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Trial record 1 of 1 for:    NCT02625480
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Study Evaluating KTE-C19 in Pediatric and Adolescent Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ZUMA-4)

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ClinicalTrials.gov Identifier: NCT02625480
Recruitment Status : Recruiting
First Posted : December 9, 2015
Last Update Posted : May 7, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences ( Kite, A Gilead Company )

Tracking Information
First Submitted Date  ICMJE December 5, 2015
First Posted Date  ICMJE December 9, 2015
Last Update Posted Date May 7, 2019
Actual Study Start Date  ICMJE February 1, 2016
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
  • Phase 1: Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities (DLT) [ Time Frame: Up to 28 days ]
    Dose-limiting toxicity is defined as protocol-defined KTE-C19-related events with onset within the first 28 days following KTE-C19 infusion.
  • Phase 2: Overall Complete Remission Rate [ Time Frame: Up to 24 months ]
    Overall complete remission rate will be determined per independent review.
Original Primary Outcome Measures  ICMJE
 (submitted: December 8, 2015)
  • Phase 1: Safety (Incidence of adverse events defined as dose-limiting toxicities (DLT) [ Time Frame: 30 Days ]
  • Phase 2: Overall Complete Remission Rate [ Time Frame: 8 weeks ]
Change History Complete list of historical versions of study NCT02625480 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
  • Duration of Remission [ Time Frame: Up to 24 months ]
    Duration of remission is defined as the time between the participant's first complete response per independent review to relapse or any death in the absence of documented relapse.
  • Minimum Residual Disease Negative Remission Rate [ Time Frame: Up to 3 months ]
    Minimal residual disease (MRD) response rate is defined as MRD < 10^-4 per the standard assessment.
  • Allogeneic Stem Cell Transplant Rate [ Time Frame: Up to 24 months ]
    The incidence of allogeneic stem cell transplant will be analyzed.
  • Overall Survival [ Time Frame: Up to 15 years ]
    Overall survival is defined as the time from KTE-C19 infusion to the date of death from any cause.
  • Relapse-Free Survival [ Time Frame: Up to 24 months ]
    Relapse-Free Survival is defined as the time from the KTE-C19 infusion date to the date of disease relapse or death from any cause.
  • Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: Up to 15 years ]
  • Percentage of Participants Experiencing Common Terminology Criteria for Adverse Events (CTCAE) Grade Changes in Safety Laboratory Values [ Time Frame: Up to 15 years ]
  • Percentage of Participants with Anti-KTE-C19 Antibodies [ Time Frame: Up to 15 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 8, 2015)
  • Duration of Remission [ Time Frame: 12 Months ]
  • Minimum Residual Disease Negative Remission Rate [ Time Frame: 8 Weeks ]
  • Allogeneic Stem Cell Transplant Rate [ Time Frame: 12 Months ]
  • Overall Survival [ Time Frame: 12 Months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Evaluating KTE-C19 in Pediatric and Adolescent Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
Official Title  ICMJE 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 (ZUMA-4)
Brief Summary 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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Lymphoblastic Leukemia
Intervention  ICMJE
  • Biological: KTE-C19
  • Drug: Fludarabine
    Administered intravenously
  • Drug: Cyclophosphamide
    Administered intravenously
Study Arms  ICMJE Experimental: Single Arm
A 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 or 1 x 10^6 anti-CD19 CAR+ T cells/kg
Interventions:
  • Biological: KTE-C19
  • Drug: Fludarabine
  • Drug: Cyclophosphamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 1, 2018)
100
Original Estimated Enrollment  ICMJE
 (submitted: December 8, 2015)
75
Estimated Study Completion Date  ICMJE January 2036
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Relapsed or refractory B-precursor ALL defined as one of the following:

    • Primary refractory disease
    • Relapsed or refractory disease after 2 or more lines of systemic therapy
    • Relapsed or refractory disease after allogeneic transplant provided individual is at least 100 days from stem cell transplant at the time of enrollment
  • Morphological disease in the bone marrow (> 5% blasts)
  • Individuals 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
  • Ages 2 to 21 at the time of Assent or Consent per institutional review board (IRB) guidelines
  • 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
  • Adequate renal, hepatic, pulmonary and cardiac function defined as:

    • Creatinine clearance ≥ 60 cc/min
    • Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 5 x upper limit of normal (ULN)
    • Total bilirubin ≤ 1.5 x ULN, except in individuals with Gilbert's syndrome
    • Left ventricular shortening fraction (LVSF) ≥ 30% or left ventricular ejection fraction (LVEF) ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram, and no clinical significant arrhythmias
    • No clinically significant pleural effusion
    • Baseline oxygen saturation > 92% on room air

Key Exclusion Criteria

  • Diagnosis of Burkitt's leukemia/lymphoma according to the World Health Organization (WHO) classification or chronic myelogenous leukemia lymphoid blast crisis
  • 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
  • History of severe hypersensitivity reaction to aminoglycosides or any of the agents used in this study
  • Presence of central nervous system (CNS)-3 disease and CNS-2 disease with neurological changes
  • History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome or any other known bone marrow failure syndrome
  • History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
  • History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment.
  • Primary immunodeficiency
  • Known infection with HIV, hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive)
  • Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.
  • Prior medication:

    • Prior CD19 directed therapy, including CAR+ T cell, BiTE, and antibody drug conjugate (ADC), with the exception of individuals 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 graft-versus-host disease (GVHD) within 4 weeks prior to enrollment
  • 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
  • Live vaccine ≤ 6 weeks prior to start of conditioning regimen
  • 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
  • Individuals 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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Medical Information 1-844-454-5483(1-844-454-KITE) medinfo@kitepharma.com
Listed Location Countries  ICMJE Canada,   France,   Netherlands,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02625480
Other Study ID Numbers  ICMJE KTE-C19-104
2015-005010-30 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gilead Sciences ( Kite, A Gilead Company )
Study Sponsor  ICMJE Kite, A Gilead Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Kite Study Director Kite, A Gilead Company
PRS Account Gilead Sciences
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP