Chronic Lymphocytic Leukemia Clinical Trial

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

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.

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Full Description

After completing the treatment period, all participants will be followed in the post-treatment follow-up period. Thereafter, participants will transition to a separate long-term follow-up study (KT-US-982-5968) to continue follow-up out to 15 years.

View Eligibility Criteria

Eligibility 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.

Study is for people with:

Chronic Lymphocytic Leukemia

Phase:

Phase 2

Estimated Enrollment:

170

Study ID:

NCT05537766

Recruitment Status:

Recruiting

Sponsor:

Kite, A Gilead Company

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There are 2 Locations for this study

See Locations Near You

Colorado Blood Cancer Institute
Denver Colorado, 80218, United States
Tennessee Oncology, PLLC
Nashville Tennessee, 37203, United States

How clear is this clinincal trial information?

Study is for people with:

Chronic Lymphocytic Leukemia

Phase:

Phase 2

Estimated Enrollment:

170

Study ID:

NCT05537766

Recruitment Status:

Recruiting

Sponsor:


Kite, A Gilead Company

How clear is this clinincal trial information?

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