A Study to Compare Axicabtagene Ciloleucel With Standard of Care Therapy as First-line Treatment in Participants With High-risk Large B-cell Lymphoma

• Status: Not yet recruiting
• Trial end date: 2031-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The goal of this study is to find out if the experimental product, axi-cel, is safe and effective in treating your lymphoma, compared to standard of care (SOC) therapy chemotherapy), which includes either R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) or DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kite, A Gilead Company
• Treatments: Cyclophosphamide; Doxorubicin; Etoposide; Fludarabine; Prednisone; Rituximab; Vincristine

Criteria

Key Inclusion Criteria:

• Histologically confirmed large B cell lymphoma (LBCL) based on 2016 World Health Organization (WHO) classification by local pathology lab assessment, including of the following:

• Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS)

• High-grade B-cell lymphoma (HGBL) (including HGBL with MYC and BCL2 and/or BCL6 rearrangements (DHL/THL) based on Fluorescence in situ hybridization (FISH) analysis, and High-grade B cell lymphoma not otherwise specified (HGBL-NOS).

• Note: Transformed DLBCL from follicular lymphoma or from marginal zone lymphoma is eligible if no prior treatment with anthracycline-containing regimen

• High-risk disease defined as an International Prognostic Index (IPI) score of 4 or 5 at initial diagnosis.

• Ann Arbor Stage III or IV disease.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of randomization.

• Note: ECOG > 2 at diagnosis is acceptable.

• Have received only 1 cycle of rituximab plus chemotherapy (R-chemotherapy).

• Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function as indicated by:

• Absolute neutrophil count (ANC) ≥ 1000/μL

• Platelet count ≥ 75,000/μL

• Absolute lymphocyte count ≥ 100/μL

• Creatinine clearance (as estimated by any local institutional method) ≥ 60 mL/minute

• Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels

≤ 2.5 × upper limit of normal (ULN) or ≤ 5 x ULN if documented liver involvement of lymphoma f) Total bilirubin ≤ 1.5 mg/dL, except in participants with Gilbert's Syndrome or documented LBCL liver or pancreatic involvement where ≤ 3.0 times the ULN

• Left ventricular ejection fraction (LVEF) ≥ 50% and no evidence of clinically significant pericardial effusion, and no clinically significant abnormal electrocardiogram (ECG) findings

• No evidence of Grade 2 (per Common Terminology Criteria for Adverse Events [CTCAE] 5.0) or greater pleural effusion or ascites (subjects with Grade 1 ascites or pleural effusion are eligible)

• Baseline oxygen saturation > 92% on room air

• Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential).

Key Exclusion Criteria:

• The following WHO 2016 subcategories by local assessment.

• T-cell/histiocyte-rich LBCL.

• Primary DLBCL of the central nervous system (CNS).

• Primary mediastinal (.thymic) LBCL.

• B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma.

• Burkitt lymphoma.

• Presence of detectable cerebrospinal fluid (CSF)-malignant cells, brain metastases, or a history of CNS involvement of lymphoma.

• Presence of cardiac atrial or ventricular lymphoma involvement.

• Any prior treatment for LBCL other than the 1 cycle of R-chemotherapy.

• History of severe immediate hypersensitivity reaction to any of the agents used in this study, including the lymphodepletion chemotherapy (cyclophosphamide or fludarabine)

• Presence of CNS disorder such as dementia, autoimmune disease with CNS involvement, cerebral edema with confirmed structural defects by appropriate imaging, or seizure disorders requiring active anticonvulsive medication. History of stroke, transient ischemic attack, or posterior reversible encephalopathy syndrome (PRES) within 12 months prior to enrollment.

• History of acute or chronic active hepatitis B or C infection. 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.

• Positive for human immunodeficiency virus (HIV) unless taking appropriate anti-HIV medications, with an undetectable viral load by PCR and with a cluster of differentiation 4 (CD4) count > 200 cells/uL.

• Medical conditions likely to interfere with assessment of safety or efficacy of study treatment. Please refer to protocol for further details.

• 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 disease within 12 months before enrollment.

• History of any medical condition including but not limited to autoimmune disease (eg, Crohn's disease, rheumatoid arthritis, systemic lupus) requiring maintenance systemic immunosuppression/systemic disease modifying agents within the last 2 years. Endocrine conditions that require maintenance with physiologic dose steroids are allowed.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.