Clinical trial · Interventional
Study to Evaluate the Safety and Tolerability of Brexucabtagene Autoleucel (KTE-X19) in People With Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): Development program terminated
Summary
Brief summary (as posted)
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
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Relapsed/Refractory Chronic Lymphocytic Leukemia and Relapsed/Refractory Small Lymphocytic Lymphoma | — | UNRESOLVED | — |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| brexucabtagene autoleucel | Biological | Brexucabtagene Autoleucel | ALIAS |
| Cyclophosphamide | Drug | Cyclophosphamide | ALIAS |
| Fludarabine | Drug | Fludarabine | ALIAS |
Design
Arms and outcomes
Arms (5)
- type
- EXPERIMENTAL
- label
- First Stage Cohort 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg
- description
- 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.
- interventionNames
- Biological: brexucabtagene autoleucel
- Drug: Fludarabine
- Drug: Cyclophosphamide
- type
- EXPERIMENTAL
- label
- First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kg
- description
- 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.
- interventionNames
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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.
References
Publications (1)
- RESULTDavids 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