Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in combination with rituximab, as measured by assessment of response rates in adult participants with relapsed/refractory large B-cell lymphoma.

Detailed Description
-----------------
Following at least 24 months of assessments after axicabtagene ciloleucel infusion, participants will be asked to rollover to a separate long-term follow-up study (Study KT-US-982-5968). Participants will complete the remainder of the 15-year follow-up assessments in the KT-US-982-5968 study.

Official Title
-----------------
A Phase 2 Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma (ZUMA-14)

Conditions
-----------------
Refractory Large B-cell Lymphoma

Intervention / Treatment
-----------------
* Biological: Axicabtagene Ciloleucel
* Drug: Rituximab
* Drug: Fludarabine
* Drug: Cyclophosphamide


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Histologically confirmed large B-cell lymphoma Chemotherapy-refractory disease, defined as one or more of the following: No response to first-line therapy (primary refractory disease) No response to second or greater lines of therapy OR Refractory after autologous stem cell transplant (ASCT) At least 1 measureable lesion according to the Lugano Classification (Cheson 2014). Individuals must have received adequate prior therapy, including at a minimum: Anti-CD20 monoclonal antibody An anthracycline-containing chemotherapy regimen Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate renal, hepatic, pulmonary, and cardiac function Key Exclusion Criteria: Known CD19 negative or CD20 negative tumor History of Richter's transformation of Chronic Lymphocytic Leukemia (CLL) Prior CAR therapy or other genetically modified T-cell therapy Prior organ transplantation including prior allogeneic stem cell transplant (SCT) Prior CD19 targeted therapy Clinically significant infection or cardiopulmonary disease Presence of any in-dwelling lines or drains (dedicated central venous access catheters allowed) History or presence of central nervous system (CNS) lymphoma or nonmalignant CNS disorder or cerebrospinal fluid (CSF) malignant cells or brain metastases History of autoimmune disease History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the last 6 months Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 and Rituximab Combination<br>Participants will receive rituximab, and fludarabine and cyclophosphamide conditioning chemotherapy, followed by axicabtagene ciloleucel and additional rituximab. | Biological: Axicabtagene Ciloleucel<br>* A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously<br>* Other names: Yescarta®;Drug: Rituximab<br>* Administered intravenously<br>* Other names: RITUXAN®;Drug: Fludarabine<br>* Administered according to package insert<br>Drug: Cyclophosphamide<br>* Administered according to package insert<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response (CR) Rate | CR rate is defined as the incidence of a CR per the Lugano Classification as determined by study investigators. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Experiencing Adverse Events and Clinically Significant Changes in Safety Lab Values |  | Up to 15 years | 
| Objective Response Rate (ORR) | ORR is defined as the incidence of either a CR or a partial response (PR) per the Lugano Classification as determined by study investigators. | Time Frame: Up to 2 years | 
| Duration of Response (DOR) | DOR is defined only for participants who experience an objective response and is the time from the first objective response to disease progression per the Lugano Classification as determined by study investigators or death from any cause. | Up to 2 years | 
| Progression-Free Survival (PFS) | PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per Lugano Classification as determined by study investigators or death from any cause. | Up to 2 years | 
| Overall Survival (OS) | OS is defined as the time from axicabtagene ciloleucel infusion to the date of death. | Up to 15 years | 
| Levels of Axicabtagene Ciloleucel in Blood |  | Up to 2 years |