Summary

for people ages 18 years and up (full criteria)
at San Diego, California and other locations
study started
estimated completion:
Dimitrios Tzachanis

Description

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.

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

Details

This is a phase 3 randomized, open-label, multicenter study evaluating the efficacy of axicabtagene ciloleucel versus standard of care therapy in subjects with relapsed/refractory DLBCL. Adult subjects with relapsed/refractory DLBCL after first-line rituximab and anthracycline-based chemotherapy will be randomized in a 1:1 ratio to receive axicabtagene ciloleucel or standard of care second-line therapy.

Standard of care will consist of a protocol-defined, platinum-based salvage combination chemotherapy regimen followed by high-dose therapy and autologous stem cell transplant in those who respond to salvage chemotherapy.

Keywords

Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Axicabtagene Ciloleucel Platinum-containing salvage chemotherapy (eg, R-ICE) followed by high dose therapy (eg, BEAM) and autologous stem cell transplant in responders.

Eligibility

For people ages 18 years and up

Key Inclusion Criteria:

  1. Histologically proven DLBCL, including transformation from follicular lymphoma
  2. Relapsed or refractory disease after first-line chemoimmunotherapy
  3. Refractory disease is defined as no complete remission to first-line therapy;subjects who are intolerant to first-line therapy are excluded.
  4. Progressive disease (PD) as best response to first-line therapy
  5. Stable disease (SD) as best response after at least 4 cycles of first-line therapy
  6. 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
  7. Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven relapse ≤ 12 months of initiating first-line therapy
  8. Subjects must have received adequate first-line therapy including at a minimum:
  9. Anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20 negative, and
  10. An anthracycline containing chemotherapy regimen
  11. No known history or suspicion of central nervous system involvement by lymphoma
  12. ECOG performance status of 0 or 1
  13. Adequate bone marrow function as evidenced by:
  14. ANC ≥ 1000/uL
  15. Platelet ≥ 75,000/uL
  16. Absolute lymphocyte count ≥ 100/uL
  17. Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by:
  18. Creatinine clearance (Cockcroft Gault) ≥ 60 mL/min
  19. Serum ALT/AST ≤ 2.5 ULN
  20. Total bilirubin ≤ 1.5 mg/dl
  21. Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an ECHO, and no clinically significant ECG findings
  22. No clinically significant pleural effusion
  23. 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. Subjects with detectable cerebrospinal fluid malignant cells or known brain metastases, or with a history of cerebrospinal fluid malignant cells or brain metastases.
  7. 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
  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 enrollment
  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

Locations

  • UC San Diego Moores Cancer Center accepting new patients
    San Diego California 92093-0698 United States
  • Banner MD Anderson Cancer Center accepting new patients
    Gilbert Arizona 85234 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Kite, A Gilead Company
ID
NCT03391466
Phase
Phase 3
Lead Scientist
Dimitrios Tzachanis
Study Type
Interventional
Last Updated
September 17, 2018