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Trials / Recruiting

RecruitingNCT06191887

B-Cell Activating Factor Receptor (BAFFR)-Based Chimeric Antigen Receptor T-Cells With Fludarabine and Cyclophosphamide Lymphodepletion for the Treatment of Relapsed or Refractory B-cell Hematologic Malignancies

Phase 1a/1b Dose Escalation and Cohort Expansion Study of the Safety and Efficacy of B-Cell Activating Factor Receptor (BAFFR)-Based Chimeric Antigen Receptor T-Cells (MC10029) in Subjects With Relapsed or Refractory BAFFR-Expressing B-Cell Hematologic Malignancies

Status
Recruiting
Phase
Phase 1
Study type
Interventional
Enrollment
27 (estimated)
Sponsor
Mayo Clinic · Academic / Other
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

Summary

This phase I trial tests safety, side effects and best dose of B-cell activating factor receptor (BAFFR)-based chimeric antigen receptor T-cells, with fludarabine and cyclophosphamide lymphodepletion, for the treatment of patients with B-cell hematologic malignancies that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). BAFFR-based chimeric antigen receptor T-cells 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. Giving chemotherapy, such as fludarabine and cyclophosphamide, helps ill cancer cells in the body and helps prepare the body to receive the BAFFR based chimeric antigen receptor T-cells. Giving BAFFR based chimeric antigen receptor T-cells with fludarabine and cyclophosphamide for lymphodepletion may work better for the treatment of patients with relapsed or refractory B-cell hematologic malignancies.

Detailed description

PRIMARY OBJECTIVES: I. To assess the safety and tolerability of (MC10029) autologous BAFFR-targeting chimeric antigen receptor (CAR) T cells following lymphodepleting (LD) therapy in subjects with relapsed or refractory BAFFR expressing B-cell hematologic malignancies. II. To determine the recommended dose for phase 1b (dose expansion) and recommend phase 2 dose. SECONDARY OBJECTIVES: I. To assess the efficacy and antitumor activity of MC10029 in subjects with relapsed or refractory BAFFR-expressing B-cell hematologic malignancies. II. To determine long-term toxicities in MC10029 recipients. III. To determine feasibility of manufacturing success rate of MC10029. CORRELATIVE RESEARCH OBJECTIVES: I. To evaluate the pharmacokinetics of MC10029 in peripheral blood samples. II. To study the relationship between BAFFR expression and clinical activity of MC10029. OUTLINE: Patients undergo leukapheresis. Patients then receive cyclophosphamide intravenously (IV), over 60 minutes and fludarabine IV over 30 minutes on day -5 to -3 or bendamustine IV over 10 minutes on days -4 and -3. Patients receive BAFFR based chimeric antigen receptor T-cells IV on day 0. Patients undergo echocardiography and magnetic resonance imaging (MRI) at screening, computed tomography (CT) scan, positron emission tomography (PET) scan, bone marrow biopsy/aspirate and blood sample collection throughout the study and tumor biopsy at progression. After completion of study treatment, patients followed up at day 1, 2, 3, 4, 8, 11, 14, 21, 28, 60, 90, 180, 270, 365, 545 and 730 and then periodically for up to 15 years.

Conditions

Interventions

TypeNameDescription
BIOLOGICALAutologous BAFFR-targeting CAR T CellsGiven IV
DRUGBendamustineGiven IV
PROCEDUREBiopsyUndergo biopsy
PROCEDUREBiospecimen CollectionUndergo blood sample collection
PROCEDUREBone Marrow Aspiration and BiopsyUndergo bone marrow biopsy/aspirate
PROCEDUREComputed TomographyUndergo CT scan
DRUGCyclophosphamideGiven IV
PROCEDUREEchocardiographyUndergo echocardiography
DRUGFludarabineGiven IV
PROCEDURELeukapheresisUndergo leukapheresis
PROCEDUREMagnetic Resonance ImagingUndergo MRI
PROCEDUREPositron Emission TomographyUndergo PET scan

Timeline

Start date
2024-03-18
Primary completion
2040-12-31
Completion
2040-12-31
First posted
2024-01-05
Last updated
2026-02-13

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT06191887. Inclusion in this directory is not an endorsement.