High-risk Large B-cell Lymphoma (LBCL)
Conditions
Brief summary
The goal of this clinical study is to compare the study drug, axicabtagene ciloleucel, versus standard of care (SOC) in first-line therapy in participants with high-risk large B-cell lymphoma.
Detailed description
Five years after randomization, participants who have received axicabtagene ciloleucel will transition to a separate long-term follow-up study (study KT-US-982-5968) to complete the remainder of the 15-year follow-up assessments.
Interventions
BIOLOGICALAxicabtagene Ciloleucel
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells
DRUGCyclophosphamide
Administered intravenously
DRUGFludarabine
Administered intravenously
DRUGEtoposide
Administered intravenously
DRUGRituximab
Administered intravenously
DRUGDoxorubicin
Administered intravenously
DRUGVincristine
Administered intravenously
DRUGPrednisone
Administered orally
Sponsors
Kite, A Gilead Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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) * 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. * Have received only 1 cycle of rituximab plus chemotherapy (R-chemotherapy). * Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function. * Females of childbearing potential must have a negative serum or urine pregnancy test. 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 * History of Richter's transformation of chronic lymphocytic leukemia * Presence of detectable cerebrospinal fluid (CSF)-malignant cells, brain metastases, or a history of CNS involvement of lymphoma. * Presence of cardiac 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. * Presence of CNS disorder. 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. * 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 or residual toxicities from prior therapies likely to interfere with assessment of safety or efficacy of study treatment. Please refer to protocol for further details. * History of clinically significant cardiac disease within 12 months before enrollment. * History of any medical condition requiring maintenance systemic immunosuppression/systemic disease modifying agents within the last 2 years. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free Survival (EFS) by Blinded Central Assessment | Up to 5 years | EFS, is defined as the time from randomization to the earliest occurrence of death due to any cause, disease progression/relapse, initiation of any non-protocol specified subsequent new lymphoma therapy for the treatment of residual disease or Biopsy-proven residual disease at the Month 6 disease assessment or later, regardless of whether subsequent new lymphoma therapy is initiated or not. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) by Blinded Central Assessment | Up to 5 years | PFS is defined as the time from randomization to disease progression or death due to any cause. |
| Overall Survival | Up to 5 years | OS is defined as the time from randomization to death due to any cause. |
| PFS by Investigator Assessment | Up to 5 years | PFS is defined as the time from randomization to disease progression or death due to any cause. |
| Complete Response (CR) Rate by Blinded Central Assessment | Up to 5 years | CR rate is defined as the proportion of participants who have achieved CR per Lugano classification after treatment completion and prior to subsequent new off protocol anti-lymphoma therapy. |
| Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Deaths | First dose date up to 5 years plus 30 days | — |
| Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values | First dose date up to 5 years plus 30 days | — |
| Change From Baseline in the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-30 (EORTC QLQ-C30) Score | Baseline, Month 18 | The EORTC-QLQ-C30 is a multi-item questionnaire measuring the following content: five (5) multi-item functional scales, three (3) multi-item symptom scales, six (6) symptom single-item scales, one (1) global health status scale, and one (1) global health-related quality of life (HRQoL). Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functioning scales and for the Global Health Status or Global HRQoL scales indicate a higher level of functioning and a better HRQoL respectively, whereas higher scores in symptom scales represent a higher level of symptoms. |
| Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Non-Hodgkin Lymphoma High Grade Module (EORTC QLQ-NHL-HG29) Score | Baseline, Month 18 | The EORTC QLQ-NHL-HG29 is a 29-item patient-reported assessment measuring patients' high-grade NHL-specific symptoms and functioning. The 29 items assess symptom burden due to disease and/or treatment, fatigue/physical condition, neuropathy, emotional impacts, and worries/fears health and functioning. Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functional scales indicate a higher level of functioning and a better HRQoL, whereas higher scores in symptom scales represent a higher level of symptoms. |
| Change From Baseline in the European Quality of Life Five Dimensions Five Levels Questionnaire (EQ-5D-5L) Score | Baseline, Month 18 | The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L comprises 2 components: a questionnaire covering 5 dimensions and a tariff of values based upon direct valuations of health states using a visual analog scale (VAS). Rating gets recorded on a vertical VAS in which the endpoints are labeled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ VAS indicate better health. |
Countries
Australia, Austria, Canada, France, Germany, Italy, Japan, Netherlands, Portugal, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORKite Study Director
Kite, A Gilead Company
Outcome results
None listed