Trial Title:
Study of Brexucabtagene Autoleucel in Adults With Rare B-cell Malignancies
NCT ID:
NCT05537766
Condition:
Relapsed/Refractory Waldenstrom Macroglobulinemia
Relapsed/Refractory Richter Transformation
Relapsed/Refractory Burkitt Lymphoma
Relapsed/Refractory Hairy Cell Leukemia
Conditions: Official terms:
Burkitt Lymphoma
Waldenstrom Macroglobulinemia
Leukemia, Hairy Cell
Cyclophosphamide
Fludarabine
Brexucabtagene autoleucel
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Brexucabtagene Autoleucel
Description:
Administered intravenously
Arm group label:
Substudy A (Relapsed/Refractory Waldenstrom Macroglobulinemia): Brexucabtagene Autoleucel
Arm group label:
Substudy B (Relapsed/Refractory Richter Transformation): Brexucabtagene Autoleucel
Arm group label:
Substudy C (Relapsed/Refractory Burkitt Lymphoma): Brexucabtagene Autoleucel
Arm group label:
Substudy D (Relapsed/Refractory hairy cell leukemia): Brexucabtagene Autoleucel
Other name:
KTE-X19
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Administered intravenously
Arm group label:
Substudy A (Relapsed/Refractory Waldenstrom Macroglobulinemia): Brexucabtagene Autoleucel
Arm group label:
Substudy B (Relapsed/Refractory Richter Transformation): Brexucabtagene Autoleucel
Arm group label:
Substudy C (Relapsed/Refractory Burkitt Lymphoma): Brexucabtagene Autoleucel
Arm group label:
Substudy D (Relapsed/Refractory hairy cell leukemia): Brexucabtagene Autoleucel
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
Administered intravenously
Arm group label:
Substudy A (Relapsed/Refractory Waldenstrom Macroglobulinemia): Brexucabtagene Autoleucel
Arm group label:
Substudy B (Relapsed/Refractory Richter Transformation): Brexucabtagene Autoleucel
Arm group label:
Substudy C (Relapsed/Refractory Burkitt Lymphoma): Brexucabtagene Autoleucel
Arm group label:
Substudy D (Relapsed/Refractory hairy cell leukemia): Brexucabtagene Autoleucel
Summary:
Master protocol: The goal of this master clinical study is to test how well the study
drug, brexucabtagene autoleucel, works in participants with rare B-cell malignancies:
relapsed/refractory Waldenstrom macroglobulinemia (r/r WM) (Substudy A - no longer
recruiting), relapsed/refractory Richter transformation (r/r RT) (Substudy B),
relapsed/refractory Burkitt lymphoma (r/r BL) (Substudy C and relapsed/refractory hairy
cell leukemia (r/r HCL) (Substudy D - no longer recruiting).
Detailed description:
Master protocol: The primary objective of this study is to evaluate the efficacy of
brexucabtagene autoleucel in two rare B-cell malignancies. This study will use a basket
study design with separate, indication-specific substudies, to investigate r/r RT and r/r
BL.
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.
Substudies A and D have been early terminated by the sponsor.
Criteria for 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 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.
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.
- Presence of detectable cerebrospinal fluid malignant cells or brain metastases.
- History of autoimmune disease (eg, Crohn's disease, rheumatoid arthritis, systemic
lupus).
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.
- Presence of CNS involvement. Individuals with a prior history of CNS involvement are
eligible if they show a negative CSF and no involvement by imaging.
Substudies A and D have been early terminated by the sponsor.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope (City of Hope National Medical Center)
Address:
City:
Duarte
Zip:
91010
Country:
United States
Facility:
Name:
Stanford Cancer Institute
Address:
City:
Stanford
Zip:
94305
Country:
United States
Facility:
Name:
Colorado Blood Cancer Institute
Address:
City:
Denver
Zip:
80218
Country:
United States
Facility:
Name:
Georgetown University Medical Centre
Address:
City:
Washington
Zip:
20037
Country:
United States
Facility:
Name:
University of Iowa
Address:
City:
Iowa City
Zip:
52242
Country:
United States
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Facility:
Name:
Hackensack University Medical Center
Address:
City:
Hackensack
Zip:
07601
Country:
United States
Facility:
Name:
The Ohio State University Wexner Medical Center - James Cancer HospitalS
Address:
City:
Columbus
Zip:
43210
Country:
United States
Facility:
Name:
UPMC Hillman Cancer Center
Address:
City:
Pittsburgh
Zip:
15232
Country:
United States
Facility:
Name:
Tennessee Oncology, PLLC
Address:
City:
Nashville
Zip:
37203
Country:
United States
Facility:
Name:
Vanderbilt University
Address:
City:
Nashville
Zip:
37232
Country:
United States
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Facility:
Name:
Medical University of Vienna, Department of Internal Medicine I, Div. of Hematology
Address:
City:
Vienna
Zip:
01090
Country:
Austria
Facility:
Name:
Hopital de la Pitie Salpetriere
Address:
City:
Paris
Zip:
75013
Country:
France
Facility:
Name:
Centre hospitalier de Toulouse - Hematology department
Address:
City:
Toulouse Cedex 09
Zip:
31059
Country:
France
Facility:
Name:
Universitatsklinikum Heidelberg
Address:
City:
Heidelberg
Zip:
69120
Country:
Germany
Facility:
Name:
Universitatsklinikum Koln
Address:
City:
Koln
Zip:
50937
Country:
Germany
Facility:
Name:
Universitatsklinikum Ulm
Address:
City:
Ulm
Zip:
89081
Country:
Germany
Facility:
Name:
IRCCS Azienda Ospedaliero - Universitaria di Bologna
Address:
City:
Bologna
Zip:
40138
Country:
Italy
Facility:
Name:
ASST Grande Ospedale Metropolitano Niguarda
Address:
City:
Milano
Zip:
20162
Country:
Italy
Facility:
Name:
Azienda Ospedale di Perugia - Ospedale S. Maria della Misericordia
Address:
City:
Perugia
Zip:
06132
Country:
Italy
Facility:
Name:
Radboud University Nijmegen Medical Centre
Address:
City:
Nijmegen
Zip:
6525 GA
Country:
Netherlands
Facility:
Name:
Hospital Clinic de Barcelona
Address:
City:
Barcelona
Zip:
08036
Country:
Spain
Facility:
Name:
Hospital Universitario de Salamanca
Address:
City:
Salamanca
Zip:
37007
Country:
Spain
Facility:
Name:
Hospital Universitario Virgen del Rocio
Address:
City:
Sevilla
Zip:
41013
Country:
Spain
Facility:
Name:
Istituto Oncologico Della Svizzera Italiana (IOSI)
Address:
City:
Bellinzona
Zip:
6500
Country:
Switzerland
Start date:
November 1, 2022
Completion date:
March 2025
Lead sponsor:
Agency:
Kite, A Gilead Company
Agency class:
Industry
Source:
Gilead Sciences
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05537766
https://www.gileadclinicaltrials.com/study/?id=KT-US-568-0138
