Trials / Recruiting
RecruitingNCT05052528
Fludarabine and Cyclophosphamide With or Without Rituximab Before CD19 Chimeric Antigen Receptor T Cells for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma
A Phase I Study to Evaluate the Safety of Escalating Doses of Lymphodepleting Conditioning Chemotherapy Prior to CD19 Chimeric Antigen Receptor T Cells in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma
- Status
- Recruiting
- Phase
- Phase 1
- Study type
- Interventional
- Enrollment
- 36 (estimated)
- Sponsor
- Mehrdad Abedi, MD · Academic / Other
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
Summary
This phase I trial evaluates the best dose, possible benefits and/or side effects of fludarabine and cyclophosphamide with or without rituximab before CD19 chimeric antigen receptor T cells in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or has not responded to previous treatment (refractory). T-cells are a normal part of the immune system. To make the T-cell medication, T-cells are taken from the blood and altered in a laboratory. They are then returned to the body. The altered T-cells will latch on to a specific part of the cancer cells and hopefully kill them. Once the T-cells have been altered in the laboratory, they are called "CAR T-cells." CAR is short for "chimeric antigen receptors." These are structures on the surface of cells that allow the altered T-Cells to find and destroy the cancer cells. Another part of the T-Cell medication is called "CD19." This part is called a "biomarker." Biomarkers help doctors determine whether a cancer is getting worse and whether medications are working to stop it. The chemotherapy drugs that are given before the T-Cell therapy are cyclophosphamide, fludarabine and rituximab. Rituximab is an immunotherapy drug. These chemotherapy drugs will reduce the number of normal (unaltered) T-Cells in the body to make room for the altered T-cells to kill the cancer cells. Giving fludarabine and cyclophosphamide with or without rituximab before CD19 CAR T cell therapy may help improve response to CD19 CAR T cell therapy in patients with diffuse large B-cell lymphoma.
Detailed description
PRIMARY OBJECTIVES:I. To examine the feasibility to manufacture autologous CD19 CAR T cells at a minimum target dose of 1.0 x 10\^6 cells/kilogram using the CliniMACS automated system.II. To determine the safety of administering high-dose conditioning chemotherapy with cyclophosphamide and fludarabine with rituximab prior to CD19 CAR-T cell therapy in patients with relapsed (R)/refractory (R) diffuse large B cell lymphoma (DLBCL) and to find the recommended regimen after phase II dose for this therapy.III. To determine the safety of infusion of chimeric antigen receptor T cells targeting CD19 in adults with R/R DLBCL. SECONDARY OBJECTIVES:I. To describe the toxicities related to CD19 targeted CAR T cells.II. To describe the overall response rate (ORR) and complete response (CR) rate of relapsed DLBCL treated with CD19 CAR T cells.III. To assess other response variables including overall survival (OS), progression free survival (PFS), and event free survival (EFS). OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 6 dose levels. DOSE LEVEL 1: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes daily and cyclophosphamide IV over 60 minutes daily on days -5 to -3. Patients also receive CD19 CAR T cells IV on day 0. DOSE LEVEL 2: Patients receive rituximab IV on day -5, fludarabine phosphate IV over 30 minutes daily on days -5 to -3, and cyclophosphamide IV over 60 minutes on days -5 to -3. Patients also receive CD19 CAR T cells IV on day 0. DOSE LEVEL 3: Patients receive fludarabine phosphate IV over 30 minutes daily on days -3 to -5 and cyclophosphamide IV over 60 minutes daily on day -5. Patients also receive CD19 CAR T cells IV on day 0.DOSE LEVEL 4: Patients receive rituximab IV on day -5, fludarabine phosphate IV over 30 minutes daily on days -5 to -3, and cyclophosphamide IV over 60 minutes on day -5. Patients also receive CD19 CAR T cells IV on day 0. DOSE LEVEL 5: Patients receive fludarabine phosphate IV over 30 minutes daily on days -5 to -1 and cyclophosphamide IV over 60 minutes daily on days -5 and -4. Patients also receive CD19 CAR T cells IV on day 0. DOSE LEVEL 6: Patients receive rituximab IV on day -5, fludarabine phosphate IV over 30 minutes daily on days -5 to -1, and cyclophosphamide IV over 60 minutes on days -5 and -4. Patients also receive CD19 CAR T cells IV on day 0.After completion of study treatment, patients are followed up at 30, 60, and 90 days, 6 and 12 months, and then annually for up to 15 years.
Conditions
Interventions
| Type | Name | Description |
|---|---|---|
| BIOLOGICAL | Chimeric Antigen Receptor T-Cell Therapy | Given CD19 CAR T cells IV |
| DRUG | Cyclophosphamide | Given IV |
| DRUG | Fludarabine Phosphate | Given IV |
| BIOLOGICAL | Rituximab | Given IV |
Timeline
- Start date
- 2021-09-17
- Primary completion
- 2025-05-15
- Completion
- 2025-12-15
- First posted
- 2021-09-22
- Last updated
- 2024-05-13
Locations
1 site across 1 country: United States
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT05052528. Inclusion in this directory is not an endorsement.