BCMA-Specific CAR T-Cells Combined With a Gamma Secretase Inhibitor (JSMD194) to Treat Relapsed or Persistent Multiple Myeloma

Summary

This phase I trial determines the side effects and best dose of B-cell maturation antigen (BCMA)-chimeric antigen receptor (CAR) T-cells when combined with gamma-secretase inhibitor LY3039478 (JSMD194), cyclophosphamide, and fludarabine in treating participants with multiple myeloma that that has come back or remains despite treatment. Placing genes added in the laboratory into immune T-cells may make the T-cells recognize BCMA, a protein on the surface of cancer cells. JSMD194 may enhance the killing of cancer cells by increasing the BCMA expression on multiple myeloma cells, making the targeted BCMA CAR-T treatment more effective. JSMD194 also decreases the amount of BCMA found in the circulation (called soluble BCMA) that is not bound to the myeloma cells. JSMD194 can therefore reduce the potential for soluble BCMA to act as a decoy. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving BCMA CAR T therapy with JSMD194, cyclophosphamide, and fludarabine may work better in treating participants with relapsed or persistent multiple myeloma.

Conditions

• Recurrent Plasma Cell Myeloma
• Refractory Plasma Cell Myeloma

Interventions

BIOLOGICAL

BCMA-specific CAR-expressing T Lymphocytes

Receive CAR T infusion

DRUG

Cyclophosphamide

Given IV

DRUG

Fludarabine

Given IV

DRUG

Gamma-Secretase Inhibitor LY3039478

Given PO

OTHER

Laboratory Biomarker Analysis

Correlative studies

OTHER

Pharmacokinetic Study

Correlative studies

Sponsors & Collaborators

• Juno Therapeutics, Inc., a Bristol-Myers Squibb Company

  collaborator INDUSTRY

• The Leukemia and Lymphoma Society

  collaborator OTHER

• Fred Hutchinson Cancer Center

  lead OTHER

Principal Investigators

• Andrew Cowan · Fred Hutch/University of Washington Cancer Consortium

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-05-23

Primary Completion

2022-04-20

Completion

2022-04-20

FDA Drug

Yes

Countries

• United States

Study Locations