About this trial

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.

Eligibility criteria

Qualifiers

PRE-REGISTRATION: Age ≥ 18 years

PRE-REGISTRATION: Confirmed diagnosis of 1 of the following relapsed or refractory B-cell hematologic malignancies: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), or large B cell lymphoma (LBCL) including Richter's transformation from CLL/SLL

Demonstration of progressive or stable disease by positron emission tomography/computed tomography (PET/CT) or computed tomography (CT) criteria according to the international workshop on chronic lymphocytic leukemia (iwCLL) 2018 criteria

Demonstration of progressive or stable disease by PET/CT or CT criteria as the best response to the most recent chemotherapy regimen according to the revised Lugano Response Criteria for Malignant Lymphoma

Disqualifiers

PRE-REGISTRATION: Prior solid organ transplantation

PRE-REGISTRATION: Unstable angina, clinically significant arrhythmia, or myocardial infarction ≤ 6 months of prior to pre-registration, or grade 3 or higher pericardial effusion at the time of pre-registration

PRE-REGISTRATION: Prior anti-BAFF-R therapies

PRE-REGISTRATION: Known contraindication to lymphodepleting (LD) chemotherapy

Trial design

Treatments tested in this trial

  • Autologous BAFFR-targeting CAR T Cells
  • Bendamustine
  • Biopsy
  • Biospecimen Collection
  • Bone Marrow Aspiration and Biopsy
  • Computed Tomography
  • Cyclophosphamide
  • Echocardiography
  • Fludarabine
  • Leukapheresis
  • Magnetic Resonance Imaging
  • Positron Emission Tomography

Treatment groups

27 Participants
are divided into 1 treatment group

Locations

1
Mayo Clinic in Florida32224-9980, JacksonvilleFlorida, United States

Sponsors and collaborators

Mayo Clinic

Lead sponsor