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Trial record 1 of 1 for:    NCT02174445
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An Open-label, Randomised Multicenter Phase 3b Study to Determine the Confirmed Rate of Molecular Response ≥ 4 Log (MR4) at Two Years (DECLINE)

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ClinicalTrials.gov Identifier: NCT02174445
Recruitment Status : Suspended (very slow recruitment rate and a lot of pat. didn't fulfil BCR-ABL requirements)
First Posted : June 25, 2014
Last Update Posted : January 29, 2019
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Prof. Dr. Nikolas von Bubnoff, University Hospital Freiburg

Brief Summary:
This is an open-label, multicenter, randomised phase 3b clinical trial of Imatinib 400 to 800 mg daily versus Nilotinib 300 mg two times daily in chronic phase CML patients with confirmed MMR without MR4.5

Condition or disease Intervention/treatment Phase
Chronic Myeloid Leukemia Drug: Imatinib Drug: Nilotinib Phase 3

Detailed Description:

This is an open-label, multicenter, randomised phase 3b clinical trial of Imatinib 400 to 800 mg daily versus Nilotinib 300 mg two times daily in chronic phase CML patients with confirmed MMR without MR4.5 (after having received Imatinib 400 to 800 mg daily for at least 18 months) to determine the proportion of patients with confirmed MR4 after two years. Patients in treatment arm A (Imatinib) who do not achieve confirmed MR4 2 years after randomisation will be offered cross-over from Imatinib 400 to 800 mg daily to Nilotinib 300 mg twice daily. One hundred thirty-two (132) patients will be included and randomised 1:1 to each treatment arm.

The study will be stratified by duration of Imatinib treatment before screen-ing (≤36 months / >36 months) as well as by the level of response at inclusion (MMR / MR4).


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 132 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Imatinib Continuation Versus Nilotinib 300 mg Twice Daily in Patients With Chronic Myeloid Leukemia (CML) in Chronic Phase and Major Molecular Re-sponse (MMR) Without Molecular Response ≥ 4.5 Log (MR4.5) Receiving Imatinib at a Dose of 400 to 800 mg Daily. An Open-label, Randomised Multicenter Phase 3b Study to Determine the Confirmed Rate of Molecular Response ≥ 4 Log (MR4) at Two Years
Actual Study Start Date : March 2014
Actual Primary Completion Date : December 2018
Estimated Study Completion Date : June 2019


Arm Intervention/treatment
Experimental: Imatinib
Imatinib 400-800mg, daily, maximum 6 years
Drug: Imatinib
Imatinib, 400 to 800 mg p.o., daily
Other Name: Glivec

Active Comparator: Nilotinib
Nilotinib, 300mg, twice daily, maximum 6 years
Drug: Nilotinib
300mg p.o., twice-daily
Other Name: Tasigna




Primary Outcome Measures :
  1. Proportion of patients with confirmed MR4 after two years of study treatment [ Time Frame: 2 years ]
    Proportion of patients with confirmed MR4 at two years of study treatment in both treatment arms. Confirmed MR4 at two years is defined as either BCR-ABL ≤ 0.01% IS at 21 and 24 months or BCR-ABL ≤ 0.01% IS at 24 months and confirmation within six weeks



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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

Inclusion criteria:

  1. Signed written informed consent
  2. Male or female patients aged >=18 years (without upper limit of age)
  3. ECOG performance status of 0 to 2
  4. CML in chronic phase, with chronic phase defined as blasts < 15% in blood and/or bone marrow and peripheral blood basophils < 20% and platelets ≥ 100 G/L
  5. Pretreatment with Imatinib with a treatment duration of at least 18 months at a dosage of 400 to 800 mg daily
  6. Major molecular response (MMR) without molecular response ≥ 4.5 log (MR4.5), i.e. BCR-ABL>0.0032% and ≤0.1% IS confirmed by central la-boratory at screening will be required for randomisation
  7. Patients must have a serum Creatinine of ≤ 1.5 x ULN, SGOT ≤ 1.5 x ULN, total bilirubin ≤ 1.5 x ULN (except known M. Gilbert), and Lipase ≤ 1.5 x ULN
  8. Women of child-bearing potential defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months, must have a negative serum pregnancy test during screening period. Male and fe-male patients of reproductive potential must agree to employ highly ef-fective methods of birth control throughout the study and for up to 3 months following discontinuation of study drug. Appropriate methods are e.g. a highly effective method of first choice, i.e. a method with a low failure rate (less than 1% per year) like sexual abstinence, com-bined oral contraceptives, implants, injectable, some Intra Uterine Devices (IUDs), vasectomized partner, in combination with a method of second choice like condom, diaphragm, or cup pessary with spermicidal foam/gel/film/cream/suppository.

