Study of Safety and Efficacy of KTE-C19 in Combination With Atezolizumab in Adults With Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
ZUMA-6
A Phase 1-2 Multi-Center Study Evaluating the Safety and Efficacy of KTE-C19 in Combination With Atezolizumab in Subjects With Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
1 other identifier
interventional
37
1 country
5
Brief Summary
The primary objective of phase 1 is to evaluate the safety of KTE-C19 and atezolizumab combination regimens. The primary objective of phase 2 is to evaluate the efficacy of KTE-C19 and atezolizumab, as measured by complete response rate in participants with refractory diffuse large B-cell lymphoma (DLBCL). Participants who received an infusion of KTE-C19 will complete the remainder of the 15 year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968 (NCT05041309).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Sep 2016
Longer than P75 for phase_1
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 29, 2016
CompletedFirst Submitted
Initial submission to the registry
October 5, 2016
CompletedFirst Posted
Study publicly available on registry
October 6, 2016
CompletedResults Posted
Study results publicly available
June 26, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 12, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
January 12, 2023
CompletedMarch 6, 2024
February 1, 2024
6.3 years
October 5, 2016
June 8, 2020
February 13, 2024
Conditions
Outcome Measures
Primary Outcomes (2)
Phase 1: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
A DLT was defined as the following KTE-C19-related or ATZ-related events with an onset from immediately after the first ATZ infusion through 21 days after the first ATZ infusion: Grade 4 hematologic toxicity lasting \> 30 days (except lymphopenia or B-cell aplasia); All KTE-C19- or ATZ-related Grade 3 non-hematologic toxicities lasting for \> 7 days and all KTE-C19- or ATZ-related Grade 4 non-hematologic toxicities regardless of duration.
Baseline up to 21 days
Phase 1 and 2: Complete Response Rate (CRR)
CRR was assessed based on the International Working Group Revised Response Criteria for Malignant Lymphoma (Cheson, 2007), and was defined as the percentage of participants achieving a complete response (CR) as assessed by the study investigators. CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease.
From enrollment until first occurrence of CR or PR (maximum duration: 6.2 years)
Secondary Outcomes (17)
Phase 1 and 2: Objective Response Rate (ORR)
From enrollment until first occurrence of CR or PR (maximum duration: 6.2 years)
Phase 1 and 2: Duration of Response (DOR)
From the date of first confirmed objective response (CR or PR) to disease progression or death regardless of cause (maximum duration: 6.2 years)
Phase 1 and 2: Progression-Free Survival (PFS)
From the date of first KTE-C19 infusion to disease progression or death regardless of cause (maximum duration: 6.2 years)
Phase 1 and 2: Overall Survival (OS)
From the date of first KTE-C19 infusion to the date of death regardless of cause (maximum duration: 6.2 years)
Phase 1 and 2: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
Up to 1.8 years
- +12 more secondary outcomes
Study Arms (4)
Phase 1 Cohort 1: KTE-C19 + ATZ (After 21 Days of KTE-C19)
EXPERIMENTALParticipants received conditioning chemotherapy consisting of 30 mg/m\^2 fludarabine and 500 mg/m\^2 cyclophosphamide intravenous (IV) infusion per day for 3 days followed by KTE-C19 IV infusion at a target dose of 2 x 10\^6 anti-CD19 chimeric antigen receptor (CAR) T cells/kg followed by 4 doses of atezolizumab (ATZ) (1200 mg/dose) IV infusion every 21 days, beginning 21 days following KTE-C19.
Phase 1 Cohort 2: KTE-C19 + ATZ (After 14 Days of KTE-C19)
EXPERIMENTALParticipants received conditioning chemotherapy consisting of 30 mg/m\^2 fludarabine and 500 mg/m\^2 cyclophosphamide IV infusion per day for 3 days followed by KTE-C19 IV infusion at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg followed by 4 doses of ATZ (1200 mg/dose) IV infusion every 21 days, beginning 14 days following KTE-C19.
Phase 1 Cohort 3: KTE-C19 + ATZ (After 1 Day of KTE-C19)
EXPERIMENTALParticipants received conditioning chemotherapy consisting of 30 mg/m\^2 fludarabine and 500 mg/m\^2 cyclophosphamide IV infusion per day for 3 days followed by KTE-C19 IV infusion at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg followed by 4 doses of ATZ (1200 mg/dose) IV infusion every 21 days, beginning 1 day following KTE-C19.
Phase 2: KTE-C19 + ATZ (After 1 Day of KTE-C19)
EXPERIMENTALParticipants received conditioning chemotherapy consisting of 30 mg/m\^2 fludarabine and 500 mg/m\^2 cyclophosphamide IV infusion per day for 3 days followed by KTE-C19 IV infusion at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg followed by 4 doses of ATZ (1200 mg/dose) IV infusion every 21 days, beginning 1 day following KTE-C19.
Interventions
A single infusion of KTE-C19 CAR-T cells administered intravenously
Administered intravenously
Administered intravenously
Administered intravenously
Eligibility Criteria
You may qualify if:
- Histologically confirmed DLBCL
- Chemotherapy-refractory disease, defined as one or more of the following:
- Stable disease (duration of stable disease must be less than or equal to 6 months) or progressive disease as best response to most recent chemotherapy containing regimen
- Disease progression or recurrence less than or equal to 12 months of prior autologous stem cell transplantation (SCT)
- Individuals must have received adequate prior therapy including at a minimum:
- Anti-cluster of differentiate 20 (anti-CD20) monoclonal antibody unless investigator determines that tumor is CD20-negative; and
- an anthracycline containing chemotherapy regimen
- At least one measurable lesion per revised International Working Group (IWG) Response Criteria
- Age 18 years or older
- Eastern cooperative oncology group (ECOG) performance status of 0 or 1
- Adequate organ and bone marrow function
- All individuals or legally appointed representatives/caregivers, must personally sign and date the institutional review board (IRB)/independent ethics committee (IEC) approved consent form before initiating any study specific procedures or activities.
You may not qualify if:
- History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years
- History of allogeneic stem cell transplantation
- Prior CAR therapy or other genetically modified T cell therapy
- Clinically significant active infection
- Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive)
- Individuals with detectable cerebrospinal fluid malignant cells or brain metastases or with a history of cerebrospinal fluid malignant cells or brain metastases
- History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with central nervous system (CNS) involvement
- History of autoimmune disease. Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and participants with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible for this study.
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis per chest computed tomography (CT) scan at screening. History of radiation pneumonitis in the radiation field (fibrosis) is allowed.
- Prior treatment with Programmed Cell Death Ligand 1 (PD-L1) inhibitor, PD-1 inhibitor, anti-CTLA4, anti-CD137, anti-OX40 or other immune checkpoint blockade or activator therapy with the exception of Individuals who received atezolizumab in this study and are eligible for re-treatment
- Prior CD19 targeted therapy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Kite, A Gilead Companylead
- Genentech, Inc.collaborator
Study Sites (5)
City of Hope
Duarte, California, 91010, United States
Stanford Cancer Center
Palo Alto, California, 94305, United States
H Lee Moffitt Cancer Center
Tampa, Florida, 33612, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (3)
Jacobson CA, Locke FL, Miklos DB, Herrera AF, Westin JR, Lee J, et al. End of Phase 1 results for ZUMA-6: Axicabtagene ciloleucel (axi-cel) in combination with atezolizumab for the treatment of patients with refractory diffuse large B cell lymphoma. Presented at ASH, 2018.
BACKGROUNDLocke FL, Westin JR, Miklos DB, Herrera AF, Jacobson CA, Lee J, et al. Phase 1 results from ZUMA-6: Axicabtagene ciloleucel (axi-cel; KTE-C19) in combination with atezolizumab for the treatment of patients with refractory diffuse large B cell lymphoma. Presented at ASH, 2018, presentation #2628.
BACKGROUNDErnst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
PMID: 34515338DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Information
- Organization
- Kite, A Gilead Company
Study Officials
- STUDY DIRECTOR
Kite Study Director
Kite, A Gilead Company
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
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 5, 2016
First Posted
October 6, 2016
Study Start
September 29, 2016
Primary Completion
January 12, 2023
Study Completion
January 12, 2023
Last Updated
March 6, 2024
Results First Posted
June 26, 2020
Record last verified: 2024-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- 18 months after study completion
- Access Criteria
- A secured external environment with username, password, and RSA code.
Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy