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

Trial ID or NCT#

NCT03391466

Status

not recruiting iconNOT RECRUITING

Purpose

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).

Official Title

A Phase 3, Randomized, Open-Label Study Evaluating the Efficacy of Axicabtagene Ciloleucel Versus Standard of Care Therapy in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma (ZUMA-7)

Eligibility Criteria

Ages Eligible for Study: Older than 18 Years
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Inclusion Criteria:
  1. - 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. Key
Exclusion Criteria:
  1. - 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
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Investigator(s)

David Miklos
David Miklos
Blood and marrow transplant specialist, Blood and marrow transplant specialist, Hematologist, Medical oncologist
Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)
Rondeep Brar
Rondeep Brar
Hematologist-Oncologist
Clinical Associate Professor, Medicine - Hematology
Andrew Rezvani, M.D.
Andrew Rezvani, M.D.
Blood and marrow transplant specialist, Blood and marrow transplant specialist, Medical oncologist
Associate Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)
Michael Khodadoust
Michael Khodadoust
Lymphoma specialist, Cutaneous oncology specialist, Hematologist, Hematologist-Oncologist
Assistant Professor of Medicine (Oncology) and of Dermatology
Lori Muffly
Lori Muffly
Hematologist, Blood and marrow transplant specialist, Blood and marrow transplant specialist, Hematologist-Oncologist
Associate Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)
Neel K. Gupta
Neel K. Gupta
Hematologist-Oncologist
Clinical Associate Professor, Medicine - Oncology Clinical Assistant Professor, Medicine - Hematology
Wen-Kai Weng, MD, PhD
Wen-Kai Weng, MD, PhD
Blood and marrow transplant specialist, Blood and marrow transplant specialist, Lymphoma specialist, Medical oncologist, Multiple myeloma specialist
Associate Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy) and, by courtesy, of Dermatology
Ranjana Advani
Ranjana Advani
Lymphoma specialist, Hematologist-Oncologist
Saul A. Rosenberg, MD, Professor of Lymphoma
Robert Lowsky
Robert Lowsky
Blood and marrow transplant specialist, Hematologist, Blood and marrow transplant specialist
Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)
Robert Negrin
Robert Negrin
Blood and marrow transplant specialist, Hematologist, Blood and marrow transplant specialist
Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)
Lauren Maeda
Lauren Maeda
Hematologist, Lymphoma specialist, Hematologist-Oncologist
Clinical Associate Professor, Medicine - Oncology

Contact us to find out if this trial is right for you.

Contact

Sharon Claire
650-721-4091

View on ClinicalTrials.gov