in the recent 6 months.
9. Other comorbidities that investigators considered not suitable for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BiRd combined with BCMA CAR T-cells infusion	Drug: clarithromycin, lenalidomide, dexamethasone and autologous BCMA-directed CAR T-cells; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; Jiangsu Province Hospital of Traditional Chinese Medicine; Affiliated Hospital of Jiangnan University; The Second People's Hospital of Huai'an; Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd; Jiangyin People's Hospital; Suzhou Municipal Hospital; Jingjiang People's Hospital; Changshu Frist People's Hospital; The Third People's Hospital of Kunshan; Lianyungang Hospital Affiliated Bengbu Medical College; Zhangjiagang First People's Hospital; The first Affiliated Hospital of Nanjing University Medical School

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2017
• Primary Completion (Anticipated): January 31, 2023
• Study Completion (Anticipated): January 31, 2025

Study Registration Dates

• First Submitted: February 19, 2020
• First Submitted That Met QC Criteria: February 25, 2020
• First Posted (Actual): February 27, 2020

Study Record Updates

• Last Update Posted (Actual): October 25, 2021
• Last Update Submitted That Met QC Criteria: October 22, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: MM; BCMA; CART; BiRd
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Dexamethasone; Lenalidomide; Clarithromycin
• Other Study ID Numbers: BiRd-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No