Study of Axicabtagene Ciloleucel Given With Steroids In Participants With Relapsed Or Refractory Large B-Cell Lymphoma

Study Overview
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Brief Summary
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The goal of this clinical study is to learn more about the study drug, axicabtagene ciloleucel, in participants with relapsed or refractory large B-cell lymphoma (LBCL) in the outpatient setting.

Detailed Description
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Participants who complete at minimum 24 months follow up will be transitioned to a separate long-term follow-up study (study KT-US-982-5968) to complete the remainder of the 15-year follow-up assessments.

Official Title
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A Phase 2 Open-Label, Multicenter Study Evaluating The Safety And Efficacy of Axicabtagene Ciloleucel Concomitant With Prophylactic Steroids In Subjects With Relapsed Or Refractory Large B-Cell Lymphoma In The Outpatient Setting

Conditions
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Relapsed or Refractory Large B-cell Lymphoma

Intervention / Treatment
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* Biological: Axicabtagene Ciloleucel
* Drug: Cyclophosphamide
* Drug: Fludarabine
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically confirmed large B-cell lymphoma (LBCL), including the following types defined by World Health Organization (WHO) 2016 classification, by local pathology laboratory assessment, are eligible as defined below: Diffuse large B-cell lymphoma (DLBCL) not otherwise specified. High-grade B-cell lymphoma (HGBL) with or without MYC and BCL2 and/or BCL6 rearrangement. DLBCL associated with chronic inflammation; Epstein-Barr virus (EBV) + DLBCL. Primary mediastinal (thymic) LBCL. Primary cutaneous DLBCL, leg type. Transformation of follicular lymphoma to DLBCL will also be included. Relapsed or refractory disease after 1 or more lines of therapy. Individuals must have received adequate prior therapy including: Anti-CD20 monoclonal antibody AND An anthracycline-containing chemotherapy regimen. At least 1 measurable lesion according to the Lugano Response Criteria for Malignant Lymphoma. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Individual agrees to outpatient treatment setting and to adhere to the prespecified clinical monitoring requirements. Key Exclusion Criteria: History of autologous or allogeneic stem cell transplant. Prior cluster of differentiation (CD)19 targeted therapy. Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management. Simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the Kite medical monitor. Individuals with detectable cerebrospinal fluid malignant cells, brain metastases, or with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma. DLBCL epidural involvement should be considered as positive CNS disease. In the investigator's judgment, the individual is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Axicabtagene Ciloleucel<br>Participant will receive lymphodepleting chemotherapy (cyclophosphamide 500 mg/m^2/day and fludarabine 30 mg/m^2/day) over 3 days (Days -5, -4, and -3) followed by prophylactic corticosteroid treatment with 10 mg dexamethasone on Day 0 (prior to axicabtagene ciloleucel), Day 1, and Day 2. Participant will receive axicabtagene ciloleucel consisting of a single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells on Day 0 (following dexamethasone 10 mg) at a target dose of 2 x 10^6 cells/kg. | Biological: Axicabtagene Ciloleucel<br>* Administered intravenously<br>* Other names: Yescarta®;Drug: Cyclophosphamide<br>* Administered intravenously<br>Drug: Fludarabine<br>* Administered intravenously<br>Drug: Dexamethasone<br>* Administered orally or intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage and Severity of Participants with Treatment-emergent Cytokine Release Syndrome (CRS) and Neurologic Events |  | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Onset of CRS and Neurologic Events Following Axicabtagene Ciloleucel Administration |  | First infusion date of axicabtagene ciloleucel up to 24 months | 
