Study Details

PROTOCOL SUMMARY

This study will be separated into 3 distinct phases designated as the Phase 1 study, Phase 2 pivotal study (Cohort 1 and Cohort 2), and Phase 2 safety management study (Cohort 3 and Cohort 4, Cohort 5 and Cohort 6). The primary objectives of this study are: Phase 1 Study: Evaluate the safety of axicabtagene ciloleucel regimens Phase 2 Pivotal Study; Evaluate the efficacy of axicabtagene ciloleucel Phase 2 Safety Management Study: Assess the impact of prophylactic regimens or earlier interventions on the rate and severity of cytokine release syndrome (CRS) and neurologic toxicities Subjects 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.

Participation Requirements

Age

18 Years +

Sex

All

Healthy Volunteers

Medical Condition

Refractory Diffuse Large B Cell Lymphoma (DLBCL), Relapsed Diffuse Large B-Cell Lymphoma, Transformed Follicular Lymphoma (TFL), Primary Mediastinal B-cell Lymphoma (PMBCL), High Grade B-cell Lymphoma (HGBCL)

Gender

N/A

Date

April 2015 - September 2020

Study Type

Interventional

Study Phase

Phase 1, Phase 2

Product

Axicabtagene Ciloleucel, Fludarabine, Cyclophosphamide

Eligibility Information

Inclusion Criteria

Histologically confirmed:
Diffuse Large B Cell Lymphoma (DLBCL)
Primary Mediastinal Large B Cell Lymphoma (PMBCL)
Transformation Follicular Lymphoma (TFL)
High grade B-cell lymphoma (HGBCL)
Chemotherapy-refractory disease, defined as one of more of the following:
No response to last line of therapy i. Progressive disease (PD) as best response to most recent therapy regimen ii. Stable disease (SD) as best response to most recent therapy with duration no longer than 6 month from last dose of therapy OR
Refractory post-autologous stem cell transplant (ASCT) i. Disease progression or relapsed less than or equal to 12 months of ASCT (must have biopsy proven recurrence in relapsed individuals) ii. If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy
Individuals must have received adequate prior therapy including at a minimum:
anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20-negative and
an anthracycline containing chemotherapy regimen
for individual with transformed FL must have chemorefractory disease after transformation to DLBCL.
At least one measurable lesion per revised IWG Response Criteria
Eastern cooperative oncology group (ECOG) performance status of 0 or 1
Absolute neutrophil count (ANC) ≥ 1000/uL
Absolute lymphocyte count ≥ 100/uL
Platelet count ≥ 75,000/uL
Adequate renal, hepatic, pulmonary and cardiac function defined as:
Creatinine clearance (as estimated by Cockcroft Gault) > 60 mL/min
Serum alanine aminotransferase (ALT)/aspartate aminotransferase (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 echocardiogram (ECHO), and no clinically significant pleural effusion
Baseline oxygen saturation >92% on room air
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.
Relapsed or refractory large B-cell lymphoma including DLBCL, PMBCL, TFL, and HGBCL after two systemic lines of therapy

Exclusion Criteria

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
Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment
History of human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection. Individuals with history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines
Individuals with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases
History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations

Locations (36)

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States, 85234

City of Hope

Duarte, California, United States, 91010-3012

University of California San Diego (UCSD)

La Jolla, California, United States, 92093-0820

Stanford University

Palo Alto, California, United States, 94305

University of California Los Angeles (UCLA)

Santa Monica, California, United States, 90404

Sarah Cannon - Denver

Denver, Colorado, United States, 80218

University of Miami

Miami, Florida, United States, 33136

Moffitt Cancer Center

Tampa, Florida, United States, 33612

Loyola University Medical Center

Maywood, Illinois, United States, 60153

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States, 52242

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215

Karmanos Cancer Center

Detroit, Michigan, United States, 48201

Mayo Clinic

Rochester, Minnesota, United States, 55905

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

University of Nebraska

Omaha, Nebraska, United States, 68198-7680

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

Montefiore Medical Center

Bronx, New York, United States, 10467

University of Rochester

Rochester, New York, United States, 14642

Cleveland Clinic - Taussig Cancer Institute

Cleveland, Ohio, United States, 44195

Sarah Cannon - Tennesee

Nashville, Tennessee, United States, 37203

Vanderbilt University

Nashville, Tennessee, United States, 37232

MD Anderson Cancer Center

Houston, Texas, United States, 77030-4000

Sarah Cannon-Methodist Healthcare System - San Antonio

San Antonio, Texas, United States, 78229

Vancouver General Hospital

Vancouver, British Columbia, Canada, V5Z 1M9

Princess Margaret

Toronto, Ontario, Canada, M5G 2M9

Hopital Saint Louis

Paris, France, 75475

Hopital Haut-Leveque

Pessac, France, 44035

CHU de Rennes

Rennes, France, 35033

Universitätsklinik Dresden

Dresden, Germany, 01307

University Hospital of Essen

Essen, Germany, 45147

Universitaetsklinikum Wuerzburg

Würzburg, Germany, 97080

Tel Aviv Souraski Medical Center

Tel Aviv, Israel, 64239

Academisch Medisch Centrum

Amsterdam, Netherlands

University Medical Center Groningen

Groningen, Netherlands, 9700 RB

Erasmus MC

Rotterdam, Netherlands, 3015 CE

University Medical Center Utrecht

Utrecht, Netherlands, 3584 CX

Study Evaluating the Safety and Efficacy of KTE-C19 in Adult Participants With Refractory Aggressive Non-Hodgkin Lymphoma (ZUMA-1)

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