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Trial record 15 of 80 for:    "Adult Acute Lymphocytic Leukemia" | "Antineoplastic Agents, Hormonal"

A Phase III Randomized Trial of the Reduction of Chemotherapy in Philadelphia Chromosome-positive ALL of Young Adults (GRAAPH2014)

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ClinicalTrials.gov Identifier: NCT02611492
Recruitment Status : Recruiting
First Posted : November 20, 2015
Last Update Posted : October 21, 2019
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE November 19, 2015
First Posted Date  ICMJE November 20, 2015
Last Update Posted Date October 21, 2019
Study Start Date  ICMJE April 2016
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 25, 2015)
Major Molecular Response (MMolR) [ Time Frame: 4 cycles (4 months) ]
defined as a breakpoint cluster region (BCR)-Abelson (ABL) ratio < 0.1% in the bone marrow sample of MRD4
Original Primary Outcome Measures  ICMJE
 (submitted: November 19, 2015)
Major Molecular Response (MMolR) [ Time Frame: 4 cycles (4 months) ]
defined as a BCR-ABL/ABL ratio < 0.1% in the bone marrow sample of MRD4
Change History Complete list of historical versions of study NCT02611492 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 25, 2015)
  • Complete remission after cycle 1 [ Time Frame: day 28 ]
  • Cumulative incidence of treatment- and transplantation-related mortality [ Time Frame: 2 years ]
  • Cumulative incidence of relapse [ Time Frame: 10 years ]
  • Relapse free survival [ Time Frame: 10 years ]
  • Event-free survival [ Time Frame: 10 years ]
  • overall survival [ Time Frame: 10 years ]
  • T315I mutation [ Time Frame: 10 years ]
    mutations will be assessed by Reverse transcription Quantitative Polymerase Chain Reaction (RQ-PCR) sequencing in case of progression or relapse
  • Toxicity [ Time Frame: 12 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 19, 2015)
  • Complete remission after cycle 1 [ Time Frame: day 28 ]
  • Cumulative incidence of treatment- and transplantation-related mortality [ Time Frame: 2 years ]
  • Cumulative incidence of relapse [ Time Frame: 10 years ]
  • Relapse free survival [ Time Frame: 10 years ]
  • Event-free survival [ Time Frame: 10 years ]
  • overall survival [ Time Frame: 10 years ]
  • T315I mutation [ Time Frame: 10 years ]
    mutations will be assessed by RQ-PCR sequencing in case of progression or relapse
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase III Randomized Trial of the Reduction of Chemotherapy in Philadelphia Chromosome-positive ALL of Young Adults
Official Title  ICMJE A Phase III Study, Randomized, to Evaluate the Reduction of Chemotherapy Intensity in Association With Nilotinib (Tasigna®) in Philadelphia Chromosome-positive (Ph+) ALL of Young Adults (18-59 Years Old) (GRAAPH-2014)
Brief Summary The Primary objective is to assess the non-inferiority of the experimental arm (arm B) compared to the control arm (arm A) in terms of Major Molecular Response (MMolR) after the 4th cycle (MRD4) in patients aged 18-59 years old with de novo Philadelphia positive (Ph+) acute lymphoblastic leukemia (ALL)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Philadelphia Chromosome Positive Adult Acute Lymphoblastic Leukemia
Intervention  ICMJE
  • Drug: Nilotinib
    400 mg/12h per os D1 to D28 cycles 1-4 300 mg/12h per os D1-D14 interphase
  • Drug: Methotrexate
    1 g/m2 continuous Intravenous Infusion (CIV) D1 cycles 2 and 4 25 mg/m2 per os D1, D8 interphase
  • Drug: Aracytine (Ara C)
    Age<45 years: 3 mg/m2/12h D2, D3 cycles 2 and 4 Age>=45 years: 1.5 mg/m2/12h D2, D3 cycles 2 and 4
  • Drug: Granulocyte Colony-Stimulating Factor (G-CSF)
    5µg/kg/d (SC) D6 until neutrophils > 1 G/L D15 cycles 1 and 3; D6 cycles 2 and 4
  • Drug: Depomedrol
    40 mg + methotrexate 15 mg + Aracytine (AraC) 40mg IT cycle 1: D1, D8, D15 IT cycles 2 and 4: D9 IT cycle 3: D1
  • Drug: Dexamethasone
    40 mg per os, D1-D2, D8-D9, D15-D16, D22-D23, cycles 1 and 3
  • Drug: Vincristine
    2 mg total dose IV, D1 D8 D15 D22 cycles 1 and 3
  • Drug: Imatinib
    300 mg/12h per os in post-SCT maintenance therapy for during at least 2 years
  • Drug: 6 Mercaptopurine (6MP)
    60 mg/m2 per os, D1 to D14, interphase
Study Arms  ICMJE
  • Active Comparator: Intensive Arm (A)

