NCT03502577

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

A Phase I Study of B-Cell Maturation Antigen (BCMA)-Specific Chimeric Antigen Receptor T Cells in Combination With JSMD194, a Small Molecule Inhibitor of Gamma Secretase, in Patients With Relapsed or Persistent Multiple Myeloma

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 19 (actual)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

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.

Detailed description

OUTLINE: This is a dose escalation study of BCMA-specific CAR T-cells. Participants receive fludarabine and cyclophosphamide on days -4 to -2. Participants then receive BCMA-specific CAR T-cells intravenously (IV) over 20-30 minutes on day 0 and gamma-secretase inhibitor LY3039478 orally (PO) on days 2, 4, 7, 9, 11, 14, 16, and 18. Patients will also receive JSMD194 orally before the fludarabine and cyclophosphamide to evaluate the effect of this drug alone on multiple myeloma cell BCMA levels. After completion of study treatment, participants are followed up every 6 months for years 1-5 and annually for years 6-15.

Conditions

• Recurrent Plasma Cell Myeloma
• Refractory Plasma Cell Myeloma

Interventions

Type	Name	Description
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

Timeline

• Start date: 2018-05-23
• Primary completion: 2022-04-20
• Completion: 2022-04-20
• First posted: 2018-04-18
• Last updated: 2024-01-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study