A Multi-Center Study Evaluating KTE-C19 in Pediatric and Adolescent Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ZUMA-4)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02625480
Recruitment Status : Recruiting
First Posted : December 9, 2015
Last Update Posted : April 6, 2018
Information provided by (Responsible Party):
Kite, A Gilead Company

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Biological: KTE-C19 Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Study Start Date : December 2015
Estimated Primary Completion Date : June 2019

Arm Intervention/treatment
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
Biological: KTE-C19

Primary Outcome Measures :
  1. Phase 1: Safety (Incidence of adverse events defined as dose-limiting toxicities (DLT) [ Time Frame: 30 Days ]
  2. Phase 2: Overall complete remission rate [ Time Frame: 8 weeks ]

Secondary Outcome Measures :
  1. Duration of Remission [ Time Frame: 12 Months ]
  2. Minimum Residual Disease Negative Remission Rate [ Time Frame: 8 Weeks ]
  3. Allogeneic Stem Cell Transplant Rate [ Time Frame: 12 Months ]
  4. Overall Survival [ Time Frame: 12 Months ]

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Ages Eligible for Study:   2 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02625480

Contact: Medical Information 844-454-KITE

United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Adria Arencibia   
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Cathy Salata    323-361-2480   
Children's Hospital of Orange County Recruiting
Orange, California, United States, 92868
Contact: Laura Gates   
Contact: Dorian Chan    714-509-7868   
UCSF Benioff Childrens Hospital Recruiting
San Francisco, California, United States, 94158
Contact: Anna Garzon    415-476-3982   
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Debra Schissel    720-777-2879   
United States, Florida
Sylvester Comprehensive Cancer Center/UMHC Recruiting
Miami, Florida, United States, 33136
Contact: Michelle Liendo    305-243-0850   
Principal Investigator: Edward Ziga, MD         
United States, Illinois
Ann & Robert H. Lurie Children's Hospital Recruiting
Chicago, Illinois, United States, 60611
Contact: Knute Martell   
Contact: Yolanda Santiago   
University of Chicago Recruiting
Chicago, Illinois, United States
Contact: Jacqueline Ansted    773-702-1191   
United States, Maryland
Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21287
Contact: Pat Rice   
Contact: Genevieve Courpas   
United States, Minnesota
Children's Hospitals and Clinics of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55404
Contact: Ana Brown   
Contact: Jennifer Lee   
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Jeanne Hanson    507-284-2657   
Contact: Debra Schott   
United States, Ohio
Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States
Contact: Courtney Blank    513-803-3255   
Contact: Lori Backus    513-636-2047   
United States, Pennsylvania
The Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Vikram Shenoy   
Principal Investigator: Stephan Grupp, MD, PhD         
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37232
Contact: Gina Perez   
Contact: Amanda Stults   
Vanderbilt University Recruiting
Nashville, Tennessee, United States
Contact: Gina Perez   
United States, Texas
The University of Texas M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030-4009
Contact: Krystal Bolton   
Principal Investigator: Michael Rytting, MD         
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Helton Cruz   
United States, Virginia
University of Virginia Health System Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Allison Watkins    434-924-0370   
Principal Investigator: Daniel Lee, MD         
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Adam Fielbelkorn   
Canada, Ontario
The Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G1X8
Contact: Abongnwen Abianui   
Principal Investigator: Joerg Krueger, MD         
Sponsors and Collaborators
Kite, A Gilead Company
Study Director: Rajul Jain, M.D. Kite, A Gilead Company

Responsible Party: Kite, A Gilead Company Identifier: NCT02625480     History of Changes
Other Study ID Numbers: KTE-C19-104
First Posted: December 9, 2015    Key Record Dates
Last Update Posted: April 6, 2018
Last Verified: April 2018

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases