BCMA-Specific CAR T-Cells Combined With a Gamma Secretase Inhibitor (JSMD194) to Treat Relapsed or Persistent Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT03502577|
Recruitment Status : Recruiting
First Posted : April 18, 2018
Last Update Posted : April 4, 2019
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma||Biological: BCMA-specific CAR-expressing T Lymphocytes Drug: Cyclophosphamide Drug: Fludarabine Drug: Gamma-Secretase Inhibitor LY3039478 Other: Laboratory Biomarker Analysis Other: Pharmacokinetic Study||Phase 1|
I. To evaluate the safety of BCMA-targeting CAR T-cells in combination with JSMD194 for patients with relapsed or treatment refractory multiple myeloma.
II. To identify the recommended phase 2 dose (R2PD) of BCMA CAR T cells administered in combination with JSMD194 in patients with measurable tumor burden prior to T cell transfer.
I. To determine the peak concentration, in vivo persistence and the phenotype of transferred CAR T cells when administered in combination with JSMD194.
II. To estimate the antitumor activity of adoptively transferred BCMA CAR T cells when administered with JSMD194.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||May 23, 2018|
|Estimated Primary Completion Date :||July 30, 2021|
|Estimated Study Completion Date :||July 30, 2034|
Experimental: Treatment (Chemotherapy, BCMA-specific CAR T-cells, LY3039478)
Participants receive fludarabine and cyclophosphamide on days -4 to -2. Participants then receive BCMA-specific CAR T-cells IV over 20-30 minutes on day 0 and LY3039478 PO on days 2, 4, 7, 9, 11, 14, 16, and 18.
Biological: BCMA-specific CAR-expressing T Lymphocytes
Receive CAR T infusion
Other Name: Fluradosa
Drug: Gamma-Secretase Inhibitor LY3039478
Other: Laboratory Biomarker Analysis
Other: Pharmacokinetic Study
- Maximum tolerated dose (MTD) of chimeric antigen receptor (CAR) T cells [ Time Frame: Up to 28 days following CAR T-cell infusion ]This is defined as the dose associated with a true dose-limiting toxicity (DLT) rate of 25% in each of the cohorts. DLTs are events that occur within the first 28 days following CAR T-cell infusion.
- Incidence of general toxicities [ Time Frame: Up to 1 year ]This will be measured according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
- Incidence of general toxicities [ Time Frame: Up to 15 years ]This will be measured according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
- Objective response rate of complete remission and partial remission [ Time Frame: Up to 15 years ]
- Progression-free survival [ Time Frame: Up to 15 years ]
- Overall survival [ Time Frame: Up to 15 years ]
- Duration of persistence of adoptively transferred B-cell maturation antigen (BCMA) CAR T cells [ Time Frame: Baseline up to 15 years ]
- Evaluation of the migration of adoptively transferred BCMA CAR T cells [ Time Frame: Baseline up to 15 years ]
- Plasma cell BCMA expression and soluble (s)BCMA levels with LY3039478 administration [ Time Frame: Up to 1 year ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03502577
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Immunotherapy Trials Intake, SCCA 206-606-4668 firstname.lastname@example.org|
|Principal Investigator: Andrew J. Cowan|
|Principal Investigator:||Andrew Cowan||Fred Hutch/University of Washington Cancer Consortium|