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    The EU Clinical Trials Register currently displays   42760   clinical trials with a EudraCT protocol, of which   7042   are clinical trials conducted with subjects less than 18 years old.
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    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
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    EudraCT Number:2015-005010-30
    Sponsor's Protocol Code Number:KTE-C19-104
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2017-09-18
    Trial results
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2015-005010-30
    A.3Full title of the trial
    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)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study Evaluating the Safety and Efficacy of KTE-C19 in pediatric and adolescent Subjects with Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
    A.3.2Name or abbreviated title of the trial where available
    A.4.1Sponsor's protocol code numberKTE-C19-104
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02625480
    A.5.4Other Identifiers
    Name:IND NumberNumber:016675
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorKite Pharma Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportKite Pharma Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKite Pharma Inc.
    B.5.2Functional name of contact pointRegulatory Affairs
    B.5.3 Address:
    B.5.3.1Street Address2225 Colorado Avenue
    B.5.3.2Town/ citySanta Monica
    B.5.3.3Post codeCA 90404
    B.5.3.4CountryUnited States
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/15/1571
    D.3 Description of the IMP
    D.3.1Product nameKTE-C19
    D.3.2Product code KTE-C19
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNKTE-C19
    D.3.9.3Other descriptive nameKTE-C19
    D.3.9.4EV Substance CodeSUB182800
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2000000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D. cell therapy medicinal product No
    D. therapy medical product Yes
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. on Advanced therapies (CAT) has issued a classification for this product Yes
    D. classification and reference numberGene therapy medicinal product. Doc. Ref. EMA/CAT/360525/2015
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms Yes
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL)
    E.1.1.1Medical condition in easily understood language
    Cancers of white blood cells, collectively known as acute lymphoblastic leukemia.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10000844
    E.1.2Term Acute lymphoblastic leukaemia
    E.1.2System Organ Class 100000012958
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of phase 1 is to evaluate the safety of KTE-C19.
    The primary objective of phase 2 is to evaluate the efficacy of KTE-C19, as measured by the overall complete remission rate defined as complete remission (CR) and complete remission with partial hematologic recovery (CRh) in pediatric and adolescent subjects with r/r ALL
    E.2.2Secondary objectives of the trial
    Secondary objectives will include assessing the safety and tolerability of KTE-C19 and additional efficacy endpoints.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    101. 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 and off of immunosuppressive medications for at least 4 weeks prior to enrollment

    102. Morphological disease in the bone marrow (≥ 5% blasts)

    103. 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

    104. Ages 2-21 at the time of Assent or Consent per IRB guidelines

    105. 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 (Appendix C)

    106. ANC ≥ 500/uL unless in the opinion of the PI cytopenia is due to underlying leukemia and is potentially reversible with leukemia therapy

    107. Platelet count ≥ 50,000/uL unless in the opinion of the PI cytopenia is due to underlying leukemia and is potentially reversible with leukemia therapy

    108. Absolute lymphocyte count ≥200/µL

    109. Adequate renal, hepatic, pulmonary and cardiac function defined as:
    - Creatinine clearance (as estimated by Cockcroft Gault or Schwartz) ≥ 60 cc/min
    - Serum ALT and AST ≤ 5 x ULN
    - Total bilirubin ≤ 1.5 x ULN, except in subjects with Gilbert’s syndrome.
    - LVSF ≥ 30% or LVEF ≥ 50%, no evidence of pericardial effusion as determined by an ECHO and no clinical significant arrhythmias
    - No clinically significant pleural effusion
    - Baseline oxygen saturation ≥ 92% on room air

    110. Females of childbearing potential (defined as having first menses) must have a negative serum or urine pregnancy test

    111. In subjects previously treated with blinatumomab, CD19 tumor expression on blasts obtained from bone marrow or peripheral blood must be documented after completion of the most recent prior line of therapy. If CD19 expression is quantified, then blasts must be ≥ 90% CD19 positive.
    E.4Principal exclusion criteria
    201. Diagnosis of Burkitt’s leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis

    202. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years

    203. Isolated extramedullary disease

    204. CNS abnormalities
    a. Presence of CNS-3 disease, defined as detectable cerebrospinal blast cells in a sample of CSF with ≥5 WBCs per mm3 with or without neurological changes, and presence of CNS-2 disease defined as detectable cerebrospinal blast cells in a sample of CSF with < 5 WBCs per mm3 with neurological changes
    Note: Subjects with CNS-1 (no detectable leukemia in the CSF) and those with CNS-2 without clinically evident neurological changes are eligible to participate in the study.
    b. 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

    205. History of concomitant genetic syndrome associated with bone marrow failure such as Fanconi anemia, Kostmann syndrome or Shwachman-Diamond syndrome 206. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment

    207. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment.

