Clinical Trials /

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

NCT04002401

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: KT-US-471-0114
  • NCT ID: NCT04002401

Conditions

  • Refractory Large B-cell Lymphoma

Interventions

DrugSynonymsArms
Axicabtagene CiloleucelYescarta®Axicabtagene Ciloleucel and Rituximab Combination
RituximabRITUXAN®Axicabtagene Ciloleucel and Rituximab Combination
LenalidomideREVLIMID®Axicabtagene Ciloleucel and Lenalidomide Combination
FludarabineAxicabtagene Ciloleucel and Rituximab Combination
CyclophosphamideAxicabtagene Ciloleucel and Rituximab Combination

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Axicabtagene Ciloleucel and Rituximab CombinationExperimentalParticipants will receive rituximab, and fludarabine and cyclophosphamide conditioning chemotherapy, followed by axicabtagene ciloleucel and additional rituximab.
  • Axicabtagene Ciloleucel
  • Rituximab
  • Fludarabine
  • Cyclophosphamide
Axicabtagene Ciloleucel and Lenalidomide CombinationExperimentalParticipants will receive lenalidomide, and fludarabine and cyclophosphamide conditioning chemotherapy, followed by axicabtagene ciloleucel and additional lenalidomide.
  • Axicabtagene Ciloleucel
  • Lenalidomide
  • Fludarabine
  • Cyclophosphamide

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 bone marrow, renal, hepatic, pulmonary, and cardiac function

          -  Individuals must be able to comply with the requirements of REVLIMID Risk Evaluation
             and Mitigation Strategy (REMS)®

        Key Exclusion Criteria:

          -  Known CD19 negative or CD20 negative tumor

          -  History of Richter's transformation of Chronic Lymphocytic Leukemia (CLL)

          -  Prior lenalidomide or other immunomodulatory imide drug (IMiD) treatment

          -  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 year

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Gilead Sciences

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