    4 cycles + 2 interphases +Hematopoietic Stem Cell Transplantation (SCT)

    + Post-SCT Maintenance

    Interventions:
    • Drug: Nilotinib
    • Drug: Methotrexate
    • Drug: Aracytine (Ara C)
    • Drug: Granulocyte Colony-Stimulating Factor (G-CSF)
    • Drug: Depomedrol
    • Drug: Dexamethasone
    • Drug: Vincristine
    • Drug: Imatinib
    • Drug: 6 Mercaptopurine (6MP)
  • Experimental: Light Arm (B)

    4 cycles + 2 interphases +Hematopoietic Stem Cell Transplantation (SCT)

    + Post-SCT Maintenance

    Interventions:
    • Drug: Nilotinib
    • Drug: Methotrexate
    • Drug: Granulocyte Colony-Stimulating Factor (G-CSF)
    • Drug: Depomedrol
    • Drug: Dexamethasone
    • Drug: Vincristine
    • Drug: Imatinib
    • Drug: 6 Mercaptopurine (6MP)
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: November 19, 2015)
265
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2025
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Patient

  1. Whose blood and bone marrow explorations have been completed before the steroids prephase
  2. Aged 18-59 years old with newly-diagnosed non previously treated Ph+ ALL according to WHO 2008 criteria (confirmed diagnosis of the Philadelphia chromosome defined by the reciprocal translocation of chromosomes 9 and 22, t(9;22) and/or presence of the BCR-ABL molecular maker)
  3. With ≥ 20% bone marrow blasts
  4. With Eastern Cooperative Oncology Group (ECOG) Performans Status ≤ 3
  5. With or without central nervous system (CNS) or testis involvement
  6. Without evolving cancer (except basal cell carcinoma of the skin or "in situ" carcinoma of the cervix) or its chemo- or radio-therapy should be finished at least since 6 months.
  7. Having received no previous treatment for this hematological disease (including IT injection)
  8. Having signed written informed consent
  9. With efficient contraception for women of childbearing age (excluding estrogens and IUD)
  10. With health insurance coverage
  11. Who have received (or being receiving) the recommended steroid prephase.

Note 1: Secondary ALL (antecedent of chemo- or radio-therapy) can be included Note 2: In case of high vascular risk (see section "study management") the patient will not be able to receive nilotinib unless an ultra sound Doppler of the neck and lower limbs has been performed during the pre-phase and treatment validated by the medical coordinators of the protocol via the secretariat.

Exclusion Criteria:

Patient:

  1. Previously treated with Tyrosine Kinase Inhibitor (TKI)
  2. With another active malignancy
  3. With general or visceral contra-indication to intensive therapy (except if considered related to the ALL):

    1. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2.5 x upper limit of normal range (ULN)
    2. Total bilirubin > 1.5 x ULN
    3. Creatinine > 1.5 x ULN or creatinine clearance <50 mL/mn
    4. Serum amylase or lipase > 1.5 x ULN or antecedents of acute pancreatitis
  4. With heart failure, including at least one of the following criteria:

    1. Left ventricular ejection fraction (LVEF) <50% or below the lowest normal threshold, as determined by ECG or heart failure (NYHA grade III or IV)
    2. Impossibility to measure the QT interval on ECG
    3. Complete left bundle branch block
    4. Pacemaker
    5. Congenital long QT syndrome of known familial antecedents of long QT syndrome
    6. Antecedents or current ventricular or atrial tachyarrhythmia, clinically significant
    7. Baseline bradycardia (<50 bpm) clinically significant
    8. Corrected QT interval (QTc)> 450 msec established on the mean of 3 baseline ECG
    9. Antecedents of myocardial infarct in the past 6 months
    10. Instable angor within the past 12 months
    11. Any heart condition clinically significant (i.e. congestive heart failure, uncontrolled hypertension)
  5. Active uncontrolled infection, any other concurrent disease deemed to interfere with the conduct of the study as judged by the investigator
  6. Severe evolving infection, or known HIV or Human T-Lymphotropic Virus type I (HTLV1) seropositivity, or active infection by hepatitis B or C virus
  7. Pregnant (beta-HCG) or nursing woman
  8. Women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least three months thereafter. Patient not willing to ensure not to beget a child during participation in the study and at least three months thereafter.
  9. Having received an investigational treatment or participation in another trial within 30 days prior to entering this study.
  10. Not able to bear with the procedures or the frequency of visits planned in the trial.
  11. Unable to consent, under tutelage or curators, or judiciary safeguard
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 59 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Hervé Dombret, MDPhD +33 (0)1 57 27 68 47 herve.dombret@aphp.fr
Contact: Véronique Lhéritier +33(0)4 78 86 22 39 veronique.lheritier@chu-lyon.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02611492
Other Study ID Numbers  ICMJE AOM12629_1
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date September 2019

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