LAST UPDATED
June 04, 2024
Clinicaltrials.gov ID
EudraCT ID
OVERVIEW
A Phase 1/2 Multicenter Study Evaluating the Safety and Efficacy of KTE-C19 in Adults With Refractory Aggressive Non-Hodgkin Lymphoma (ZUMA-1)
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.
View moreParticipation requirements
Age
18 years +
Sex
All
Healthy Volunteers
No
Age
18 years +
Sex
All
Healthy Volunteers
No
Study details
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 - July 2023
Study Type
Interventional
Study Phase
Phase 1, Phase 2
Product
Axicabtagene Ciloleucel, Fludarabine, Cyclophosphamide, Levetiracetam, Tocilizumab, Dexamethasone, High-dose methylprednisolone, Bendamustine, Rituximab, Doxorubicin, Prednisone, Vincristine, Ifosfamide, Carboplatin, Etoposide, Gemcitabine, Oxaliplatin, Cisplatin, Methylprednisolone
Eligibility information
Inclusion criteria
- 1. 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)
- 2. 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
- 3. Individuals must have received adequate prior therapy including at a minimum:
- Anti-cluster of differentiate 20 (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.
- 4. At least one measurable lesion per revised international working group (IWG Response Criteria
- 5. Eastern cooperative oncology group (ECOG) performance status of 0 or 1
- 6. Absolute neutrophil count (ANC) ≥ 1000/microliters (uL)
- 7. Absolute lymphocyte count ≥ 100/uL
- 8. Platelet count ≥ 75,000/uL
- 9. 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
- 10. 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.
- 11. Relapsed or refractory large B-cell lymphoma including DLBCL, PMBCL, TFL, and HGBCL after two systemic lines of therapy
- K
Exclusion criteria
- 1. 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
- 2. History of allogeneic stem cell transplantation
- 3. Prior chimeric antigen receptor (CAR) therapy or other genetically modified T cell therapy
- 4. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management. Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment
- 5. 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
- 6. 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
- 7. 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
University of California San Diego (UCSD)
La Jolla, California, United States, 92093-0820
University of California Los Angeles (UCLA)
Santa Monica, California, United States, 90404
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
Washington University School of Medicine
St Louis, Missouri, United States, 63110
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Cleveland Clinic - Taussig Cancer Institute
Cleveland, Ohio, United States, 44195
Sarah Cannon-Methodist Healthcare System - San Antonio
San Antonio, Texas, United States, 78229
Vancouver General Hospital
Vancouver, British Columbia, Canada, V5Z 1M9
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