Last reviewed · How we verify
A Phase 1 Single Arm, Open Label Study to Evaluate the Safety of UF-KURE-BCMA CAR-T Cells in Patients With Relapsed or Refractory Multiple Myeloma
The purpose of this study is to determine if UF-KURE-BCMA (B-Cell Maturation Antigen) chimeric antigen receptor T cells (CAR-T cells) can be used to treat relapsed or treatment refractory multiple myeloma (RRMM). This treatment uses T cells already present within the body that have been modified outside of the body by a virus and then returned by an infusion to fight cancer. The investigators are evaluating UF-KURE-BCMA because it uses a manufacturing process that is shorter than other Food and Drug Administration (FDA) approved CAR-T cells and only requires a simple blood draw. The standard treatments require weeks to manufacture the cells as well a special procedure to get an individual's cells. While the shorter manufacture time can be an advantage, the safety of this approach has not been demonstrated. The use of UF-KURE-BMCA is investigational and is not approved by the FDA outside of clinical trials. This is the first study of UF-KURE-BCMA in patients. Participants will give a pint of blood, which is the amount one would provide if they were to donate blood. The blood will be used to make the UF-KURE-BCMA cells. Participants will then receive chemotherapy followed by a one-time infusion of the experimental modified CAR-T cells. After this infusion, participants will be watched for side effects and follow up will continue for up to 15 years.
Details
| Lead sponsor | David Wald |
|---|---|
| Phase | Phase 1 |
| Status | WITHDRAWN |
| Start date | 2025-09 |
| Completion | 2028-09 |
Conditions
- Multiple Myeloma
- Multiple Myeloma in Relapse
- Multiple Myeloma, Refractory
Interventions
- UF-KURE-BCMA CAR T-cells
- Cyclophosphamide
- Fludarabine
Primary outcomes
- To recommend a phase two cell dose for UF-KURE-BCMA. — 28 days
Patients will be enrolled sequentially using a 3+3 design no sooner than every 28 days during the dose escalation phase and monitored for excessive dose limiting toxicities (DLT). If more than one DLT is observed in 6 patients treated, that dose is considered too toxic. The following serious adverse events are deemed DLTs. DLTs are graded per CTACAE V5 or ASTCT grading for CRS or ICANS. * Any death unless due to disease progression * Grade 4 CRS. * Grade 3 CRS that does not improve to ≤ grade 2 in 72 hours after treatment. * Grade 3 or higher ICANS. * Grade 4 neutropenia or thrombocytopenia that does not improve to ≤ Grade 2 within 42 days. Grade 3 thrombocytopenia with clinically significant bleeding. * Grade 3 or higher organ toxicity of any duration (Exception Grade 3 or 4 abnormal hepatic or renal function tests that improve to ≤ Grade 2 within 7 days). * All other Grade 3 toxicities, not attributable to disease or chemo that do not resolve to ≤ Grade 2 within 72 hours. - Incidence of trial stopping rule event — 28 days
In the event of any of the following, study enrollment will be suspended pending safety review. 1. Any treatment-related death (Grade 5 event) that occurs following treatment with UF-KURE-BCMA T cells and not related to disease progression. 2. Unexpected severe toxicities such as 1. Occurrence of Grade 4 DLTs in 2 subjects at the same dose level. 2. Uncontrolled CAR T cell proliferation requiring CAR T cell ablation. 3. Grade 4 neurotoxicity with cerebral edema. 4. New malignancy distinct from recurrence/progression of previously treated malignancy and at least possibly related to IP. 5. Replication-competent lentivirus (RCL) detection in any subjects. To re-initiate study enrollment, the sponsor and principal investigator will submit a study reactivation plan to the Food and Drug Administration for approval, including additional safeguards to prevent and minimize subsequent adverse events.
Countries
United States