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

Not Recruiting

Trial ID: NCT03391466


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).

Official Title

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

Stanford Investigator(s)

David Miklos
David Miklos

Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Rondeep Brar
Rondeep Brar

Clinical Associate Professor, Medicine - Hematology

Andrew Rezvani, M.D.
Andrew Rezvani, M.D.

Associate Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Michael Khodadoust
Michael Khodadoust

Assistant Professor of Medicine (Oncology) and of Dermatology

Lori Muffly
Lori Muffly

Associate Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Neel K. Gupta
Neel K. Gupta

Clinical Assistant Professor, Medicine - Oncology Clinical Assistant Professor, Medicine - Hematology

Lauren Maeda
Lauren Maeda

Clinical Associate Professor, Medicine - Oncology

Wen-Kai Weng, MD, PhD
Wen-Kai Weng, MD, PhD

Associate Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy) and, by courtesy, of Dermatology

Ranjana Advani
Ranjana Advani

Saul A. Rosenberg, MD, Professor of Lymphoma

Robert Lowsky
Robert Lowsky

Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)


Key Inclusion Criteria:

   1. Histologically proven large B-cell lymphoma including the following types defined by
   WHO 2016 (Swerdlow et al, 2016)

      - DLBCL not otherwise specified (ABC/GCB)

      - HGBL with or without MYC and BCL2 and/or BCL6 rearrangement

      - DLBCL arising from FL

      - T-cell/histiocyte rich large B-cell lymphoma

      - DLBCL associated with chronic inflammation

      - Primary cutaneous DLBCL, leg type

      - Epstein-Barr virus (EBV) + DLBCL

   2. 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

   3. 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

   4. No known history or suspicion of central nervous system involvement by lymphoma

   5. Eastern cooperative oncology group (ECOG) performance status of 0 or 1

   6. Adequate bone marrow function as evidenced by:

      - Absolute neutrophil count (ANC) ≥ 1000/uL

      - Platelet ≥ 75,000/uL

      - Absolute lymphocyte count ≥ 100/uL

   7. 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

   2. Received more than one line of therapy for DLBCL

   3. History of autologous or allogeneic stem cell transplant

   4. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or
   requiring intravenous antimicrobials for management.

   5. 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.

   6. Individuals with detectable cerebrospinal fluid malignant cells or known brain
   metastases, or with a history of cerebrospinal fluid malignant cells or brain

   7. 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

   8. Presence of any indwelling line or drain. Dedicated central venous access catheter
   such as a Port-a-Cath or Hickman catheter are permitted.

   9. 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

10. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of

11. History of autoimmune disease, requiring systemic immunosuppression and/or systemic
   disease modifying agents within the last 2 years

12. 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


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

biological: Axicabtagene Ciloleucel

drug: Cyclophosphamide

drug: Fludarabine

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Sharon Claire

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