This phase I trial tests the safety and side effects of B-cell activating factor receptor (BAFFR) chimeric antigen receptor (CAR) T cells and how well they work in treating patients with B-cell acute lymphoblastic leukemia (B-ALL) and B-cell lymphoblastic lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). CAR T-cell therapy, such as BAFFR-CAR 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 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 BAFFR-CAR T cells may be safe, tolerable and/or effective in treating patients with relapsed or refractory B-cell ALL and B-cell lymphoblastic lymphoma.
PRIMARY OBJECTIVE: I. Assess the safety of administering autologous BAFFR-targeting CAR T cells (BAFFR\[EQ\]BBζ/EGFRt T cells) (also known as \[aka\], BAFFR-CAR T cells). SECONDARY OBJECTIVES: I. Evaluate the ability of BAFFR-CAR T cells to mediate clinical response in participants with B-ALL. II. Evaluate the level of residual disease in participants who achieve remission after BAFFR-CAR T cell treatment. III. Evaluate the duration of B cell aplasia as a surrogate for BAFFR-CAR T cell activity. IV. Evaluate the rate and severity of graft-versus-host disease (GVHD) in recipients of prior allogeneic hematopoietic stem cell transplantation (allogeneic hematopoietic stem cell transplantation \[allo-HCT\]). V. Evaluate progression-free survival (PFS) and overall survival (OS). EXPLORATORY OBJECTIVES: I. Measure expansion and persistence of BAFFR-CAR T cells in the peripheral blood (PB), bone marrow (BM), and cerebrospinal fluid (CSF), when available, and explore the correlation with BAFFR-CAR T cell efficacy. II. Measure BAFF-R expression on leukemic cells, as well as other disease markers, before and after BAFFR-CAR T cell treatment and explore association with response and relapse, when feasible. III. Measure cytokine levels in PB and CSF, when available, and explore association with response. OUTLINE: Patients undergo leukapheresis and may receive bridging therapy per treating physician discretion. Patients then receive lymphodepletion therapy with cyclophosphamide intravenously (IV) and fludarabine IV on days -5 to -3 and BAFFR-CAR T cells IV over 10-15 minutes on day 0. Patients also undergo blood sample collection, bone marrow aspiration and biopsy, chest x-ray, and positron emission tomography (PET)/computed tomography (CT) or CT throughout the study. Additionally, patients may also undergo liver ultrasonographic elastography at screening at discretion of investigator and brain magnetic resonance imaging (MRI) or CT, CSF specimen collection, and echocardiography (ECHO) or multigated acquisition scan (MUGA) throughout the study After completion of study treatment, patients are followed up within 18-24 hours, at least every 2 days for 14 days, at 14, 21, 28, 60, and 100 days, at 4, 6, 7, and 12 months, then yearly for up to a total of 15 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Given IV
Undergo blood and CSF specimen collection
Undergo bone marrow aspiration and biopsy
Undergo bone marrow aspiration and biopsy
Receive bridging therapy
Undergo chest x-ray
Undergo CT or PET/CT
Given IV
Undergo ECHO
Given IV
Undergo leukapheresis
Undergo brain MRI
Undergo MUGA
Undergo PET/CT
Undergo liver ultrasonographic elastography
City of Hope Medical Center
Duarte, California, United States
City of Hope at Irvine Lennar
Irvine, California, United States
Incidence of adverse events
Will be graded using Common Terminology Criteria for Adverse Events version 5.0, American Society for Transplantation and Cellular Therapy Consensus Criteria on Cytokine Release Syndrome/Neurotoxicity, graft-versus-host disease (GVHD) criteria, and Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome identification and grading. Will be summarized by organ involved, severity, time of onset, and attribution.
Time frame: Up to 28 days after chimeric antigen receptor (CAR) T cells
Dose-limiting toxicity
Will be described individually.
Time frame: From the start of CAR T infusion up to 28 days
Disease response rate
Will be defined as complete response (CR) or CR with incomplete blood count recovery or CR with partial hematological recovery. Will be evaluated using European LeukemiaNet criteria. Rates and associated 95% binomial exact confidence limits will be estimated.
Time frame: At 4 weeks
Minimal residual disease negative rate
Will be defined by malignant cells \< 0.01% by flow cytometry or clonoSEQ. Rates and associated 95% binomial exact confidence limits will be estimated.
Time frame: At 4 weeks
Duration of B-cell aplasia
Will be measured by serum immunoglobulin G level. Will be summarized by descriptive statistics.
Time frame: Up to 15 years
Severity of GVHD in recipients of prior allogeneic hematopoietic stem cell transplantation
Will be defined per Keystone criteria for acute GVHD and revised National Institutes of Health consensus on grading of chronic GVHD. Competing risk method will be used to estimate.
Time frame: Within 8 weeks after T cell infusion
Progression-free survival
Kaplan-Meier product limit method with log-log transformation for the confidence interval will be used to estimate.
Time frame: From T cell infusion to the first observation of disease relapse/progression or death from any cause, whichever occurs first, assessed up to 15 years
Overall survival
Kaplan-Meier product limit method with log-log transformation for the confidence interval will be used to estimate.
Time frame: From T cell infusion to death from any cause, assessed up to 15 years
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