Purpose

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).

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Histologically proven large B-cell lymphoma including the following types defined by WHO 2016 (Swerdlow et al, 2016)
  2. DLBCL not otherwise specified (ABC/GCB)
  3. HGBL with or without MYC and BCL2 and/or BCL6 rearrangement
  4. DLBCL arising from FL
  5. T-cell/histiocyte rich large B-cell lymphoma
  6. DLBCL associated with chronic inflammation
  7. Primary cutaneous DLBCL, leg type
  8. Epstein-Barr virus (EBV) + DLBCL
  9. Relapsed or refractory disease after first-line chemoimmunotherapy
  10. Refractory disease defined as no complete remission to first-line therapy; individuals who are intolerant to first-line therapy are excluded.
  11. Progressive disease (PD) as best response to first-line therapy
  12. Stable disease (SD) as best response after at least 4 cycles of first-line therapy (eg, 4 cycles of R-CHOP)
  13. Partial response (PR) as best response after at least 6 cycles and biopsy-proven residual disease or disease progression ≤ 12 months of therapy
  14. Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven relapse ≤ 12 months of first-line therapy
  15. Individuals must have received adequate first-line therapy including at a minimum:
  16. Anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20 negative, and
  17. An anthracycline containing chemotherapy regimen
  18. No known history or suspicion of central nervous system involvement by lymphoma
  19. Eastern cooperative oncology group (ECOG) performance status of 0 or 1
  20. Adequate bone marrow function as evidenced by:
  21. Absolute neutrophil count (ANC) ≥ 1000/uL
  22. Platelet ≥ 75,000/uL
  23. Absolute lymphocyte count ≥ 100/uL
  24. Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by:
  25. Creatinine clearance (Cockcroft Gault) ≥ 60 mL/min
  26. Serum Alanine aminotransferase/Aspartate aminotransferase (ALT/AST) ≤ 2.5 Upper limit of normal (ULN)
  27. Total bilirubin ≤ 1.5 mg/dl
  28. Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an Echocardiogram (ECHO), and no clinically significant Electrocardiogram (ECG) findings
  29. No clinically significant pleural effusion
  30. Baseline oxygen saturation > 92% on room air

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 metastases.
  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 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

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Two arms, SOC and experimental treatment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Axicabtagene Ciloleucel Treatment
  • Biological: Axicabtagene Ciloleucel
    A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously following a conditioning chemotherapy regimen of fludarabine and cyclophosphamide
    Other names:
    • KTE-C19
    • axi-cel
  • Drug: Cyclophosphamide
    Administered intravenously
  • Drug: Fludarabine
    Administered intravenously
Active Comparator
Standard of Care Therapy
  • Drug: Platinum-containing salvage chemotherapy (eg, R-ICE) followed by high dose therapy (eg, BEAM) and autologous stem cell transplant in responders.
    Platinum-containing salvage chemotherapy (R-ICE, R-DHAP, R-ESHAP, or R-GDP as selected by treating investigator) followed by high dose therapy (eg, BEAM) and autologous stem cell transplant in responders.

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35233

More Details

NCT ID
NCT03391466
Status
Recruiting
Sponsor
Kite, A Gilead Company

Study Contact

Medical Information
1-844-454-5483(1-844-454-KITE)
medinfo@kitepharma.com

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.