Clinical Trial 19341

Cancer Type: Immunotherapy
Interventions:Axicabtagene Ciloleucel (KTE-C19); KTE-C19; MESNA; cyclophosphamide; cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

Study Type: Treatment
Phase of Study: Phase III
Investigators:

  • Frederick Locke

Overview

Study 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)

Summary

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 DLBCL.

Objective

Primary Objective: To determine if axicabtagene ciloleucel is superior to SOC as measured by event-free survival (EFS), as determined by blinded central review. Secondary Objectives: To evaluate the effect of axicabtagene ciloleucel compared to SOC on objective response rate (ORR), as determined by blinded central review. To evaluate the effect of axicabtagene ciloleucel compared to SOC on overall survival (OS). To evaluate the effect of axicabtagene ciloleucel compared to SOC on progression-free survival (PFS). To evaluate the effect of axicabtagene ciloleucel compared to SOC on duration of response (DOR) and duration of complete response among responding subjects, as determined by blinded central review. To evaluate the safety of axicabtagene ciloleucel compared to SOC. To evaluate the effect of axicabtagene ciloleucel on patient reported outcomes (PROs) and quality of life (QoL) compared to SOC. Exploratory Objectives: Explore mechanisms of resistance to treatment with axicabtagene ciloleucel. Evaluate mechanistic aspects and reversibility of toxicities with axicabtagene ciloleucel. Explore molecular and histologic characteristics of the tumor microenvironment. Evaluate impact of disease and treatment on work productivity and activity.

Inclusion Criteria

  • Histologically proven Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL), including transformation from follicular lymphoma
  • Relapsed or refractory disease after first-line chemoimmunotherapy. Refractory disease is defined as no complete remission to first-line therapy; patients 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; Partial response (PR) as best response after at least 6 cycles and biopsy-proven residual disease or disease progression ≤ 12 months from initiation of therapy. Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven relapse ≤ 12 months of initiating first-line therapy.
  • Participants 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.
  • 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: 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 ALT/AST ≤ 2.5 ULN; Total bilirubin ≤ 1.5 mg/dl; Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an ECHO, and no clinically significant 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 (e.g., 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.
  • 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 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