Clinical Trials /

Safety and Efficacy of KTE-C19 in Adults With Refractory Aggressive Non-Hodgkin Lymphoma

NCT02348216

Description:

This study will be separated into 3 distinct phases designated as the Phase 1 study, Phase 2 pivotal study (Cohort 1 and Cohort 2), and Phase 2 safety management study (Cohort 3 and Cohort 4, Cohort 5 and Cohort 6). The primary objectives of this study are: - Phase 1 Study: Evaluate the safety of axicabtagene ciloleucel regimens - Phase 2 Pivotal Study; Evaluate the efficacy of axicabtagene ciloleucel - Phase 2 Safety Management Study: Assess the impact of prophylactic regimens or earlier interventions on the rate and severity of cytokine release syndrome (CRS) and neurologic toxicities

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

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1-2 Multi-Center Study Evaluating KTE-C19 in Subjects With Refractory Aggressive Non-Hodgkin Lymphoma (ZUMA-1)
  • Official Title: A Phase 1-2 Multi-Center Study Evaluating the Safety and Efficacy of KTE-C19 in Subjects With Refractory Aggressive Non-Hodgkin Lymphoma (NHL)

Clinical Trial IDs

  • ORG STUDY ID: KTE-C19-101
  • NCT ID: NCT02348216

Conditions

  • Refractory Diffuse Large B Cell Lymphoma
  • Refractory Primary Mediastinal B Cell Lymphoma
  • Refractory Transformed Follicular Lymphoma
  • Relapsed/Refractory Transplant Ineligible Diffuse Large B Cell Lymphoma
  • Relapsed/Refractory Transplant Ineligible Primary Mediastinal B Cell Lymphoma
  • Relapsed/Refractory Transplant Ineligible Transformed Follicular Lymphoma

Interventions

DrugSynonymsArms
KTE-C19Single Arm

Purpose

This is a single arm, open-label, multi-center, phase 1/2 study, to determine the safety and efficacy of KTE-C19, an autologous anti-CD19 chimeric antigen receptor (CAR)-positive T cell therapy, in refractory aggressive Non-Hodgkin Lymphoma (NHL).

Trial Arms

NameTypeDescriptionInterventions
Single ArmExperimentalA conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously at a target dose of 2 x 10^6 anti-CD19 CAR+ T cells/kg

    Eligibility Criteria

            Key Inclusion Criteria
    
              1. Histologically confirmed:
    
                   -  Diffuse Large B Cell Lymphoma (DLBCL)
    
                   -  Primary Mediastinal Large B Cell Lymphoma (PMBCL)
    
                   -  Transformation Follicular Lymphoma (TFL)
    
              2. Chemotherapy-refractory disease, defined as one of more of the following:
    
                   -  No response to last line of therapy i. PD as best response to most recent therapy
                      regimen ii. SD as best response to most recent therapy with duration no longer
                      than 6 month from last dose of therapy OR
    
                   -  Refractory post-ASCT i. Disease progression or relapsed less than or equal to 12
                      months of ASCT (must have biopsy proven recurrence in relapsed subjects) ii. If
                      salvage therapy is given post-ASCT, the subject must have had no response to or
                      relapsed after the last line of therapy
    
              3. Subjects must have received adequate prior therapy including at a minimum:
    
                   -  anti-CD20 monoclonal antibody unless investigator determines that tumor is
                      CD20-negative and
    
                   -  an anthracycline containing chemotherapy regimen
    
                   -  for subjects with transformed FL must have received prior chemotherapy for
                      follicular lymphoma and subsequently have chemorefractory disease after
                      transformation to DLBCL
    
              4. At least one measurable lesion per revised IWG Response Criteria
    
              5. Age 18 or older
    
              6. Eastern cooperative oncology group (ECOG) performance status of 0 or 1
    
              7. ANC ≥ 1000/uL
    
              8. ALC >100/uL
    
              9. Platelet count ≥ 75,000/uL
    
             10. Adequate renal, hepatic, pulmonary and cardiac function defined as:
    
                   -  Creatinine clearance (as estimated by Cockcroft Gault) > 60 mL/min
    
                   -  Serum ALT/AST <2.5 ULN
    
                   -  Total bilirubin <1.5 mg/dl, except in subjects with Gilbert's syndrome
    
                   -  Cardiac ejection fraction >50%, no evidence of pericardial effusion as determined
                      by an ECHO, and no clinically significant pleural effusion
    
                   -  Baseline oxygen saturation >92% on room air
    
             11. All subjects or legally appointed representatives/caregivers, must personally sign and
                 date the IRB/IEC approved consent form before initiating any study specific procedures
                 or activities.
    
            Key Exclusion Criteria
    
              1. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g.
                 cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3
                 years
    
              2. History of allogeneic stem cell transplantation
    
              3. Prior CAR therapy or other genetically modified T cell therapy
    
              4. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or
                 requiring IV antimicrobials for management. Simple UTI and uncomplicated bacterial
                 pharyngitis are permitted if responding to active treatment
    
              5. Known history of infection with HIV or hepatitis B (HBsAG positive) or hepatitis C
                 virus (anti-HCV positive). A history of hepatitis B or hepatitis C is permitted if the
                 viral load is undetectable per quantitative PCR and/or nucleic acid testing
    
              6. Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or
                 with a history of CNS lymphoma, cerebrospinal fluid malignant cells or brain
                 metastases
    
              7. History or presence of CNS disorder such as seizure disorder, cerebrovascular
                 ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS
                 involvement
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Phase 1: Safety (Incidence of adverse events defined as dose-limiting toxicities (DLT)
    Time Frame:30 Days
    Safety Issue:
    Description:Incidence of adverse events defined as dose-limiting toxicities (DLT)

    Secondary Outcome Measures

    Measure:Duration of Response
    Time Frame:12 Months
    Safety Issue:
    Description:
    Measure:Progression Free Survival
    Time Frame:12 Months
    Safety Issue:
    Description:
    Measure:Overall Survival
    Time Frame:12 Months
    Safety Issue:
    Description:
    Measure:Safety
    Time Frame:12 Months
    Safety Issue:
    Description:Incidence of adverse events and clinically significant changes in safety lab values, including subgroup analyses

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Kite Pharma, Inc.

    Last Updated

    September 11, 2017