Health TrialsbyHealthPanel

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

ConditionsB-Cell Non-Hodgkin LymphomaRecurrent Chronic Lymphocytic LeukemiaRecurrent Diffuse Large B-Cell LymphomaRecurrent Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaRecurrent Small Lymphocytic LymphomaRecurrent Transformed Chronic Lymphocytic LeukemiaRefractory Chronic Lymphocytic LeukemiaRefractory Diffuse Large B-Cell LymphomaRefractory Follicular LymphomaRefractory Mantle Cell LymphomaRefractory Marginal Zone LymphomaRefractory Small Lymphocytic LymphomaRefractory Transformed Chronic Lymphocytic Leukemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorMayo Clinic

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

This trial does not accept healthy volunteers

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

Design model

Single group

Treatments tested in this trial

  • Autologous BAFFR-targeting CAR T Cells

    Biological/Vaccine

    Given IV

  • Bendamustine

    Drug

    Given IV

  • Biopsy

    Procedure/Surgery

    Undergo biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Bone Marrow Aspiration and Biopsy

    Procedure/Surgery

    Undergo bone marrow biopsy/aspirate

  • Computed Tomography

    Procedure/Surgery

    Undergo CT scan

  • Cyclophosphamide

    Drug

    Given IV

  • Echocardiography

    Procedure/Surgery

    Undergo echocardiography

  • Fludarabine

    Drug

    Given IV

  • Leukapheresis

    Procedure/Surgery

    Undergo leukapheresis

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Positron Emission Tomography

    Procedure/Surgery

    Undergo PET scan

Treatment groups

27 Participants
are divided into 1 treatment group
Group A: Treatment (BARRF based chimeric antigen receptor T-cells)Experimental treatment 12 interventions

Trial outcomes

Primary outcomes

1

Incidence 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
2

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

Secondary outcomes

1

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
2

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
3

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
4

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Mayo Clinic

Lead sponsor

Source ClinicalTrials.gov
Apply now