Clinical Trials /

Study Evaluating KTE-C19 in Pediatric and Adolescent Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia

NCT02625480

Description:

The primary objectives of this study are to evaluate the safety and efficacy of KTE-C19 in pediatric and adolescent participants with relapsed/refractory (r/r) B-precursor acute lymphoblastic leukemia (ALL).

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Multi-Center Study Evaluating KTE-C19 in Pediatric and Adolescent Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
  • Official Title: A Phase 1-2 Multi-Center Study Evaluating the Safety and Efficacy of KTE C19 in Pediatric and Adolescent Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL) (ZUMA-4)

Clinical Trial IDs

  • ORG STUDY ID: KTE-C19-104
  • NCT ID: NCT02625480

Conditions

  • Acute Lymphoblastic Leukemia

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 relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL) in pediatric or adolescent subjects.

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

            Inclusion Criteria:
    
              1. Relapsed or refractory B-precursor ALL defined as one of the following:
    
                   -  Primary refractory disease
    
                   -  Relapsed or refractory disease after first or later salvage therapy
    
                   -  Relapsed or refractory disease after allogeneic transplant provided subject is at
                      least 100 days from stem cell transplant at the time of enrollment
    
              2. Morphological disease in the bone marrow (≥ 5% blasts)
    
              3. Subjects with Ph+ disease are eligible if they are intolerant to tyrosine kinase
                 inhibitor (TKI) therapy, or if they have relapsed/refractory disease despite treatment
                 with at least 2 different TKIs
    
              4. Ages 2 to 21 at the time of Assent or Consent per IRB guidelines
    
              5. Lansky (age < 16 years at the time of assent/consent) or Karnofsky (age ≥ 16 years at
                 the time of assent/consent) performance status ≥ 80 at screening
    
              6. Adequate renal, hepatic, pulmonary and cardiac function defined as:
    
                   -  Creatinine clearance ≥ 60 cc/min
    
                   -  Serum ALT/AST ≤ 2.5 x ULN
    
                   -  Total bilirubin ≤ 1.5 x ULN
    
                   -  Cardiac ejection fraction ≥ 50% and no clinically significant ECG findings
    
                   -  Baseline oxygen saturation > 92% on room air
    
            Exclusion Criteria
    
              1. Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic
                 myelogenous leukemia lymphoid blast crisis
    
              2. History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g.
                 cervix, bladder, breast) unless disease free for at least 3 years
    
              3. Presence of CNS-3 disease and CNS-2 disease with neurological changes
    
              4. History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome,
                 Shwachman-Diamond syndrome or any other known bone marrow failure syndrome
    
              5. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or
                 other clinically significant cardiac disease within 12 months of enrollment
    
              6. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of
                 enrollment.
    
              7. Primary immunodeficiency
    
              8. Known infection with HIV, hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV
                 positive)
    
              9. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or
                 requiring IV antimicrobials for management.
    
             10. Prior medication:
    
                   -  Prior CD19 directed therapy, including CAR+ T cell, BiTE, and antibody drug
                      conjugate (ADC), with the exception of subjects who received KTE-C19 in this
                      study and are eligible for re-treatment
    
                   -  Treatment with alemtuzumab within 6 months prior to leukapheresis, or treatment
                      with clofarabine or cladribine within 3 months prior to leukapheresis
    
                   -  Donor lymphocyte infusion (DLI) within 28 days prior to enrollment
    
                   -  Any drug used for GVHD within 4 weeks prior to enrollment
    
             11. Acute GVHD grade II-IV by Glucksberg criteria or severity B-D by IBMTR index; acute or
                 chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment
    
             12. Live vaccine ≤ 6 weeks prior to start of conditioning regimen
    
             13. Women of child-bearing potential who are pregnant or breastfeeding because of the
                 potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
                 Females who have undergone surgical sterilization are not considered to be of
                 childbearing potential
    
             14. Subjects of both genders of child-bearing potential who are not willing to practice
                 birth control from the time of consent through 6 months after the completion of
                 KTE-C19
          
    Maximum Eligible Age:21 Years
    Minimum Eligible Age:2 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:

    Secondary Outcome Measures

    Measure:Duration of Remission
    Time Frame:12 Months
    Safety Issue:
    Description:
    Measure:Minimum Residual Disease Negative Remission Rate
    Time Frame:8 Weeks
    Safety Issue:
    Description:
    Measure:Allogeneic Stem Cell Transplant Rate
    Time Frame:12 Months
    Safety Issue:
    Description:
    Measure:Overall Survival
    Time Frame:12 Months
    Safety Issue:
    Description:

    Details

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

    Last Updated

    July 25, 2017