Clinical Trials /

A Study Evaluating KTE-X19 in Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ZUMA-3)

NCT02614066

Description:

The primary objectives of this study are to determine the safety and efficacy of KTE-X19 adult 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 Study Evaluating KTE-C19 in Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL) (ZUMA-3)
  • Official Title: A Phase 1-2 Multi-Center Study Evaluating the Safety and Efficacy of KTE-C19 in Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL) (ZUMA-3)

Clinical Trial IDs

  • ORG STUDY ID: KTE-C19-103
  • NCT ID: NCT02614066

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).

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
    
                   -  First relapse if first remission ≤ 12 months
    
                   -  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. Age 18 or older
    
              5. Eastern cooperative oncology group (ECOG) performance status of 0 or 1
    
              6. Adequate renal, hepatic, pulmonary and cardiac function defined as:
    
                   -  Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 cc/min
    
                   -  Serum ALT/AST ≤ 2.5 x ULN
    
                   -  Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert's syndrome.
    
                   -  Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion, and no
                      clinically significant arrhythmias
    
                   -  Baseline oxygen saturation > 92% on room air
    
              7. In subjects previously treated with blinatumomab, CD19 tumor expression in bone marrow
                 or peripheral blood.
    
            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. Isolated extramedullary disease
    
              4. CNS abnormalities
    
                   -  Presence of CNS-3 disease or CNS-2 disease with neurological changes
    
                   -  History or presence of any CNS disorder such as a seizure disorder,
                      cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any
                      autoimmune disease with CNS involvement
    
              5. History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome,
                 Shwachman-Diamond syndrome or any other known bone marrow failure syndrome
    
              6. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or
                 other clinically significant cardiac disease within 12 months of enrollment
    
              7. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of
                 enrollment.
    
              8. Primary immunodeficiency
    
              9. Known infection with HIV, hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV
                 positive).
    
             10. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or
                 requiring IV antimicrobials for management.
    
             11. Prior medication:
    
                   -  Salvage chemotherapy including TKIs for Ph+ ALL within 1 week prior to enrollment
    
                   -  Prior CD19 directed therapy other than blinatumomab
    
                   -  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
    
                   -  At least 3 half-lives must have elapsed from any prior systemic
                      inhibitory/stimulatory immune checkpoint molecule therapy prior to enrollment
    
                   -  Corticosteroid therapy for 7 days prior to enrollment
    
             12. Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube,
                 indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter).
                 Ommaya reservoirs and dedicated central venous access catheters such as a Port-a-Cath
                 or Hickman catheter are permitted
    
             13. 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
    
             14. Live vaccine ≤ 4 weeks prior to enrollment
    
             15. 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 or who have been postmenopausal for
                 at least 2 years are not considered to be of childbearing potential
    
             16. 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
    
             17. In the investigators judgment, the subject is unlikely to complete all
                 protocol-required study visits or procedures, including follow-up visits, or comply
                 with the study requirements for participation
    
             18. History of autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus)
                 resulting in end organ injury or requiring systemic immunosuppression/systemic disease
                 modifying agents within the last 2 years
          
    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:

    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