Study Details

PROTOCOL SUMMARY

The goal of this clinical study is to assess 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).

Participation Requirements

Age

18 Years +

Sex

All

Healthy Volunteers

Medical Condition

Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Gender

N/A

Date

January 2018 - March 2021

Study Type

Interventional

Study Phase

Phase 3

Product

Axicabtagene Ciloleucel, Platinum-containing salvage chemotherapy (eg, R-ICE) followed by high dose therapy (eg, BEAM) and autologous stem cell transplant in responders., Cyclophosphamide, Fludarabine

Eligibility Information

Inclusion Criteria

Histologically proven large B-cell lymphoma including the following types defined by World Health Organization (WHO) 2016.
Diffuse large B-cell lymphoma (DLBCL) not otherwise specified activated B-cell/ germinal center B-cell (ABC/GCB).
High-grade B-cell lymphoma (HGBL) with or without myelocytomatosis oncogene (MYC) and B-cell lymphoma (BCL) 2 and/or BCL6 rearrangement.
DLBCL arising from follicular lymphoma (FL).
T-cell/histiocyte rich large B-cell lymphoma.
DLBCL associated with chronic inflammation.
Primary cutaneous DLBCL, leg type.
Epstein-Barr virus (EBV) + DLBCL.
Relapsed or refractory disease after first-line chemoimmunotherapy.
Refractory disease 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 (eg, 4 cycles of R-CHOP).
Partial response (PR) as best response after at least 6 cycles and biopsy-proven residual disease or disease progression ≤ 12 months of therapy.
Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven relapse ≤ 12 months of first-line therapy.
Individuals must have received adequate first-line therapy including at a minimum:
Anti-Cluster of Differentiation antigen (CD) 20 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.
Note: Other protocol defined Inclusion/Exclusion criteria may apply

Locations

Locations (72)

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States, 85234

Mayo Clinic Hospital

Phoenix, Arizona, United States, 85054

UC San Diego Moores Cancer Center

La Jolla, California, United States, 92093

UCLA

Santa Monica, California, United States, 90404

Stanford Cancer Institute

Stanford, California, United States, 94305

University of Miami Hospital and Clinics/Sylvester Comprehensive Cancer Center

Miami, Florida, United States, 33136

Moffitt Cancer Center

Tampa, Florida, United States, 12902

Northwestern University

Chicago, Illinois, United States, 60612

University of Chicago Medical Center

Chicago, Illinois, United States, 60637

University of Iowa Hospitals and Clinincs

Iowa City, Iowa, United States, 52242

The University of Kansas Cancer Center

Kansas City, Kansas, United States, 66160

University of Maryland, Greenbaum Comprehensive Cancer Center

Baltimore, Maryland, United States, 21201

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

Mayo Clinic, Patient Location

Rochester, Minnesota, United States, 55905

Washington University School of Medicine

Saint Louis, Missouri, United States, 63130

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

Memorial Sloan Kettering Cancer Center

New York, New York, United States, 10021

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10029

University of Rochester Medical Center

Rochester, New York, United States, 14642

Cleveland Clinic

Cleveland, Ohio, United States, 44195

James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States, 43210

Thomas Jefferson University

Philadelphia, Pennsylvania, United States, 19107

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States, 15213

Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37203

Henry-Joyce Cancer Center

Nashville, Tennessee, United States, 37232

The University of Texas, MD Anderson Cancer Center

Houston, Texas, United States, 77030

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, United States, 84112

University of Virginia Health System

Charlottesville, Virginia, United States, 22908

Swedish Cancer Institute

Seattle, Washington, United States, 98104

Peter MacCallum Cancer Center

Melbourne, Victoria, Australia, 3000

Universitatsklinikum Graz, Division of Hematology

Graz, Austria, 6020

Medizinische Universitat Innsbruck, Innere Medizin V - Hamatologie und Onkologie

Innsbruck, Austria, 6020

Cliniques Universiaires Saint-Luc

Brussels, Belgium

UZ Gasthuisberg

Leuven, Belgium

Vancouver General Hospital

Vancouver, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada, R3E 0V9

Uninversity Health Network - Princess Margaret Cancer Center

Toronto, Ontario, Canada, M5G 2M9

McGill University Health Center

Montreal, Quebec, Canada, H4A 3J1

QEII Health Sciences Centre

Halifax, Canada, B3H 2Y9

Centre Integre Universitaire de Sante et Services Sociaux de l'Est-de-l'lle-de-Montreal / Hopital Maisonneuve-Rosemont

Montréal, Canada, H1T 2M4

The Ottawa Hospital - General Campus

Ottawa, Canada, K1H 8L6

CHU de Quebec-Universite Laval, Hopital de L'Enfante-Jesus

Québec, Canada, G1J 1Z4

CHRU de Lille - Hopital Claude Huriez

Lille cedex, France, 59037

Hopital Saint-Louis

Paris, France, 75010

Centre Hospitalier Lyon-Sud - Service d'Hematologie clinique

Pierre Benite, France, 69495

Centre Hospitalier Universitaire de Rennes - Hopital Pontchaillou

Rennes, France, 35033

Universitäts-klinikum Dresden

Dresden, Germany, 01307

Universitatsmedizin Gottingen

Göttingen, Germany, 37075

Universitatsklinikum Hamburg-Eppendorf

Hamburg, Germany, 20246

Universitätsklinikum Heidelberg

Heidelberg, Germany, 69120

Universitäts-klinikum Würzburg

Würzburg, Germany, 97080

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel, 6423906

Instituto di Ematologia "L. e A. Seragnoli" - Dipartimento di Medicina Specialistica Diagnostica e Sperimentale

Bologna, Italy, 40138

IRCCS Ospedale San Raffaele di Milano

Milano, Italy, 20132

Academic Medical Center

Amsterdam, Netherlands, 1105 AZ

University Medical Center Groningen

Groningen, Netherlands, 9700 RB

Erasmus Medical Center

Rotterdam, Netherlands, 3011PL

University Medical Center Utrecht

Utrecht, Netherlands

Hospital Clinic de Barcelona

Barcelona, Spain, 08036

Institut Catala d'Oncologia

Barcelona, Spain, 08908

Hospital Universitario La Paz

Madrid, Spain, 28046

Clinica Universidad de Navarra

Pamplona, Spain, 31008

Hospital Universitario de Salamanca

Salamanca, Spain, 37007

Uppsala Akademiska Sjukhus

Uppsala, Sweden, 75185

IOSI, OSpedale Regionale Bellinzona e Valli

Bellinzona, Switzerland, 6500

University Hospital Zurich

Zürich, Switzerland, 8091

University Hospitals Birmingham NHS Foundation Trust

Birmingham, United Kingdom, B15 2GW

Barts Health NHS Trust

London, United Kingdom, EC1A 7BE

University College London Hospitals NHS Foundation Trust

London, United Kingdom, NW3 2QG

The Christie NHS Foundation Trust

Manchester, United Kingdom, M20 4BX

The Royal Marsden NHS Foundation Trust

Sutton, United Kingdom, SM2 5PT

Study of Effectiveness of Axicabtagene Ciloleucel Compared to Standard of Care Therapy in Patients With Relapsed/Refractory Diffuse Large B Cell Lymphoma (ZUMA-7)

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