| Duration of CRS and Neurologic Events Following Axicabtagene Ciloleucel Administration |  | First infusion date of axicabtagene ciloleucel up to 24 months | 
| Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 72 hours |  | First infusion date of axicabtagene ciloleucel up to 72 hours | 
| Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 7 days |  | First infusion date of axicabtagene ciloleucel up to 7 days | 
| Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 14 days |  | First infusion date of axicabtagene ciloleucel up to 14 days | 
| Rates of Hospitalization After Axicabtagene ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 30 days |  | First infusion date of axicabtagene ciloleucel up to 30 days | 
| Duration of Initial Hospitalization After Axicabtagene Ciloleucel Infusion |  | First infusion date of axicabtagene ciloleucel up to 24 months | 
| Proportion of Intensive Care Unit (ICU) Admitted Participants |  | Up to 24 months | 
| Duration of ICU Admission During First Hospitalization After Axicabtagene Ciloleucel Infusion |  | Up to 24 months | 
| Percentage of Participants Experiencing Treatment- Emergent Adverse Events |  | First infusion date of axicabtagene ciloleucel up to 24 months | 
| Percentage of Participants Experiencing Treatment- Emergent Serious Adverse Events |  | First infusion date of axicabtagene ciloleucel up to 24 months | 
| Change in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) From Baseline to Month 6 | The EQ-5D-5 levels (EQ-5D-5L) is a standardized measure of health status of the participant that provides a simple, generic measure of health for clinical and economic appraisal. EQ-5D-5L consists of 2 components: a descriptive system of the participant's health and a rating of his or her current health state on a 0-100 VAS. The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. 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. | Baseline, 6 Months | 
| Objective Response Rate (ORR) as Assessed by Investigator Assessment | ORR is defined as the incidence of either a complete response or a partial response by the revised international working group (IWG) response criteria for malignant lymphoma. | Up to 24 months | 
| Complete Response (CR) Rate as Assessed by Investigator Assessment | CR rate is defined as the incident of complete response. | Up to 24 months | 
| Duration of response (DOR) as Assessed by Investigator Assessment | DOR is defined as the time from first objective response to disease progression per the revised IWG response criteria for malignant lymphoma or death from any cause. | Up to 24 months | 
| Progression-free Survival (PFS) as Assessed by Investigator Assessment | PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per the revised IWG response criteria for malignant lymphoma or death from any cause. | Up to 24 months | 
| Event Free Survival (EFS) as Assessed by Investigator Assessment | EFS is defined as the time from infusion to the earliest date of disease progression per the revised IWG response criteria for malignant lymphoma, commencement of new anti-lymphoma therapy, or death from any cause. | Up to 24 months | 
| Overall Survival (OS) | OS is defined as the time from axicabtagene ciloleucel infusion to the date of death. | Up to 24 months | 
| Peak Serum Levels of Homeostatic/Proliferative Cytokines: Interleukin (IL)-2, IL-7, and IL-15 |  | Up to 24 months | 
| Peak Serum Levels of Inflammatory and Immune Modulating Cytokines: IFN-γ, IL-1, IL-6, IL- 13, IL-17, IL-1, IL-1RA, Granulocyte-macrophage Colony Stimulating Factor (GM-CSF), Tumor Necrosis Factor-Alpha (TNF-α), and IL-12p40/p70 | IFN-γ=Interferon-Gamma, IL-1RA=IL-1 Receptor Antagonist | Up to 24 months | 
| Peak Serum Levels of Immune Effector Molecules: Granzyme A, Granzyme B, and Perforin |  | Up to 24 months | 
| Peak Serum Levels of the Acute Phase Response Proteins: C-Reactive Protein (CRP), Serum Amyloid A (SAA), Soluble IL-2 Receptor Alpha (sIL-1Ra), Ferritin |  | Up to 24 months | 
| Peak Serum Levels of Chemokines: IL-8, C-X-C Motif Chemokine Ligand-10 (CXCL-10), and Monocyte Chemotactic Protein-1 (MCP-1). |  | Up to 24 months | 
| Blood Levels of Axicabtagene Ciloleucel Chimeric Antigen Receptor (CAR) T-cells Over Time |  | Up to 24 months |