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

Recruiting now · Phase 1

Conditions studied: B-Cell Non-Hodgkin Lymphoma, Recurrent Chronic Lymphocytic Leukemia, Recurrent Diffuse Large B-Cell Lymphoma, Recurrent Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Small Lymphocytic Lymphoma, Recurrent Transformed Chronic Lymphocytic Leukemia, Refractory Chronic Lymphocytic Leukemia, Refractory Diffuse Large B-Cell Lymphoma, Refractory Follicular Lymphoma, Refractory Mantle Cell Lymphoma, Refractory Marginal Zone Lymphoma, Refractory Small Lymphocytic Lymphoma, Refractory Transformed Chronic Lymphocytic Leukemia

In brief

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.

Key facts

Study ID

NCT06191887

Run by

Mayo Clinic

People needed

27

Starts

2024-03-18

Expected to finish

2040-12-31

Last updated by the study team

2026-02-13

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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
• For CD19+ B cell malignancies; relapsed or refractory disease is defined by one of the following histopathology:
• Biopsy proven SLL or flow cytometry proven CLL; relapsed or refractory disease is defined as:
• 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
• Biopsy proven B-cell non-Hodgkin lymphoma (NHL) of any histopathology (including Richter Transformation of CLL); relapsed or refractory disease is defined as:
• 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
• PRE-REGISTRATION: Disease Specific prior lines of therapies below:
• For CLL/SLL, patients must have received ≥ two prior lines of therapy, and/or ≥ 6 months of second line prior BTK inhibition (e.g. ibrutinib or other such as acalabrutinib or zanubrutinib) and must have failed to respond to venetoclax or be intolerant. Exception: Patients in stable disease (SD) or partial response (PR) with a known ibrutinib resistance mutation (BTK or phospholipase Cγ2) may be included even if on ibrutinib therapy for less than 6 months
• These patients may or may not have received prior antibody directed against cluster of differentiation 20 (CD20).
• For Follicular Lymphoma, patients must have received ≥ two prior lines of therapy, including an antibody directed against CD20.
• NOTE: Prior cluster of differentiation 19 (CD19) directed chimeric antigen receptor T-cell therapy (CART) must have a 100-day washout period.
• For Mantle Cell Lymphoma, patients must have received ≥ two prior lines of therapy, including an antibody directed against CD20, and a BTK inhibitor.
• NOTE: Prior CD19 directed CART must have a 100-day washout period.
• For Marginal Zone Lymphoma, patients must have received ≥ two prior lines of therapy, including an antibody directed against CD20.
• NOTE: Prior CD19 directed CART must have a 100-day washout period.
• For Large B cell Lymphoma, patients must have received ≥ two prior lines of therapy, including an antibody directed against CD20. Prior exposure to CD19 directed CART will be allowed at the discretion of the Principal Investigator.
• NOTE: Prior failed CD19 directed CART must have a 100-day washout period
• For Richter's Transformation, patients must have received ≥two prior lines of therapy, including an antibody directed against CD20.
• 100-day washout period starts from the date of the last prior CAR-T infusion.
• PRE-REGISTRATION: Measurable disease
• REGISTRATION: Positive BAFFR test
• REGISTRATION: Measurable disease
• REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• REGISTRATION: Hemoglobin ≥ 9.0 g/dL (unless due to documented marrow involvement with disease) obtained ≤14 days prior to registration

You may not qualify if…

• 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
• PRE-REGISTRATION: Use of systemic antitumor therapy or investigational agent ≤ 14 days, prior to pre-registration
• PRE-REGISTRATION: Receiving any other investigational agent which would be considered as a treatment for the BAFF-R
• PRE-REGISTRATION: Autologous HCT ≤ 60 days prior to pre-registration
• PRE-REGISTRATION: Uncontrolled intercurrent non-cardiac illness including, but not limited to:
• Previous or concurrent malignancy
• Ongoing or active infection
• Psychiatric illness/social situations
• Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy * Persons of childbearing potential who are pregnant or breastfeeding
• Life Expectancy of < 6 weeks
• Persons requiring systemic corticosteroids (>10 mg prednisone or equivalent per day) and/or other immunosuppressive therapy. Patients are allowed to use topical corticosteroids
• Any other conditions that would limit compliance with study requirements
• PRE-REGISTRATION: Detectable malignant cells from cerebrospinal fluid (CSF) or magnetic resonance imaging (MRI) indicating brain metastases during screening, or a history of central nervous system (CNS) involvement by malignancy (CSF or imaging) with still active disease. Note: Patients with a history of CNS involvement resolving after treatment and without active disease will be considered eligible if other inclusion criteria are met
• PRE-REGISTRATION: History of a seizure disorder, major cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
• PRE-REGISTRATION: Radiation therapy ≤ 14 days prior to pre-registration
• PRE-REGISTRATION: Prior allogeneic hematopoietic stem cell transplant (HCT) in ≤ 6 months prior to pre-registration; patients with active graft versus host disease (GVHD) will not be eligible regardless of duration from prior allogeneic HCT
• PRE-REGISTRATION: Human immunodeficiency virus (HIV) positive patients
• PRE-REGISTRATION: Subjects with New York Health Association (NYHA) class III or greater heart failure
• REGISTRATION: Eligible for auto-HCT based on investigator judgement
• REGISTRATION: Presence of active bacterial, viral, or fungal infection that is uncontrolled, based on investigator judgment
• REGISTRATION: Patients with active hepatitis B or hepatitis C infections are excluded from the study. Patients who are documented to be HIV positive or proven HIV infection from testing are ineligible for the study. Infectious disease testing (HIV-1, HIV-2, hepatitis C virus (HCV) antibody and polymerase chain reaction (PCR), hepatitis B virus (HBV) surface antigen, HBV surface antibody, HBV core antibody) performed ≤ 45 days prior to registration may be considered for subject eligibility
• REGISTRATION: Previous or concurrent malignancy, except basal cell or squamous cell skin carcinoma, adequately resected and in situ carcinoma of cervix, or a previous malignancy that was completely resected and has been in remission for ≥ 5 years prior to registration

Where it is running

• Mayo Clinic in Florida — Jacksonville, Florida, United States (enrolling)

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.