    208. Primary immunodeficiency

    209. Known infection with HIV, hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive). A history of treated hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing.

    210. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the Kite medical monitor

    211. Prior medication:
    - Salvage chemotherapy (including TKIs for Ph+ ALL and blinatumomab) within 1 week prior to enrollment
    - Prior CD19 directed therapy other than blinatumomab
    - Alemtuzumab within 6 months prior to leukapheresis, clofarabine or cladribine within 3 months prior to leukapheresis, or PEG-asparaginase within 4 weeks prior to leukapheresis
    - Donor lymphocyte infusion (DLI) within 28 days prior to enrollment
    - Any drug used for GVHD within 4 weeks prior to enrollment (e.g. calcineurin inhibitors, methotrexate, mycophenolyate, rapamycin, thalidomide, or immunosuppressive antibodies such as rituximab, anti-tumor necrosis factor, anti-interleukin 6 or anti-interleukin 6 receptor)
    - At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy prior to enrollment (e.g. ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists etc)
    - Corticosteroid therapy at a pharmacologic dose (≥ 0.7 mg/kg/day of hydrocortisone or equivalent doses of corticosteroids) and other immunosuppressive drugs must be avoided for 7 days prior to enrollment

    212. 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

    213. 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

    214. Live vaccine ≤ 4 weeks prior to enrollment

    215. Females of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.

    216. 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.

    217. 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.

    218. 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
    E.5 End points
    E.5.1Primary end point(s)
    Phase 1: Incidence of adverse events (AEs) defined as dose-limiting toxicities (DLTs).
    Phase 2: Overall complete remission rate (CR + CRh) as defined by:
    - Less than or equal to 5% blasts in the bone marrow, and
    - No other evidence of morphologic disease*, and either
    - Platelets ≥100,000/µL and ANC ≥1,000/µL (CR) or
    - Platelets 50,000/µL - <100,000/µL and ANC 500/µL - <1000/µL (CRh)
    *All subjects must demonstrate a negative CSF assessment to be considered to achieve CR or CRh. Subjects with extramedullary disease detected through imaging at baseline also must meet the criteria for CR per Cheson 2007 in order to be considered to have CR or CRh.

    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary analyses will be conducted when all subjects have completed the 3 month disease response assessment, are lost to follow-up, withdraw from the study, or die, whichever occurs first.
    E.5.2Secondary end point(s)
    - Duration of Remission (DOR)
    - Minimal Residual Disease (MRD) negative rate
    - Allogeneic stem cell transplant (Allogeneic SCT) rate
    - Overall survival (OS)
    - Relapsed-free Survival (RFS)
    - Incidence of AEs and CTCAE grade changes in safety laboratory values
    - Incidence of anti-KTE-C19 antibodies.
    E.5.2.1Timepoint(s) of evaluation of this end point
    All subjects will be followed in the long term follow-up period for survival and disease status if applicable. Subjects will begin the long term follow-up period after they have completed the Month 3 visit of the post treatment assessment period (whether they have responded to
    treatment or went straight to the month 3 visit due to disease progression)
    - Every 3 months (± 2 weeks) through Month 18
    - Every 6 months (± 1 month) between Month 24 - Month 60
    - Beginning with year 6, Month 72 (± 3 months), subjects will return to the clinic 1 time annually up to 15 years after the last subject receives their KTE C19 infusion.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E. trial type description
    Phase I to assess safety, Phase II to assess efficacy of KTE-C19
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA8
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Defined as when the last subject is assessed or received an intervention for evaluation in the study, including survival assessments
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years15
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years15
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 75
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) Yes
    F. of subjects for this age range: 52
    F.1.1.6Adolescents (12-17 years) Yes
    F. of subjects for this age range: 23
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F. of subjects incapable of giving consent
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 16
    F.4.2.2In the whole clinical trial 75
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-08-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-01-31
    P. End of Trial
    P.End of Trial StatusOngoing
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