Trials / Recruiting
RecruitingNCT07340853
CRISPR Delivered Anti-BCMA Car-T Therapy for Relapsed or Refractory Multiple Myeloma
A Phase 1b Clinical Trial of CRISPR Delivered Anti-BCMA Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Multiple Myeloma
- Status
- Recruiting
- Phase
- Phase 1
- Study type
- Interventional
- Enrollment
- 30 (estimated)
- Sponsor
- Thomas Martin, MD · Academic / Other
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
Summary
This phase Ib trial tests the safety, side effects and best dose of clustered regularly interspaced short palindromic repeats (CRISPR) delivered anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cells (1XX BCMA CAR-T cells) in treating patients with multiple myeloma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Anti-BCMA CAR-T cell therapy is a type of treatment in which a person'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, such as BCMA, on the patient's cancer cells is added to the T cells in the laboratory by a tool called clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9. The special receptor is called a 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. Giving chemotherapy before CAR-T cells may decrease the number of lymphocytes (a type of white blood cells) in the blood and may help the 1XX BCMA CAR-T cells fight the cancer cells. Treatment with 1XX BCMA CAR-T cells may be safe, tolerable, and/or effective in treating patients with relapsed or refractory multiple myeloma (RRMM).
Detailed description
PRIMARY OBJECTIVES: Dose Escalation: I. To evaluate the safety and toxicity of administering Chimeric Antigen Receptor T Cells (CAR-T) cells targeting BCMA to participants with Relapsed or Refractory Multiple Myeloma (RRMM). II. To determine the maximum tolerated dose (MTD) for anti-BCMA CAR-T cells. Dose Expansion: III. Determine whether administering conforming CAR T-cell product targeting BCMA to participants with RRMM increases the overall response rate (ORR) compared with historical data for non-CAR agents per International Myeloma Working Group (IMWG) response criteria. IV. Determine whether administering conforming CAR T-cell product targeting BCMA to participants with RRMM lowers the Grade 2 or greater neurologic events to \<10% in RRMM. SECONDARY OBJECTIVES: Dose Expansion: I. To describe the efficacy of conforming CAR-T cell product targeting BCMA in participants with RRMM. II. To evaluate the feasibility of manufacturing anti-BCMA CAR T-cells locally and ability to produce adequate quantities of vector positive T-cells. III. To evaluate the safety and toxicity of conforming CAR-T cell product targeting BCMA to participants with RRMM. EXPLORATORY OBJECTIVES: I. To determine the degree and impact of CAR-T persistence following anti-BCMA CAR-T cell infusion, on clinical outcomes and safety. II. Describe changes in health-related quality of life (HRQoL) using the European Organization for Research and Treatment of Cancer - Quality of Life C30 questionnaire (EORTC-QLQ-C30). III. To describe the efficacy of CAR-T cells targeting BCMA in participants with relapsed or refractory BCMA+ RRMM who were treated with product that did not meet one or more pre-specified release criteria (non-conforming product cohort). OUTLINE: Participants in both cohorts will undergo leukapheresis, receive lymphodepleting chemotherapy and then receive a single infusion of BCMA CAR-T therapy. After completion of study treatment, participants are followed up at 30, 60 and 90 days, 6 and 12 months, and then yearly for up to 15 years.
Conditions
Interventions
| Type | Name | Description |
|---|---|---|
| PROCEDURE | Leukapheresis | Undergo Leukapheresis |
| DRUG | Cyclophosphamide | Given Intravenously (IV) |
| BIOLOGICAL | Chimeric Antigen Receptor T cells (CAR-T) Targeting BCMA | Given Intravenously (IV) |
| BEHAVIORAL | Quality of Life (QoL) Questionnaires | Ancillary studies |
| PROCEDURE | Bone Marrow Biopsy | Undergo biopsy |
| BIOLOGICAL | Biospecimen Collection | Undergo Blood, serum and urine collection |
| DRUG | Fludarabine | Given IV |
| PROCEDURE | Radiographic imaging | Undergo radiographic imaging |
Timeline
- Start date
- 2026-02-28
- Primary completion
- 2028-05-25
- Completion
- 2043-05-25
- First posted
- 2026-01-14
- Last updated
- 2026-03-10
Locations
1 site across 1 country: United States
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT07340853. Inclusion in this directory is not an endorsement.