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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Relapsed/Refractory Chronic Lymphocytic Leukemia and Relapsed/Refractory Small Lymphocytic Lymphoma
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2018-08-09
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)
timeFrame: 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:
measure: Objective Response Rate (ORR) Per Investigator Review Assessed by International Workshop on CLL (IWCLL) 2018 Criteria
timeFrame: First infusion date up to last follow up visit (maximum duration: 42 months)
measure: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)
timeFrame: First infusion date up to last follow up visit (maximum duration: 42 months)
measure: Peak Level of Anti-CD19 CAR T-Cells in Blood
timeFrame: First infusion date up to 3 months post-infusion (approximately 3 months)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic - Arizona
state: Arizona
city: Los Angeles
country: United States
facility: University of California Los Angeles (UCLA)
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Denver
country: United States
facility: Sarah Cannon - Denver
state: Colorado
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan-Kettering
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic - Taussig Cancer Institute
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: Baylor Cancer Hospital
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
Study officials:
affiliation: Kite, A Gilead Company
name: Kite Study Director
role: STUDY_DIRECTOR
References:
citation: 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.