CS1-CAR T Therapy Following Chemotherapy in Treating Patients With Relapsed or Refractory CS1 Positive Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT03710421|
Recruitment Status : Recruiting
First Posted : October 18, 2018
Last Update Posted : November 17, 2021
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma||Procedure: CS1-CAR T Therapy Drug: Cyclophosphamide Drug: Fludarabine Procedure: Leukapheresis||Phase 1|
I. To evaluate the safety and tolerability of intravenous (i.v.) delivered autologous CS1-CAR T cells for research participants with CS1+ recurrent/refractory multiple myeloma (MM).
I. Evaluate the response rates at days 28, 100, and 180 post CAR T cell infusion.
II. Measure the persistence of CS1-CAR T cells in blood and marrow. III. Measure phenotype and anti-tumor functionality of CS1-CAR T cells in marrow and blood.
IV. Measure the levels of cytokines in blood and marrow, and soluble CS-1 in blood post infusion as a surrogate indicator of CAR T cell activity.
V. Evaluate CS-1 expression on MM cancer cells before, during and at progressive disease (PD) to determine antigenic loss.
I. Describe the percentage of MM cells that express CS-1 surface marker before, during and at PD.
OUTLINE: This is a dose-escalation study of CS1-CAR T cells.
Patients undergo leukapheresis over 2-4 hours. Beginning 3-4 weeks, patients receive cyclophosphamide intravenously (IV) on days -4 and/or -3 or fludarabine IV and cyclophosphamide IV on days -5 to -3. Patients then undergo CS1-CAR T therapy over 10-15 minutes on day 0.
After completion of study treatment, patients are followed up at 1 day, at least every 2 days for up to a minimum of 14 days, weekly for 1 month, monthly for 1 year, then periodically for up to 15 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study to Evaluate Cellular Immunotherapy Using Memory-Enriched T Cells Lentivirally Transduced to Express a CS1-Targeting, Hinge-Optimized, 41BB-Costimulatory Chimeric Antigen Receptor and a Truncated EGFR Following Lymphodepleting Chemotherapy in Adult Patients With CS1+ Multiple Myeloma|
|Actual Study Start Date :||February 13, 2019|
|Estimated Primary Completion Date :||December 10, 2023|
|Estimated Study Completion Date :||December 10, 2023|
Experimental: Treatment (leukapheresis, chemotherapy, CS-1 CAR T therapy)
Patients undergo leukapheresis over 2-4 hours. Beginning 3-4 weeks, patients receive cyclophosphamide IV on days -4 and/or -3 or fludarabine IV and cyclophosphamide IV on days -5 to -3. Patients then undergo CS1-CAR T therapy over 10-15 minutes on day 0.
Procedure: CS1-CAR T Therapy
Undergo CS1-CAR T therapy
Other Name: Fluradosa
- Incidence of dose-limiting toxicity (DLT) and all other toxicities [ Time Frame: Up to 12 months ]Tables will be created to summarize all toxicities and side effects by organ, severity (Common Terminology Criteria for Adverse Events version 5.0), and attribution. Rates and associated 90% confidence limits will be estimated for participants experiencing DLTs.
- Incidence of all other toxicities [ Time Frame: Up to 15 years ]Will be assessed by Common Terminology Criteria for Adverse Events version 5.0. Will include cytokine release syndrome (CRS) based on the revised CRS grading system, and heart failure based on New York Heart Association criteria.
- Opportunistic infections [ Time Frame: Up to 15 years ]
- Prolonged lymphopenia (lasting more than 12 weeks) [ Time Frame: Up to 15 years ]
- Disease response [ Time Frame: Up to 180 days ]Disease status will be evaluated based on the International Myeloma Working Group for Multiple Myeloma. Descriptive statistics will be provided for patient demographics, phenotype and functionality of modified T cells as well as anti-tumor immune response.
- Expansion/persistence of chimeric antigen receptor (CAR) T cells [ Time Frame: At 28 days post CAR T cell infusion ]Rates and associated 90% confidence limits will be estimated for participants achieving persistence/expansion of T cells at 28 days. To further study T cell expansion and persistence, area under the curve of log10 copies/ug of genomic deoxyribonucelic acid over the 28 day period post T cell infusion will be calculated for each participant and presented both graphically and using descriptive statistics.
- Phenotype and anti-tumor functionality of modified T cells in marrow and blood [ Time Frame: Up to 15 years ]Descriptive statistics will be provided for patient demographics, phenotype and functionality of modified T cells as well as anti-tumor immune response.
- Cytokine and soluble CS-1 levels in blood and marrow [ Time Frame: Up to 15 years ]Statistical and graphical methods will be used to describe the cytokine levels (marrow and blood) over the study period.
- Disease free survival (DFS) [ Time Frame: At 12 months ]Rates and associated 90% confidence limits will be estimated for participants experiencing DFS. Kaplan Meier methods will be used to describe the survival distributions both statistically and graphically.
- Progression-free survival [ Time Frame: At 12 months ]Kaplan Meier methods will be used to describe the survival distributions both statistically and graphically.
- CS1 expression on multiple myeloma cells [ Time Frame: Baseline up to 15 years ]
- MM cells that are CS-1 positive [ Time Frame: Up to 15 years ]Descriptive statistics are provided for the percentage of MM cells that express CS-1 surface marker.
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): NCT03710421
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Myo Htut 626-218-2405 email@example.com|
|Principal Investigator: Myo Htut|
|Principal Investigator:||Myo Htut||City of Hope Medical Center|