CAR-T Re-treatment for Refractory/Relapsed Multiple Myeloma

Study of CAR-T Cells Targeting BCMA for Previously CAR-T Treated Refractory/Relapsed Multiple Myeloma

This is a single arm, open-label, single-center, phase 1 study, to determine the safety and efficacy of autologous reinfusion of CAR-T cells targeting BCMA in the treatment of refractory/relapsed multiple myeloma (r/r MM) who get recurrence and progression after previous CAR-T cell therapy.

Study Overview

• Status: Unknown
• Conditions: Multiple Myeloma; Multiple Myeloma in Relapse; Multiple Myeloma Progression
• Intervention / Treatment: Drug: CAR-T Re-treatment

• Study Type: Interventional
• Enrollment (Anticipated): 20
• 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 and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must have a confirmed prior diagnosis of active multiple myeloma as defined by the updated IMWG criteria.
2. 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.
3. Refractory disease：1) At least 3 prior regimens, which must at least have contained bortezomi. or 2) other circumstances identified by clinical doctors.
4. Relapse criteria in NCCN clinical practice guidelines in Oncology: Multiple Myeloma (2016.V2).

Exclusion Criteria:

1. Women of child-bearing potential or who are pregnant or breastfeeding.
2. Have any active and uncontrolled infection: hepatitis B, hepatitis C, HIV, or other fatal viral and bacterial infection.
3. 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.
4. Patients with any uncontrolled intercurrent illness or serious uncontrolled medical disorder.
5. Patients with CNS metastases or symptomatic CNS involvement (including cranial neuropathies or mass lesions and spinal cord compression).
6. 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.
7. Patients with active autoimmune skin diseases such as psoriasis or other active autoimmune diseases such as rheumatoid arthritis.
8. other conditions that excluded by clinicians.

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: CAR-T Re-treatment group; Patients will be treated with CAR-T cells targeting BCMA (Different epitope with the previous CAR-T cell treatment they had been used) with a escalation approach, 0.5x10^6- 2.0x10^6 CAR-T cells/kg.

Drug: CAR-T Re-treatment; Patients will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) or use their mononuclear cells that preserved in the laboratory for the production of CAR-T cells. After a pre-treatment lymphodepletion therapy, patients will receive the re-treatment of CAR-T therapy by intravenous injection.; Other Names: CAR-T Re-treatment for r/r MM targeting BCMA

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, >= Grade 1 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment	Day 1-30 days after injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-myeloma responses	by measuring the changes of aberrant immunoglobulin in serum	Day 1-60 months
Anti-myeloma responses	multiple myeloma cells in bone marrow	Day 1-60 months

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 13, 2018
• First Submitted That Met QC Criteria: September 13, 2018
• First Posted (Actual): September 14, 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: CAR-T re-treatment-MM

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