Clinical Trials /

Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Participants With High-Risk Large B-Cell Lymphoma

NCT03761056

Description:

The primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in participants with high-risk large B-cell lymphoma.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Participants With High-Risk Large B-Cell Lymphoma
  • Official Title: A Phase 2 Multicenter Study Evaluating the Efficacy and Safety of Axicabtagene Ciloleucel as First-Line Therapy in Subjects With High-Risk Large B-Cell Lymphoma (ZUMA-12)

Clinical Trial IDs

  • ORG STUDY ID: KTE-C19-112
  • NCT ID: NCT03761056

Conditions

  • B-cell Lymphoma

Interventions

DrugSynonymsArms
Axicabtagene CiloleucelYescarta®Axicabtagene Ciloleucel
FludarabineAxicabtagene Ciloleucel
CyclophosphamideAxicabtagene Ciloleucel

Purpose

The primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in participants with high-risk large B-cell lymphoma.

Trial Arms

NameTypeDescriptionInterventions
Axicabtagene CiloleucelExperimentalParticipants will receive cyclophosphamide and fludarabine conditioning chemotherapy followed by the investigational treatment, axicabtagene ciloleucel
  • Axicabtagene Ciloleucel
  • Fludarabine
  • Cyclophosphamide

Eligibility Criteria

        Key Inclusion Criteria:

          -  Histologically confirmed large B-cell lymphoma

          -  High-grade large B-cell lymphoma

          -  Individuals must have a positive interim positron emission tomography (PET) per
             Cheson, 2014 (Deauville PET score of 4 or 5) after 2 cycles (PET2+) of
             chemoimmunotherapy

          -  No evidence, suspicion and/or history of CNS involvement of lymphoma

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Absolute neutrophil count ≥ 1000/μL

          -  Platelet count ≥ 75,000/μL

          -  Absolute lymphocyte count ≥ 100/μL

          -  Adequate renal, hepatic, pulmonary, and cardiac function defined as:

               -  Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min

               -  Serum alanine aminotransferase (ALT/AST) ≤ 2.5 upper limit of normal (ULN)

               -  Total bilirubin ≤1.5 mg/dL, except in individuals with Gilbert's syndrome

          -  Cardiac ejection fraction ≥ 50% , no evidence of pericardial effusion as determined by
             an ECHO, and no clinically significant ECG findings

          -  No clinically significant pleural effusion

          -  Baseline oxygen saturation > 92% on room air

        Key Exclusion Criteria:

          -  History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg
             cervix, bladder, breast) unless disease free for at least 3 years

          -  History of Richter's transformation of chronic lymphocytic leukemia or primary
             mediastinal B-cell lymphoma

          -  History of autologous or allogeneic stem cell transplant

          -  Prior CD19-targeted therapy

          -  Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy

          -  Presence or suspicion of fungal, bacterial, viral, or other infection that is
             uncontrolled or requiring IV antimicrobials for management

          -  History of HIV infection or acute or chronic active hepatitis B or C infection

          -  Presence of any indwelling line or drain dedicated central venous access catheters,
             such as a Port-a-Cath or Hickman catheter, are permitted

          -  Individuals with detectable cerebrospinal fluid malignant cells, brain metastases, or
             active CNS lymphoma

          -  History or presence of CNS disorder, such as seizure disorder, cerebrovascular
             ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS
             involvement

          -  History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or
             other clinically significant cardiac disease within 12 months of enrollment

          -  History of autoimmune disease resulting in end organ injury or requiring systemic
             immunosuppression/systemic disease modifying agents within the last 2 years

          -  History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of
             enrollment

        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:Complete Response rate is defined as the incidence of a CR per the Lugano Classification as determined by study investigators.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Up to 15 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 15 years
Safety Issue:
Description:DOR is defined only for participants who experience an objective response after axicabtagene ciloleucel infusion and is the time from the first objective response to disease progression or death from any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Kite, A Gilead Company

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