Relapsed/Refractory Chronic Lymphocytic Leukemia and Relapsed/Refractory Small Lymphocytic Lymphoma Clinical Trial
— ZUMA-8Official 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
| Verified date | October 2023 |
| Source | Gilead Sciences |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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).
| Status | Terminated |
| Enrollment | 16 |
| Est. completion date | November 18, 2022 |
| Est. primary completion date | February 12, 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| Italy | IRCCS Ospedale San Raffaele | Milano | |
| United States | Emory University | Atlanta | Georgia |
| United States | Dana Farber Cancer Institute | Boston | Massachusetts |
| United States | Cleveland Clinic - Taussig Cancer Institute | Cleveland | Ohio |
| United States | Ohio State University | Columbus | Ohio |
| United States | Baylor Cancer Hospital | Dallas | Texas |
| United States | Sarah Cannon - Denver | Denver | Colorado |
| United States | Hackensack University Medical Center | Hackensack | New Jersey |
| United States | MD Anderson Cancer Center | Houston | Texas |
| United States | University of California Los Angeles (UCLA) | Los Angeles | California |
| United States | Sarah Cannon Research Center | Nashville | Tennessee |
| United States | Vanderbilt University | Nashville | Tennessee |
| United States | Memorial Sloan-Kettering | New York | New York |
| United States | Fox Chase Cancer Center | Philadelphia | Pennsylvania |
| United States | Mayo Clinic - Arizona | Phoenix | Arizona |
| United States | Mayo Clinic | Rochester | Minnesota |
| United States | University of Rochester | Rochester | New York |
| United States | Washington University School of Medicine | Saint Louis | Missouri |
| United States | Swedish Cancer Institute | Seattle | Washington |
| United States | Stanford University | Stanford | California |
| United States | Moffitt Cancer Center | Tampa | Florida |
| United States | University of Kansas Cancer Center | Westwood | Kansas |
| Lead Sponsor | Collaborator |
|---|---|
| Kite, A Gilead Company |
United States, Italy,
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.
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | Objective Response Rate (ORR) Per Investigator Review Assessed by International Workshop on CLL (IWCLL) 2018 Criteria | 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. | First infusion date up to last follow up visit (maximum duration: 42 months) | |
| Secondary | Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) | 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. | First infusion date up to last follow up visit (maximum duration: 42 months) | |
| Secondary | Peak Level of Anti-CD19 CAR T-Cells in Blood | Peak was defined as the maximum number of CAR T cells measured post-infusion. | First infusion date up to 3 months post-infusion (approximately 3 months) |