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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Given IV
Given IV
Undergo biopsy
Undergo blood sample collection
Undergo bone marrow biopsy/aspirate
Undergo CT scan
Given IV
Undergo echocardiography
Given IV
Undergo leukapheresis
Undergo MRI
Undergo PET scan
Mayo Clinic in Florida
Jacksonville, Florida, United States
RECRUITINGIncidence of dose-limiting toxicities (DLT)
DLTs are defined per the protocol and assessed by the number of DLTs that occur during the DLT evaluation period and persist beyond the specified duration (relative to the time of onset, defined as within 28 days).
Time frame: Up to 28 days after MC10029 (autologous B-cell activating factor receptor [BAFFR]-targeting chimeric antigen receptor [CAR] T cells product) infusion
Incidence and severity of treatment emergent adverse events
Defined as adverse events (AEs) that occur or worsen in severity on or after MC10029 product infusion.
Time frame: Up to 15 years
Overall response rate
Will be estimated by the number of patients with an objective status of complete response (CR) or partial response (PR) by the positron emission tomography-computed tomography (PET-CT) based response criteria . Will be assessed according to Lugano criteria for lymphomas (follicular lymphoma \[FL\], mantle cell lymphoma \[MCL\], marginal zone lymphoma \[MZL\], large b-cell lymphoma \[LBCL\]) and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria for chronic lymphocytic leukemia (CLL).
Time frame: Up to 15 years
Complete response rate
Will be assessed according to Lugano criteria for lymphomas (FL, MCL, MZL, LBCL) and iwCLL 2018 criteria for CLL.
Time frame: Up to 15 years
Duration of response
Defined as the time from onset of response to progression or death due to any reason, whichever occurs earlier.
Time frame: Up to 15 years
Progression free survival
Defined as the time from initiation of treatment to the occurrence of disease progression or death.
Time frame: Up to 15 years
Overall survival
Defined as the time from treatment to death, regardless of disease recurrence.
Time frame: Up to 15 years
Number of conforming versus nonconforming products
Will be noted and reported. A conforming cell product product must have met all release criteria for infusion. No patient will receive a non-conforming product under this protocol, thus this endpoint will be evaluated by the Quality Assurance/Quality Control team.
Time frame: Up to 15 years
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