Exclusion Criteria:

  1. Any previous treatment for CML other than Hydroxyurea, Imatinib or Interferon alpha
  2. Evidence of features of accelerated or blast phase at any time
  3. Previous loss of hematologic or cytogenetic response
  4. Concomitant medications known to be strong inducers or inhibitors of P450 Isoenzyme CYP3A4
  5. Finding of a secondary BCR-ABL resistance mutation at any time
  6. History of intolerance to Imatinib that required treatment interruption longer than 4 weeks (cumulative) or dose reductions to less than 400 mg daily for longer than 4 weeks (cumulative) during the last 12 months before informed consent
  7. Patients who had prior allogeneic, syngeneic, or autologous bone mar-row transplant or stem cell transplant
  8. Patients unwilling to or unable to comply with the planned therapeutic intervention or to comply with the study treatment visits including blood sample collection within the protocol
  9. History of pancreatitis, chronic inflammatory diseases or autoimmune diseases
  10. Patients who underwent solid organ transplantation
  11. Impaired cardiac function, including any of the following:

    • History of or presence of complete left bundle branch block, right bundle branch block plus left anterior hemi block, bifascicular block in screening ECG
    • Use of a cardiac pacemaker
    • ST depression of > 1mm in 2 or more leads and/or T wave inver-sions in 2 or more contiguous leads in screening ECG
    • Congenital Long QT Syndrome
    • QTc> 450 msec in the screening ECG
    • QT prolonging concomitant medication
    • History of or presence of significant ventricular or atrial tachy-arrhythmia in screening ECG
    • History of or presence of clinically significant resting bradycardia (< 50 beats per minute)
    • Myocardial infarction within 12 months prior to informed consent
    • Unstable angina diagnosed or treated during the past 12 months before informed consent
    • Other clinically significant heart disease (e.g., congestive heart fail-ure, uncontrolled hypertension, history of labile hypertension)
  12. Known HIV and/or hepatitis B or C infection (testing is not mandatory)
  13. Other malignancies within the past 3 years before informed consent except for adequately treated carcinoma of the cervix and basal or squamous cell carcinoma of the skin
  14. Women who are pregnant or breast feeding
  15. Male/female patients of reproductive potential unwilling to practice a highly effective method of birth control
  16. History of noncompliance to medical regimens
  17. Treatment with another investigational product during this study or during the last 30 days prior to informed consent

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): NCT02174445


Locations
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Germany
Universitätsklinikum Aachen
Aachen, Germany, 52074
Praxis Dr. Bruder / Dr. Heinrich / Prof. Bangerter
Augsburg, Germany, 86150
Universitätsklinikum Bonn
Bonn, Germany, 53105
Gemeinschaftspraxis
Dresden, Germany, 01307
Praxis Dr. Hauch
Erfurt, Germany, 99084
Internistische Schwerpunktpraxis Erlangen oncosearch
Erlangen, Germany, 91052
Praxis für Hämatologie/Onkologie Dres. Rudolph, Sengpiel, von Verschuer
Essen, Germany, 45136
University Medical Center
Freiburg, Germany, 79106
Universitätsklinikum Hamburg-Eppendorf
Hamburg, Germany, 20246
Universitätsklinikum Jena
Jena, Germany, 07747
Universitätsklinik Köln
Köln, Germany, 50937
Gemeinschaftspraxis Hämatologie/Onkologie
Magdeburg, Germany, 39104
Klinikum Mannheim GmbH Universitätsklinikum
Mannheim, Germany, 68167
Überörtliche Gemeinschaftspraxis Hämato-Onkologie Pasing/Fürstenfeldbruck
Munich, Germany, 81241
Klinikum rechts der Isar, Technische Universität München
München, Germany, 81675
Onkologische Praxis Oldenburg
Oldenburg, Germany, 26121
Medizinische Statistik Saarbrücken, GbR
Saarbrucken, Germany, 66113
Universitätsklinikum Ulm
Ulm, Germany, 89081
Sponsors and Collaborators
Prof. Dr. Nikolas von Bubnoff
Novartis
Investigators
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Principal Investigator: Nikolas von Bubnoff, Professor University Hospital Freiburg

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Responsible Party: Prof. Dr. Nikolas von Bubnoff, Mr., University Hospital Freiburg
ClinicalTrials.gov Identifier: NCT02174445     History of Changes
Other Study ID Numbers: CAMN107ADE18T
2013-000077-68 ( EudraCT Number )
DRKS00006285 ( Registry Identifier: DRKS )
First Posted: June 25, 2014    Key Record Dates
Last Update Posted: January 29, 2019
Last Verified: January 2019

Keywords provided by Prof. Dr. Nikolas von Bubnoff, University Hospital Freiburg:
Patients with CML in chronic phase
Imatinib
Nilotinib

Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action