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CART-BCMA/CS1 in Treating Patients With Relapsed or Refractory Multiple Myeloma
Phase I Dose-Escalation Study of BCMA/CS1 Bispecific Chimeric Antigen Receptor (CAR)-T Cells for Relapsed/Refractory Multiple Myeloma
2 other identifiers
interventional
N/A
1 country
1
Brief Summary
This phase I trial studies the side effects and how well CART-BCMA/CS1 works in treating patients with multiple myeloma (MM) that has come back (relapsed) or that does not respond to treatment (refractory). Chimeric antigen receptor (CAR) T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers, including MM. Immune cells can be engineered to kill MM cells by inserting a piece of deoxyribonucleic acid (DNA) into the immune cells using a lentiviral vector, that allows them to recognize MM cells. CART-BCMA cells are such modified T cells that target markers called CS1 or B-cell maturation antigen (BCMA), which is expressed by a type of white blood cell called a "B-cell", which are cells that may help the MM cells grow. These engineered CART-BCMA/CS1 cells may kill MM cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started Mar 2024
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 10, 2023
CompletedFirst Posted
Study publicly available on registry
July 18, 2023
CompletedStudy Start
First participant enrolled
March 28, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 28, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 28, 2028
May 1, 2024
April 1, 2024
3 years
July 10, 2023
April 30, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Incidence of dose limiting toxicities (DLTs)
Will be assessed by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v. 5). For cytokine release syndrome (CRS) and neurotoxicity, patients will be evaluated using the grading criteria outlined by the American Society for Transplantation and Cellular Therapy (ASTCT).
Within 28 days from CART-BCMA/CS1 cell infusion
Secondary Outcomes (7)
Incidence of adverse events
Up to 15 years
Clinical response rate
Up to 2 years
Overall response rate
Up to 2 years
Duration of response
Up to 2 years
Overall survival
The date of CART-BCMA/CS1 cell infusion in the study until death, assessed up to 15 years
- +2 more secondary outcomes
Study Arms (1)
Treatment (CART-BCMA/CS1)
EXPERIMENTALPatients undergo leukapheresis on 35 to 21 days before Infusion Day (I-Day -35 to I-Day -21) and receive cyclophosphamide IV over 60 minutes and fludarabine IV over 30 minutes on I-Days -5, -4, and -3. Patients then receive CART-BCMA/CS1 IV on I-Day-0 on study. Patients undergo ECHO, ECG and MRI during screening. Patients undergo bone marrow biopsy and/or bone marrow aspirate screening, between I-Day -28 to I-Day -5, I-Day 30, and at 1 year post CART-BCMA/CS1 infusion. Patients also undergo FDG PET/CT during screening, between I-Day -28 to I-Day -5, I-Day 90 and I-Day 180 and every 3 months thereafter.
Interventions
Undergo bone marrow biopsy and aspiration
Undergo PET/CT
Receive IV
Receive IV
Receive CART-BCMA/CS1 cells IV
Undergo leukapheresis
Undergo MRI
Undergo PET/CT
Eligibility Criteria
You may qualify if:
- Diagnosis of multiple myeloma relapsed or refractory after at least three prior lines of therapy, including:
- A proteasome inhibitor and immunomodulatory agent either alone or in combination
- Anti-CD38 (Cluster of Differentiation 38) directed therapy
- Patients previously treated with anti-BCMA directed therapy are allowed onto the study. Patients must not have a history of grade \> 3 CRS or grade \>= 3 immune effector cell associated neurotoxicity (ICANS) with prior anti-BCMA therapy
- Patients must have measurable MM as defined by at least one of the criteria below:
- Serum M-protein \>= 0.5 g/dl (5 g/L)
- Urine M-protein \>= 200 mg/24 h
- Serum free light chain (FLC) assay: involved FLC level \>= 10 mg/dl (100 mg/l) provided serum FLC ratio is abnormal
- A biopsy-proven plasmacytoma
- Age \>= 18 years old and =\< 74 years old
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Absolute neutrophil count (ANC) \>= 1 x 10\^9 cells/L. Granulocyte colony stimulating factor is permitted (within 30 days prior to enrollment using standard phase I criteria for organ function)
- Platelets \>= 50 x 10\^9/L. Without transfusion, growth factors may be used to achieve eligibility criteria (within 30 days prior to enrollment using standard phase I criteria for organ function)
- Hemoglobin \>= 8 g/dL (with or without transfusion) (within 30 days prior to enrollment using standard phase I criteria for organ function)
- Aspartate and alanine aminotransferases (AST, ALT) =\< 2.5 x upper limit of normal (ULN) (within 30 days prior to enrollment using standard phase I criteria for organ function)
- +4 more criteria
You may not qualify if:
- Inability to purify \>= 5 x 10\^8 CD62L-enriched cells from leukapheresis product
- Previously known hypersensitivity to any of the agents used in this study; known sensitivity to cyclophosphamide or fludarabine
- Received systemic treatment for multiple myeloma, including immunotherapy, within 14 days prior to initiation of lymphodepletion chemotherapy administration within this protocol. Consistent with current trials, patients may otherwise be given bridging therapy at the discretion of the lead study investigator
- Prior allogeneic hematopoietic stem cell transplantation
- Autologous hematopoietic stem cell transplantation within 12 weeks prior to enrollment. Patients who have received an autologous transplant over 12 weeks from enrollment will not be excluded and may participate in the trial
- Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or having received systemic steroids within the last 2 weeks prior to enrollment (inhaled or topical steroids at standard doses are allowed)
- Human immunodeficiency virus (HIV) seropositivity or other congenital or acquired immune deficiency state, which would increase the risk of opportunistic infections and other complications during chemotherapy-induced lymphodepletion. If there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
- Hepatitis B or C seropositivity with evidence of ongoing liver damage, which would increase the likelihood of hepatic toxicities from the lymphodepletion chemotherapy regimen and supportive treatments. Patients with hepatitis C seropositive disease but undetectable hepatic C virus (HCV) ribonucleic acid (RNA) viral load will be allowed in the trial. Patients with B seropositivity on antiviral therapy will be allowed in the trial
- Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol
- Oxygen saturation of =\< 92% on room air
- A left ventricular ejection fraction =\< 45%
- Pregnancy or breast-feeding. Female patients must be surgically sterile or be postmenopausal for two years or must agree to use effective contraception during the period of treatment and for 6 months afterwards. All female patients with reproductive potential must have a negative pregnancy test (serum/urine) at screening and again within 14 days from starting the lymphodepletion chemotherapy. The definition of effective contraception will be based on the judgment of the study investigators. Patients who are breastfeeding are not allowed on this study
- History of other malignancy in the past 3 years with the following exceptions:
- Malignancy treated with curative intent and no known active disease
- Adequately treated non-melanoma skin cancer without evidence of disease
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Melanie Ayala Ceja
Los Angeles, California, 90095, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sarah Larson
UCLA / Jonsson Comprehensive Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 10, 2023
First Posted
July 18, 2023
Study Start
March 28, 2024
Primary Completion (Estimated)
March 28, 2027
Study Completion (Estimated)
March 28, 2028
Last Updated
May 1, 2024
Record last verified: 2024-04