Study to Evaluate the Safety and Tolerability of Brexucabtagene Autoleucel (KTE-X19) in People With Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

NCT ID: NCT03624036

Last Updated: 2023-11-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-15
• Study Completion Date: 2022-11-18

Brief Summary

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).

Conditions

Relapsed/Refractory Chronic Lymphocytic Leukemia and Relapsed/Refractory Small Lymphocytic Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

brexucabtagene autoleucel

Intervention Type: BIOLOGICAL

CAR-transduced autologous T cells administered intravenously

Fludarabine

Intervention Type: DRUG

Administered intravenously

Cyclophosphamide

Intervention Type: DRUG

Administered intravenously

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.

Group Type: EXPERIMENTAL

brexucabtagene autoleucel

Intervention Type: BIOLOGICAL

CAR-transduced autologous T cells administered intravenously

Fludarabine

Intervention Type: DRUG

Administered intravenously

Cyclophosphamide

Intervention Type: DRUG

Administered intravenously

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.

Group Type: EXPERIMENTAL

brexucabtagene autoleucel

Intervention Type: BIOLOGICAL

CAR-transduced autologous T cells administered intravenously

Fludarabine

Intervention Type: DRUG

Administered intravenously

Cyclophosphamide

Intervention Type: DRUG

Administered intravenously

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.

Group Type: EXPERIMENTAL

brexucabtagene autoleucel

Intervention Type: BIOLOGICAL

CAR-transduced autologous T cells administered intravenously

Fludarabine

Intervention Type: DRUG

Administered intravenously

Cyclophosphamide

Intervention Type: DRUG

Administered intravenously

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.

Group Type: EXPERIMENTAL

brexucabtagene autoleucel

Intervention Type: BIOLOGICAL

CAR-transduced autologous T cells administered intravenously

Fludarabine

Intervention Type: DRUG

Administered intravenously

Cyclophosphamide

Intervention Type: DRUG

Administered intravenously

Interventions

brexucabtagene autoleucel

CAR-transduced autologous T cells administered intravenously

Intervention Type: BIOLOGICAL

Fludarabine

Administered intravenously

Intervention Type: DRUG

Cyclophosphamide

Administered intravenously

Intervention Type: DRUG

Other Intervention Names

KTE-X19

Eligibility Criteria

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)

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kite, A Gilead Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kite Study Director

Role: STUDY_DIRECTOR

Kite, A Gilead Company

Locations

Mayo Clinic - Arizona

Phoenix, Arizona, United States

University of California Los Angeles (UCLA)

Los Angeles, California, United States

Stanford University

Stanford, California, United States

Sarah Cannon - Denver

Denver, Colorado, United States

Moffitt Cancer Center

Tampa, Florida, United States

Emory University

Atlanta, Georgia, United States

University of Kansas Cancer Center

Westwood, Kansas, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Memorial Sloan-Kettering

New York, New York, United States

University of Rochester

Rochester, New York, United States

Cleveland Clinic - Taussig Cancer Institute

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Sarah Cannon Research Center

Nashville, Tennessee, United States

Vanderbilt University

Nashville, Tennessee, United States

Baylor Cancer Hospital

Dallas, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

Swedish Cancer Institute

Seattle, Washington, United States

IRCCS Ospedale San Raffaele

Milan, , Italy

Countries

United States; Italy

References

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.

Reference Type: RESULT

Davids MS, Kenderian SS, Flinn I, Hill BT, Maris M, Ghia P, Byrne M, Bartlett NL, Pagel JM, Zheng Y, Kanska J, Zhang W, Granados E, Pinilla-Ibarz J. ZUMA-8: a phase 1 study of brexucabtagene autoleucel in patients with relapsed/refractory chronic lymphocytic leukemia. Blood. 2025 Aug 21;146(8):938-943. doi: 10.1182/blood.2024027460.

Reference Type: DERIVED

PMID: 40209059 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan: Statistical Analysis Plan

View Document

Document Type: Statistical Analysis Plan: Translational Statistical Analysis Plan

View Document

Related Links

https://www.gileadclinicaltrials.com/study/?id=KTE-C19-108

Gilead Clinical Trials Website

Other Identifiers

2018-001923-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KTE-C19-108

Identifier Type: -

Identifier Source: org_study_id