LCAR-B4822M-02 Cells in Treating Relapsed/Refractory (R/R) Multiple Myeloma

This is a single arm, open-label, phase 1 study, to determine the safety and efficacy of LCAR-B4822M CAR-T cells in treating patients diagnosed with refractory/relapsed multiple myeloma (r/r MM).

Study Overview

• Status: Unknown
• Conditions: Refractory or Relapsed Multiple Myeloma
• Intervention / Treatment: Drug: LCAR-B4822M CAR-T Cell Immunotherapy

Detailed Description

Multiple myeloma (MM) is a usually incurable malignancy of plasma cells. Current therapies for multiple myeloma often cause remissions, but nearly all patients eventually relapse, there is an unmet clinical needs for these patients. B-cell maturation antigen (BCMA) is a protein expressed by normal plasma cells and the malignant plasma cells of multiple myeloma, and it was supposed to be a promising target for r/r MM.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710000
      • Second Affiliated Hospital of Xi'an JiaoTong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- Patients must have a confirmed prior diagnosis of active multiple myeloma as defined by the updated IMWG criteria.

Patients with refractory multiple myeloma. Clear BCMA expression must be detected on malignant plasma cells from either bone marrow or a plasmacytoma by flow cytometry or immunohistochemistry.

Refractory disease：1) At least 3 prior regimens, which must at least have contained bortezomi. or 2) other circumstances identified by clinical doctors.

Relapse criteria in NCCN clinical practice guidelines in Oncology: Multiple Myeloma (2016.V2)

Exclusion Criteria:

- Women of child-bearing potential or who are pregnant or breastfeeding. Have any active and uncontrolled infection: hepatitis B, hepatitis C, HIV, or other fatal viral and bacterial infection.

Systemic corticosteroid steroid therapy of greater than 5 mg/day of prednisone or equivalent dose of another corticosteroid are not allowed within 2 weeks prior to either the required leukapheresis or the initiation of the conditioning chemotherapy regimen.

Patients with any uncontrolled intercurrent illness or serious uncontrolled medical disorder.

Patients with CNS metastases or symptomatic CNS involvement (including cranial neuropathies or mass lesions and spinal cord compression).

History of allogeneic stem cell transplantation. Have active acute or chronic graft-versus-host-disease (GVHD), or require immunosuppressant medications for GVHD, within 6 months of enrollment.

Patients with active autoimmune skin diseases such as psoriasis or other active autoimmune diseases such as rheumatoid arthritis.

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: LCAR-B4822M treatment group; r/r multiple myeloma patients will be treated with LCAR-B4822M CAR-T cells with a escalation approach, 0.5x10^6- 2.0x10^6 CAR-T cells/kg.	Drug: LCAR-B4822M CAR-T Cell Immunotherapy; Patients will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of CAR-T cells. After a pre-treatment lymphodepletion therapy, patients will receive the LCAR-B4822M CAR-T Cell Immunotherapy by intravenous injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of treatment related adverse events	Assessed by CTCAE v4.0	Day 1-30 days after injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-myeloma responses to LCAR-B4822M cell treatment	by measuring the changes of aberrant immunoglobulin in serum	Day 1-36 months after injection
Anti-myeloma responses to LCAR-B38M cell treatment	multiple myeloma cells in bone marrow	Day 1-36 months after injection

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Xi'an Jiaotong University
• Collaborators: Nanjing Legend Biotech Co.
• Investigators: Principal Investigator: Wan-Hong Zhao, MD, PhD, Second Affiliated Hospital of Xi'an JiaoTong University

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2018
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: September 12, 2018
• First Submitted That Met QC Criteria: September 12, 2018
• First Posted (Actual): September 17, 2018

Study Record Updates

• Last Update Posted (Actual): December 14, 2018
• Last Update Submitted That Met QC Criteria: December 13, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• 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
• Other Study ID Numbers: LCAR-B4822M

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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