Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Participants With High-Risk Large B-Cell Lymphoma (ZUMA-12)

• ClinicalTrials.gov Identifier: NCT03761056
• Recruitment Status: Active, not recruiting
• First Posted: December 3, 2018
• Last Update Posted: June 3, 2021
• Sponsor: Kite, A Gilead Company
• Information provided by (Responsible Party): Gilead Sciences ( Kite, A Gilead Company )

Study Description

Brief Summary:

The primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in participants with high-risk large B-cell lymphoma.

Condition or disease	Intervention/treatment	Phase
B-cell Lymphoma	Biological: Axicabtagene Ciloleucel; Drug: Fludarabine; Drug: Cyclophosphamide	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Multicenter Study Evaluating the Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Subjects With High-Risk Large B-Cell Lymphoma (ZUMA-12)
• Actual Study Start Date: January 29, 2019
• Actual Primary Completion Date: May 4, 2021
• Estimated Study Completion Date: March 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Axicabtagene Ciloleucel; Participants will receive cyclophosphamide and fludarabine conditioning chemotherapy followed by the investigational treatment, axicabtagene ciloleucel	Biological: Axicabtagene Ciloleucel; A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously; Other Name: Yescarta®; Drug: Fludarabine; Administered according to package insert; Drug: Cyclophosphamide; Administered according to package insert

Outcome Measures

Primary Outcome Measures :

1. Complete Response (CR) Rate [ Time Frame: Up to 2 years ]
   Complete Response rate is defined as the incidence of a CR per the Lugano Classification (Cheson et al, 2014), as determined by study investigators.

Secondary Outcome Measures :

1. Objective Response Rate (ORR) [ Time Frame: Up to 2 years ]
   ORR is defined as the incidence of either a CR or a partial response (PR) per the Lugano Classification as determined by study investigators.
2. Duration of Response (DOR) [ Time Frame: Up to 2 years ]
   DOR is defined only for participants who experience an objective response after axicabtagene ciloleucel infusion and is the time from the first objective response to disease progression or death from any cause.
3. Event-Free Survival (EFS) [ Time Frame: Up to 5 years ]
   EFS is defined as the time from the axicabtagene ciloleucel infusion date to the earliest date of disease progression, commencement of subsequent new anti-lymphoma therapy including stem cell transplant (SCT), or death from any cause.
4. Progression-Free Survival (PFS) [ Time Frame: Up to 2 years ]
   PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression or death from any cause.
5. Overall Survival (OS) [ Time Frame: Up to 5 years ]
   OS is defined as the time from axicabtagene ciloleucel infusion to the date of death from any cause.
6. Percentage of participants experiencing adverse events and Clinical Significant Changes in Safety Lab Values [ Time Frame: Up to 2 years ]
7. Relapse with Central Nervous Disease (CNS) Disease [ Time Frame: Up to 5 years ]
   Relapse with CNS disease is defined as the time from the axicabtagene ciloleucel infusion date to the earliest date of CNS involvement with lymphoma as determined by typical symptoms, CSF evaluation, and/or diagnostic imaging.
8. Levels of anti-CD19 CAR T cells in blood [ Time Frame: Up to 1 year ]
9. Levels of cytokines in serum [ Time Frame: Up to 1 year ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• Histologically confirmed large B-cell lymphoma
• High-grade large B-cell lymphoma
• Individuals must have a positive interim positron emission tomography (PET) per Cheson, 2014 (Deauville PET score of 4 or 5) after 2 cycles (PET2+) of chemoimmunotherapy
• No evidence, suspicion and/or history of CNS involvement of lymphoma
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Absolute neutrophil count ≥ 1000/μL
• Platelet count ≥ 75,000/μL
• Absolute lymphocyte count ≥ 100/μL

• Adequate renal, hepatic, pulmonary, and cardiac function defined as:

  • Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min
  • Serum alanine aminotransferase (ALT/AST) ≤ 2.5 upper limit of normal (ULN)
  • Total bilirubin ≤1.5 mg/dL, except in individuals with Gilbert's syndrome
• Cardiac ejection fraction ≥ 50% , no evidence of pericardial effusion as determined by an ECHO, and no clinically significant ECG findings
• No clinically significant pleural effusion
• Baseline oxygen saturation > 92% on room air

Key Exclusion Criteria:

• History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg cervix, bladder, breast) unless disease free for at least 3 years
• History of Richter's transformation of chronic lymphocytic leukemia or primary mediastinal B-cell lymphoma
• History of autologous or allogeneic stem cell transplant
• Prior CD19-targeted therapy
• Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy
• Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management
• History of HIV infection or acute or chronic active hepatitis B or C infection
• Presence of any indwelling line or drain dedicated central venous access catheters, such as a Port-a-Cath or Hickman catheter, are permitted
• Individuals with detectable cerebrospinal fluid malignant cells, brain metastases, or active CNS lymphoma
• History or presence of CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
• History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
• History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

United States, Arizona

Banner Health MD Anderson Cancer Center

Gilbert, Arizona, United States, 85234

United States, California

City of Hope

Duarte, California, United States, 91010-3012

UCLA

Los Angeles, California, United States, 90095

United States, Florida

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States, 33612

United States, Illinois

University of Chicago

Chicago, Illinois, United States, 606337

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, Tennessee

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

United States, Texas

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

United States, Washington

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States, 98109

Australia, Victoria

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia, 3000

Canada

Ottawa Hospital

Ottawa, Canada, K1H 8L6

France

Hopital Saint Louis

Paris, France, 75475

Sponsors and Collaborators

Kite, A Gilead Company

Investigators

• Study Director: Kite Study Director; Kite, A Gilead Company

More Information

• Responsible Party: Kite, A Gilead Company
• ClinicalTrials.gov Identifier: NCT03761056
• Other Study ID Numbers: KTE-C19-112; 2019-002291-13 ( EudraCT Number )
• First Posted: December 3, 2018
• Last Update Posted: June 3, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lymphoma; Lymphoma, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Cyclophosphamide; Fludarabine; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists