Study of Brexucabtagene Autoleucel in Adults With Rare B-cell Malignancies

• Status: Not yet recruiting
• Trial end date: 2029-11-01
• Target enrollment: 0
• Participant gender: All

Summary

Master protocol: The primary objective of this study is to evaluate the efficacy of brexucabtagene autoleucel in four rare B-cell malignancies. This study will use a basket study design with separate, indication-specific substudies, to investigate relapsed/refractory Waldenstrom macroglobulinemia (r/r WM), relapsed/refractory Richter transformation (r/r RT), relapsed/refractory Burkitt lymphoma (r/r BL), and relapsed/refractory hairy cell leukemia (r/r HCL).

Substudy A: The primary objective of this substudy is to evaluate the efficacy of brexucabtagene autoleucel in participants with r/r WM by determining the combined rate of complete response (CR) and very good partial response (VGPR) by central assessment.

Substudy B: The primary objective of this substudy is to evaluate the efficacy of brexucabtagene autoleucel on diffuse large B-cell lymphoma-Richter transformation (DLBCL-RT) in participants with r/r RT, by determining the objective response rate (ORR) by central assessment.

Substudy C: The primary objective of this substudy is to evaluate the efficacy of brexucabtagene autoleucel in participants with r/r BL, by determining the ORR by central assessment.

Substudy D: The primary objective of this substudy is to evaluate the efficacy of brexucabtagene autoleucel in participants with r/r HCL by determining the ORR by central assessment.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kite, A Gilead Company
• Treatments: Cyclophosphamide; Fludarabine

Criteria

Key Inclusion Criteria:

All Substudies:

• Presence of toxicities due to prior therapy must be stable and recovered to Grade 1 or lower.

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

• Adequate hematologic and end-organ function.

• Individuals of childbearing potential who engage in heterosexual intercourse must agree to use specified method(s) of contraception.

Substudy A:

• Confirmed clinicopathological diagnosis of Waldenstrom macroglobulinemia (WM) in accordance with the consensus panel of the Second International Workshop on WM.

• Relapsed or refractory disease after 2 or more lines of therapy.

• Prior therapy must have included a Bruton's tyrosine kinase (BTK) inhibitor. Also, chemotherapy and/or a proteasome inhibitor must have been attempted, with either subsequent documented disease progression or no response (stable disease).

• Requiring treatment as defined in the recommendations from the Second International Workshop on WM.

• Measurable disease, defined as presence of serum immunoglobulin (Ig)M with a minimum IgM level of > 2 times the upper limit of normal of each institution is required.

• The inclusion criteria concerning washout periods prior to leukapheresis in the master protocol must be met, with the exception that ibrutinib may be continued through leukapheresis and up to 5 half-lives (30 hours) prior to the start of lymphodepletion.

Substudy B:

• Confirmed diagnosis of chronic lymphocytic leukemia (CLL) based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria with histologically confirmed Richter transformation (RT) to a diffuse large B-cell lymphoma (DLBCL) subtype.

• Relapsed or refractory disease after 1 line of therapy, defined as at least 1 of the following:

• Refractory disease, defined as progressive disease or stable disease as best response to first-line therapy.

• Relapsed disease, defined as complete remission to first-line therapy followed by biopsy-proven disease relapse.

• At least 1 measurable lesion based on the Lugano Classification. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.

Substudy C:

• Histologically confirmed mature B-cell non-Hodgkin lymphoma (NHL) Burkitt lymphoma/leukemia.

• Relapsed or refractory disease after first-line chemoimmunotherapy, defined as 1 of the following:

• Refractory disease, defined as progressive disease or stable disease as best response to first-line therapy; individuals who are intolerant to first-line therapy are excluded.

• Relapsed disease, defined as complete remission to first-line therapy followed by biopsy-proven disease relapse.

• At least 1 measurable lesion based on the Lugano Classification. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.

Substudy D:

• Individuals must have histologically confirmed hairy cell leukemia (HCL) with a need for therapy based on at least one of the following criteria:

• neutrophils < 1.0 x 10^9/L

• platelets < 100 x 10^9/L

• hemoglobin < 11 g/dL

• symptomatic splenomegaly

• symptomatic lymphadenopathy

• Individuals must have received:

• At least 2 prior therapies, including at least a purine nucleoside analog (PNA) and moxetumomab pasudotox if eligible and available.

Key Exclusion Criteria:

All Substudies:

• Prior CAR therapy or treatment with any anti-CD19 therapy.

• HIV-positive patients, unless taking appropriate anti-HIV medications, having an undetectable viral load by quantitative polymerase chain reaction (qPCR) and a CD4 count > 200 cells/uL.

• History or presence of detectable cerebrospinal fluid malignant cells or brain metastases, with the exception of prior central nervous system (CNS) disease in WM.

• History of autoimmune disease (eg, Crohn's disease, rheumatoid arthritis, systemic lupus).

Substudy A:

• History of allogeneic stem cell transplantation. A prior autologous stem cell transplantation is allowed, but at least 6 months should have elapsed.

• Plasmapheresis for symptomatic hyperviscosity or serum IgM > 5,000 mg/dL < 35 days prior to the screening IgM assessment.

• Exclusion of IgM monoclonal gammopathy of undetermined significance or IgM multiple myeloma.

• Presence of CNS involvement (Bing-Neel syndrome). Individuals with a prior history of Bing-Neel syndrome are eligible if they show a negative cerebrospinal fluid (CSF) and no involvement by imaging.

Substudy B:

• Diagnosis of RT not of DLBCL subtype (including, but not limited to, Hodgkin lymphoma (HL) and prolymphocytic leukemia).

• Prior allogeneic or autologous stem cell transplant < 3 months prior to screening and/or < 4 months prior to planned infusion of brexucabtagene autoleucel.

• Presence of active graft-versus-host disease following prior stem cell transplant.

Substudy C:

• Burkitt-like lymphoma with 11q aberration, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement, or high-grade B-cell lymphoma not otherwise specified.

• Prior allogeneic stem cell transplant < 3 months prior to screening and/or < 4 months prior to planned infusion of brexucabtagene autoleucel.

• Presence of active graft-versus-host disease following prior allogeneic stem cell transplant.

Substudy D:

• Prior history of allogeneic stem cell transplant.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.