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

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ClinicalTrials.gov Identifier: NCT02614066
Recruitment Status : Recruiting
First Posted : November 25, 2015
Last Update Posted : December 5, 2018
Sponsor:
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-X19 adult participants with relapsed/refractory (r/r) B-precursor acute lymphoblastic leukemia (ALL).

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Biological: KTE-X19 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-X19 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 : January 2020
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-X19
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-X19-related events with onset within the first 28 days following KTE-X19 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-X19 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-X19 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-X19 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
Criteria

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-X19
  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 ClinicalTrials.gov identifier (NCT number): NCT02614066


Contacts
Contact: Medical Information 844-454-KITE medinfo@kitepharma.com

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Sponsors and Collaborators
Kite, A Gilead Company
Investigators
Study Director: Kite Study Director Kite, A Gilead Company

Responsible Party: Kite, A Gilead Company
ClinicalTrials.gov 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: December 5, 2018
Last Verified: December 2018

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

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