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

NCT03624036 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: KTE-C19-1082018-001923-38
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 22

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing Dose Limiting Toxicities (DLTs)

  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.

  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.

Secondary Outcomes (3)

• Objective Response Rate (ORR) Per Investigator Review Assessed by International Workshop on CLL (IWCLL) 2018 Criteria

  First infusion date up to last follow up visit (maximum duration: 42 months)

• Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)

  First infusion date up to last follow up visit (maximum duration: 42 months)

• Peak Level of Anti-CD19 CAR T-Cells in Blood

  First infusion date up to 3 months post-infusion (approximately 3 months)

Study Arms (5)

First Stage Cohort 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg

EXPERIMENTAL

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.

Biological: brexucabtagene autoleucel; Drug: Fludarabine; Drug: Cyclophosphamide

First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kg

EXPERIMENTAL

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.

Biological: brexucabtagene autoleucel; Drug: Fludarabine; Drug: Cyclophosphamide

Second Stage Cohort 3: 1 x 10^6 Anti-CD19 CAR T Cells/kg

EXPERIMENTAL

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.

Biological: brexucabtagene autoleucel; Drug: Fludarabine; Drug: Cyclophosphamide

Second Stage Cohort 4A: 1 x 10^6 Anti-CD19 CAR T Cells/kg

EXPERIMENTAL

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.

Biological: brexucabtagene autoleucel; Drug: Fludarabine; Drug: Cyclophosphamide

Second Stage Cohort 4B: 2 x 10^6 Anti-CD19 CAR T Cells/kg

EXPERIMENTAL

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.

Biological: brexucabtagene autoleucel; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

brexucabtagene autoleucel BIOLOGICAL

CAR-transduced autologous T cells administered intravenously

Also known as: KTE-X19

First Stage Cohort 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg; First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kg; Second Stage Cohort 3: 1 x 10^6 Anti-CD19 CAR T Cells/kg; Second Stage Cohort 4A: 1 x 10^6 Anti-CD19 CAR T Cells/kg; Second Stage Cohort 4B: 2 x 10^6 Anti-CD19 CAR T Cells/kg

Fludarabine DRUG

Administered intravenously

First Stage Cohort 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg; First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kg; Second Stage Cohort 3: 1 x 10^6 Anti-CD19 CAR T Cells/kg; Second Stage Cohort 4A: 1 x 10^6 Anti-CD19 CAR T Cells/kg; Second Stage Cohort 4B: 2 x 10^6 Anti-CD19 CAR T Cells/kg

Cyclophosphamide DRUG

Administered intravenously

First Stage Cohort 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg; First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kg; Second Stage Cohort 3: 1 x 10^6 Anti-CD19 CAR T Cells/kg; Second Stage Cohort 4A: 1 x 10^6 Anti-CD19 CAR T Cells/kg; Second Stage Cohort 4B: 2 x 10^6 Anti-CD19 CAR T Cells/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kite, A Gilead Company: lead

Study Sites (22)

Mayo Clinic - Arizona

Phoenix, Arizona, 85054, United States

Location

University of California Los Angeles (UCLA)

Los Angeles, California, 90095, United States

Location

Stanford University

Stanford, California, 94035, United States

Location

Sarah Cannon - Denver

Denver, Colorado, 80218, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan-Kettering

New York, New York, 10021, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Cleveland Clinic - Taussig Cancer Institute

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Sarah Cannon Research Center

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Baylor Cancer Hospital

Dallas, Texas, 75246, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

Related Publications (2)

• 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.

  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.

  PMID: 40209059 DERIVED

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Recurrence; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

brexucabtagene autoleucel; fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Medical Information
• Organization: Kite, A Gilead Company

medinfo@kitepharma.com

844-454-5483 (1-844-454-KITE)

Study Officials

• Kite Study Director

  Kite, A Gilead Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2018
• First Posted: August 9, 2018
• Study Start: November 15, 2018
• Primary Completion: February 12, 2021
• Study Completion: November 18, 2022
• Last Updated: November 18, 2023
• Results First Posted: May 10, 2022

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (21); IT (1)