A Study Evaluating KTE-C19 in Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ZUMA-3) (ZUMA-3)

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: NCT02614066
Recruitment Status : Recruiting
First Posted : November 25, 2015
Last Update Posted : October 4, 2018
Information provided by (Responsible Party):
Kite, A Gilead Company

Brief Summary:
The primary objectives of this study are to determine the safety and efficacy of KTE-C19 adult participants with relapsed/refractory (r/r) B-precursor acute lymphoblastic leukemia (ALL).

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 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 Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL) (ZUMA-3)
Actual Study Start Date : March 7, 2016
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : March 2034

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 or 1 x 10^6 anti-CD19 CAR+ T cells/kg
Biological: KTE-C19
Drug: Cyclophosphamide
Administered intravenously

Drug: Fludarabine
Administered intravenously

Primary Outcome Measures :
  1. Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) [ 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.

  2. Phase 2: Overall complete remission rate [ Time Frame: Up to 24 months ]
    (CR + CRi)

Secondary Outcome Measures :
  1. Duration of Remission [ Time Frame: 24 months ]
    Duration of Remission is defined as the time between their first complete response per indepedent review to relapse or any death in the absence of documented relapse

  2. Minimum Residual Disease Negative Remission Rate [ Time Frame: Up to 3 months ]
    Minimum residual disease negative remission rate is defined as incidence of a minimal residual disease response (MRD-). MRD- is defined as MRD < 10^(-4) per the standard assessment

  3. Allogeneic Stem Cell Transplant Rate [ Time Frame: Up to 24 months ]
    Allogeneic stem cell transplant rate is the incidence of Allogeneic SCT per the standard assessment

  4. Overall Survival [ Time Frame: Up to 15 years ]
    OS is defined as the time from KTE-C19 infusion to the date of death from any cause

  5. Relapse-free Survival (RFS) [ Time Frame: Up to 24 months ]
    RFS is defined as the time from the KTE-C19 infusion date to the date of disease relapse or death from any cause

  6. Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: Up to 15 years ]
  7. Incidence of anti-KTE-C19 antibodies [ Time Frame: Up to 15 years ]
  8. Changes over time in the EQ-5D score and VAS score (Phase 2) [ Time Frame: Up to 15 years ]
    The EQ-5D is a 2 page generic patient questionnaire for assessing the overall health status of a subject. The EQ-5D consists of a 5 dimension descriptive system including questions on mobility, selfcare, usual activities, pain/comfort, and anxiety/depression and a visual analogue scale (EQ VAS) which allows the respondent to record health on a vertical scale (eg, best health to worst health) thus allowing a quantitative measure of health outcome.

  9. Percentage of Participants Experiencing Common Terminology Criteria for Adverse Events (CTCAE) Grade Changes in Safety Laboratory Values [ Time Frame: Up to 15 years ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Key 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 2 or more lines of systemic therapy
    • Relapsed or refractory disease after allogeneic transplant provided individuals is at least 100 days from stem cell transplant at the time of enrollment
  2. Morphological disease in the bone marrow (≥ 5% blasts)
  3. 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
  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 alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN)
    • Total bilirubin ≤ 1.5 mg/dl, except in individuals 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 individuals previously treated with blinatumomab, CD19 tumor expression in bone marrow or peripheral blood.

Key Exclusion Criteria:

  1. Diagnosis of Burkitt's leukemia/lymphoma according to World Health Organization (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. Central nervous system (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 graft-versus-host disease (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. 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
  17. In the investigators judgment, the individuals 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

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

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): NCT02614066

Contact: Medical Information 844-454-KITE

United States, California
UC San Diego Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Contact: Krisma Montalvo    858-822-6843    kcmontalvo@AD.UCSD.EDU   
University of California Los Angeles (UCLA) Recruiting
Los Angeles, California, United States, 90095
Contact: Bruck Habtemariam   
Contact: Farzam Hariri, MD    310-206-5756   
University of California Irvine Medical Center Recruiting
Orange, California, United States, 92868
Contact: Blake Johnson   
Contact: Jinah Chung   
University of California Davis Comprehensive Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Kelly Jones    916-734-1093   
University of California San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Erika Cavallone    415-476-4765   
Contact: Rachel Johnson    415-476-4125   
United States, Florida
H Lee Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Matthew Scott    813-745-6939   
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Kunhee Lee   
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Alexis Small    773-702-9440   
Contact: Ray Robinson    773-702-2023   
Loyola University Recruiting
Chicago, Illinois, United States, 60660
Contact: Elizabeth Jasky    708-327-3095   
Principal Investigator: Patrick Stiff, MD         
United States, Maryland
University of Maryland Medical Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Sunita Philip    410-328-8199   
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Matthew Jacobs       Matthew_Jacobs@DFCI.HARVARD.EDU   
Contact: Victoria Allen       VALLEN2@PARTNERS.ORG   
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Mariam Shafiq   
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Phil Powell    314-747-2740   
Principal Investigator: Armin Ghobadi, MD         
United States, New York
Mount Sinai Tisch Cancer Institute Recruiting
New York, New York, United States, 10029
Contact: Megan Carmoody    212-241-1598   
Contact: Sonia Rau   
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Yvette Bernal    646-888-1370   
Principal Investigator: JaeHong Park, MD         
University of Rochester Recruiting
New York, New York, United States, 14642
Contact: Shawna Worth   
Contact: Robin Boerman   
United States, Tennessee
Sarah Cannon Recruiting
Nashville, Tennessee, United States, 37203
Contact: Tiffany Cardona    615-329-7254   
Contact: Jessica Johnson    615-329-7355   
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37212
Contact: Amber Lee   
United States, Texas
Baylor Charles A. Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
Contact: Erica Goetz   
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Emily Jones   
United States, Washington
Swedish Cancer Institute Recruiting
Seattle, Washington, United States, 98104
Contact: Neil Bailey    206-215-1471   
Seattle Cancer Center Recruiting
Seattle, Washington, United States, 98109
Contact: Lilli Johnson    206-667-3608   
Principal Investigator: Ryan Cassaday, MD         
Canada, Ontario
University Health Network - Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Nicole Luimes   
Principal Investigator: Andre Schuh, MD         
Sponsors and Collaborators
Kite, A Gilead Company
Study Director: Kite Study Director Kite, A Gilead Company

Responsible Party: Kite, A Gilead Company Identifier: NCT02614066     History of Changes
Other Study ID Numbers: KTE-C19-103
2015-005009-35 ( EudraCT Number )
First Posted: November 25, 2015    Key Record Dates
Last Update Posted: October 4, 2018
Last Verified: October 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic