Efficacy of Axicabtagene Ciloleucel Compared to Standard of Care Therapy in Subjects With Relapsed / Refractory Diffuse Large B Cell Lymphoma

Status: Active

Description

The purpose of this study is to evaluate whether axicabtagene ciloleucel therapy improves the clinical outcome compared with standard of care second-line therapy in patients with relapsed / refractory diffuse large B-cell lymphoma (DLBCL).

Eligibility Criteria

Inclusion Criteria

  • Histologically proven DLBCL, including transformation from follicular lymphoma
  • Relapsed or refractory disease after first-line chemoimmunotherapy
  • Refractory disease is defined as no complete remission to first-line therapy; individuals who are intolerant to first-line therapy are excluded.
  • Progressive disease (PD) as best response to first-line therapy
  • Stable disease (SD) as best response after at least 4 cycles of first-line therapy
  • Partial response (PR) as best response after at least 6 cycles and biopsy-proven residual disease or disease progression ≤ 12 months from initiation of therapy
  • Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven relapse ≤ 12 months of initiating first-line therapy
  • Individuals must have received adequate first-line therapy including at a minimum:
  • Anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20 negative, and
  • An anthracycline containing chemotherapy regimen
  • No known history or suspicion of central nervous system involvement by lymphoma
  • Eastern cooperative oncology group (ECOG) performance status of 0 or 1
  • Adequate bone marrow function as evidenced by:
  • Absolute neutrophil count (ANC) ≥ 1000/uL
  • Platelet ≥ 75,000/uL
  • Absolute lymphocyte count ≥ 100/uL
  • Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by:
  • Creatinine clearance (Cockcroft Gault) ≥ 60 mL/min
  • Serum Alanine aminotransferase/Aspartate aminotransferase (ALT/AST) ≤ 2.5 Upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 mg/dl
  • Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an Echocardiogram (ECHO), and no clinically significant Electrocardiogram (ECG) findings
  • No clinically significant pleural effusion
  • Baseline oxygen saturation > 92% on room air

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
  • Received more than one line of therapy for DLBCL
  • History of autologous or allogeneic stem cell transplant
  • Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous antimicrobials for management.
  • Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive). If there is a positive history of treated hepatitis B or hepatitis C, the viral load must be undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing.
  • Individuals with detectable cerebrospinal fluid malignant cells or known brain metastases, or with a history of cerebrospinal fluid malignant cells or brain metastases.
  • History or presence of non-malignant central nervous system (CNS) disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
  • Presence of any indwelling line or drain. Dedicated central venous access catheter such as a Port-a-Cath or Hickman catheter are permitted.
  • History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, or other clinically significant cardiac diseases within 12 months of enrollment
  • History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment
  • History of autoimmune disease, requiring systemic immunosuppression and/or systemic disease modifying agents within the last 2 years
  • History of anti-CD19 or CAR-T therapy or history of prior randomization in ZUMA-7

Locations & Contacts

California

Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: In review
Contact: Rajneesh Reghunathan
Phone: 310-825-6969
Email: RReghunathan@mednet.ucla.edu
Palo Alto
Stanford Cancer Institute Palo Alto
Status: Active
Name Not Available
San Diego
University of California San Diego
Status: Active
Name Not Available

Florida

Tampa
Moffitt Cancer Center
Status: Active
Contact: Frederick Lundry Locke
Phone: 800-456-7121
Email: canceranswers@moffitt.org

Illinois

Chicago
Northwestern University
Status: In review
Name Not Available
University of Chicago Comprehensive Cancer Center
Status: Active
Name Not Available

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: Active
Name Not Available

Kansas

Kansas City
University of Kansas Cancer Center
Status: Active
Name Not Available
Westwood
University of Kansas Hospital-Westwood Cancer Center
Status: Active
Name Not Available

Maryland

Baltimore
University of Maryland / Greenebaum Cancer Center
Status: Active
Contact: Patricia Lesho
Phone: 410-328-2577
Email: plesho@umm.edu

Massachusetts

Boston
Brigham and Women's Hospital
Status: Active
Name Not Available
Dana-Farber Cancer Institute
Status: Active
Name Not Available

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: Active
Name Not Available

Minnesota

Rochester
Mayo Clinic
Status: Active
Name Not Available

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: Active
Name Not Available

New York

New York
Icahn School of Medicine at Mount Sinai
Status: Active
Name Not Available
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Miguel-Angel Perales
Phone: 212-639-8682
Email: peralesm@mskcc.org

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: Active
Name Not Available
Columbus
Ohio State University Comprehensive Cancer Center
Status: Active
Name Not Available

Pennsylvania

Philadelphia
Thomas Jefferson University Hospital
Status: Active
Name Not Available
Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: Active
Name Not Available

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: Active
Contact: Thomas C. Leonard-Martin
Email: Thomas.Leonard-Martin@vanderbilt.edu

Texas

Houston
M D Anderson Cancer Center
Status: Active
Name Not Available

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: Active
Name Not Available

Virginia

Charlottesville
University of Virginia Cancer Center
Status: Active
Name Not Available

Trial Objectives and Outline

This is a phase 3 randomized, open-label, multicenter study evaluating the efficacy of axicabtagene ciloleucel versus standard of care therapy in subjects with relapsed/refractory DLBCL. Adult subjects with relapsed/refractory DLBCL after first-line rituximab and anthracycline-based chemotherapy will be randomized in a 1:1 ratio to receive axicabtagene ciloleucel or standard of care second-line therapy. Standard of care will consist of a protocol-defined, platinum-based salvage combination chemotherapy regimen followed by high-dose therapy and autologous stem cell transplant in those who respond to salvage chemotherapy.

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
Kite, A Gilead Company

Trial IDs

Primary ID KTE-C19-107
Secondary IDs NCI-2018-00042, 2017-002261-22
Clinicaltrials.gov ID NCT03391466