- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03624036
Study to Evaluate the Safety and Tolerability of Brexucabtagene Autoleucel (KTE-X19) in People With Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (ZUMA-8)
A Phase 1 Multicenter Study Evaluating the Safety and Tolerability of KTE-X19 in Adult Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma
The primary objective of this study is to evaluate the safety and tolerability of brexucabtagene autoleucel (KTE-X19) in adults with relapsed/refractory chronic lymphocytic leukemia (r/r CLL) and small lymphocytic lymphoma (r/r SLL) who have received at least 2 prior lines of treatment, one of which must include a Bruton's tyrosine kinase (BTK) inhibitor.
After the end of KTE-C19-108, participants who received an infusion of brexucabtagene autoleucel will complete the remainder of the 15-year follow-up assessments in a separate Long-term Follow-up study, KT-US-982-5968 (NCT05041309).
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Milano, Italy, 20132
- IRCCS Ospedale San Raffaele
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Arizona
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Phoenix, Arizona, United States, 85054
- Mayo Clinic - Arizona
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California
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Los Angeles, California, United States, 90095
- University of California Los Angeles (UCLA)
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Stanford, California, United States, 94035
- Stanford University
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Colorado
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Denver, Colorado, United States, 80218
- Sarah Cannon - Denver
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Florida
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Tampa, Florida, United States, 33612
- Moffitt Cancer Center
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Georgia
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Atlanta, Georgia, United States, 30322
- Emory University
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Kansas
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Westwood, Kansas, United States, 66205
- University of Kansas Cancer Center
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Dana Farber Cancer Institute
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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New Jersey
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Hackensack, New Jersey, United States, 07601
- Hackensack University Medical Center
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New York
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New York, New York, United States, 10021
- Memorial Sloan-Kettering
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Rochester, New York, United States, 14642
- University of Rochester
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Ohio
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Cleveland, Ohio, United States, 44195
- Cleveland Clinic - Taussig Cancer Institute
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Columbus, Ohio, United States, 43210
- Ohio State University
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19111
- Fox Chase Cancer Center
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Tennessee
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Nashville, Tennessee, United States, 37232
- Vanderbilt University
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Nashville, Tennessee, United States, 37203
- Sarah Cannon Research Center
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Texas
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Dallas, Texas, United States, 75246
- Baylor Cancer Hospital
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Houston, Texas, United States, 77030
- MD Anderson Cancer Center
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Washington
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Seattle, Washington, United States, 98104
- Swedish Cancer Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Key Inclusion Criteria:
Documentation of relapsed or refractory CLL and SLL; must have received at least 2 prior lines of treatment, one of which must include a Bruton's tyrosine kinase (BTK) inhibitor.
- Cohort 1 and 2: Participants with r/r CLL who have received at least 2 prior lines of treatment, one of which must include a BTK inhibitor.
- Cohort 3: Participants with r/r CLL and SLL must present with ≤ 1% circulating tumor cells in peripheral blood or absolute lymphocyte count (ALC) < 5000 cells/μL. Participants must have received at least 2 prior lines of treatment, one of which must include a BTK inhibitor.
- Cohort 4: Participants with r/r CLL who have received at least 2 prior lines of treatment and must have received ibrutinib as a single agent or in comibation with anti-cluster of differentiate 20 (CD20) antibodies, B-cell lymphoma 2 (BCL-2) inhibitors, and phosphoinositide 3-kinase inhibitor (PI3k) inhibitors for at least 6 months as the last line of therapy prior to screening. Ibrutinib administration will continue up to 30 hours prior to leukapheresis. In case of treatment interruption with ibrutinib, the principal investigator should reach out to the medical monitor to discuss.
- An indication for treatment per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria and radiographically measurable disease (at least 1 lesion > 1.5 cm in diameter)
Adequate hematologic function as indicated by:
- Platelet count ≥ 50 × 10^9/L
- Neutrophil count ≥ 0.5 × 10^9/L
- Hemoglobin ≥ 8 g/dL unless lower values are attributable to CLL
Adequate renal, hepatic, cardiac and pulmonary function defined as:
- Creatinine clearance (as estimated by Cockcroft-Gault) ≥ 60 mL/min
- Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 mg/dL unless participant has Gilbert's syndrome
- Left ventricular ejection fraction (LVEF) ≥ 50%, no evidence of pericardial effusion, no New York Heart Association (NYHA) class III or IV functional classification, no clinically significant arrhythmias
- No clinically significant pleural effusion
- Baseline oxygen saturation > 92% on room air
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy or BTKi (ibrutinib or acalabrutinib) at the time the participant is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy. At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy at the time the participant is planned for leukapheresis (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists)
Key Exclusion Criteria:
A history of treatment including any of the following:
- Prior cluster of differentiate 19 (CD19) directed therapy
- Prior allogeneic hematopoietic stem cell transplant (SCT) or donor lymphocyte infusion (DLI) within 6 months prior to enrollment
- History of autoimmune disease resulting in end-organ injury unless attributable to CLL (eg, idiopathic thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA))
- Diagnosis of Richter's transformation or a history of malignancy other than non-melanoma skin cancer or carcinoma in situ (eg, skin, cervix, bladder, breast), superficial bladder cancer, asymptomatic localized low grade prostate cancer for which watch-and-wait approach is standard of care, or any other cancer that has been in remission for > 3 years prior to enrollment
- History of severe hypersensitivity reaction attributed to aminoglycosides
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: First Stage Cohort 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg
Participants with relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL) will receive conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10^6 anti-cluster of differentiate 19 (CD19) chimeric antigen receptor (CAR) T cells/kg on Day 0.
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Administered intravenously
Administered intravenously
CAR-transduced autologous T cells administered intravenously
Other Names:
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Experimental: First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kg
Participants with r/r CLL will receive conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 2 x 10^6 anti-CD19 CAR T cells/kg on Day 0.
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Administered intravenously
Administered intravenously
CAR-transduced autologous T cells administered intravenously
Other Names:
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Experimental: Second Stage Cohort 3: 1 x 10^6 Anti-CD19 CAR T Cells/kg
Participants with r/r CLL and small lymphocytic lymphoma (SLL) with ≤1% malignant cells in peripheral blood or absolute lymphocyte count (ALC) < 5,000 cells/μL will receive conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10^6 anti-CD19 CAR T cells/kg on Day 0.
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Administered intravenously
Administered intravenously
CAR-transduced autologous T cells administered intravenously
Other Names:
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Experimental: Second Stage Cohort 4A: 1 x 10^6 Anti-CD19 CAR T Cells/kg
Participants with r/r CLL who previously received two lines of therapy along with ibrutinib with or without anti CD20 antibodies, B-cell lymphoma 2 (BCL-2) and Phosphoinositide 3-kinase (PI3k) inhibitors will receive ibrutinib up to 30 hours prior to leukapheresis along with conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10^6 anti-CD19 CAR T cells/kg on Day 0.
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Administered intravenously
Administered intravenously
CAR-transduced autologous T cells administered intravenously
Other Names:
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Experimental: Second Stage Cohort 4B: 2 x 10^6 Anti-CD19 CAR T Cells/kg
Participants with r/r CLL who previously received two lines of therapy along with ibrutinib with or without anti CD20 antibodies, BCL-2 and PI3k inhibitors will receive ibrutinib up to 30 hours prior to leukapheresis along with conditioning chemotherapy (fludarabine 30 mg/m^2/day over 30 minutes and cyclophosphamide 500 mg/m^2/day over 30-60 minutes) on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 2 x 10^6 anti-CD19 CAR T cells/kg on Day 0. Upon completion of Cohort 4A, it was determined not to enroll participants in Cohort 4B. |
Administered intravenously
Administered intravenously
CAR-transduced autologous T cells administered intravenously
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Experiencing Dose Limiting Toxicities (DLTs)
Time Frame: First infusion date of brexucabtagene autoleucel up to 28 days. Participants were evaluated in specified period but Grade 4 hematologic toxicity (specified in description) having onset in this period were further observed for 30 days for confirmation.
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DLTs refer to toxicities with onset experienced during the first 28 days of study treatment that have been judged to be clinically significant and related to study treatment.
DLTs evaluated may include with some exceptions: All brexucabtagene autoleucel related Grade 3 non-hematologic toxicities lasting for more than 7 days, Grade 4 non-hematologic toxicities regardless of duration, and Grade 4 hematologic toxicity lasting more than 30 days if not attributable to underlying disease.
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First infusion date of brexucabtagene autoleucel up to 28 days. Participants were evaluated in specified period but Grade 4 hematologic toxicity (specified in description) having onset in this period were further observed for 30 days for confirmation.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR) Per Investigator Review Assessed by International Workshop on CLL (IWCLL) 2018 Criteria
Time Frame: First infusion date up to last follow up visit (maximum duration: 42 months)
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ORR was defined as percentage of participants achieving either complete response (CR), complete response with incomplete hematopoetic recovery (CRi) or partial response (PR).
Criteria for CR: no lymphadenopathy >1.5 cm or hepatomegaly/splenomegaly, lymphocytes <4000/microliters (μL), bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules, platelets ≥100,000/µL, hemoglobin ≥11 grams per deciliter (g/dL).
CRi: All CR criteria were met except with platelet count <100,000/μL, hemoglobin <11 g/dL or neutrophil count <500/μL.
PR: ≥1 of these: ≥50% decrease in lymphocytes, lymphadenopathy, size of liver and spleen, 50% decrease in bone marrow infiltrates; and ≥1 of these: platelets ≥100,000/µL or ≥50% increase from Baseline, hemoglobin ≥11 g/dL or ≥50% increase from Baseline.
Participants who did not meet criteria were considered nonresponders.
95% confidence interval (CI) was calculated by Clopper-Pearson method.
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First infusion date up to last follow up visit (maximum duration: 42 months)
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Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)
Time Frame: First infusion date up to last follow up visit (maximum duration: 42 months)
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An AE is defined as any untoward medical occurrence in a clinical trial participant that does not necessarily have a relationship with study treatment or worsening of a pre-existing medical condition.
TEAEs were defined as AEs with onset on or after the initiation of brexucabtagene autoleucel infusion.
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First infusion date up to last follow up visit (maximum duration: 42 months)
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Peak Level of Anti-CD19 CAR T-Cells in Blood
Time Frame: First infusion date up to 3 months post-infusion (approximately 3 months)
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Peak was defined as the maximum number of CAR T cells measured post-infusion.
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First infusion date up to 3 months post-infusion (approximately 3 months)
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Kite Study Director, Kite, A Gilead Company
Publications and helpful links
General Publications
- Davids MS, Kenderian SS, Flinn IW, Hill BT, Maris M, Ghia P, et al. ZUMA-8: A Phase 1 Study of KTE-X19, an Anti-CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy, in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia. Blood. 2022;140:7454-6.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Leukemia, B-Cell
- Chronic Disease
- Lymphoma
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Immunological
- Cyclophosphamide
- Fludarabine
- Brexucabtagene autoleucel
Other Study ID Numbers
- KTE-C19-108
- 2018-001923-38 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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