An Open-label, Randomised Multicenter Phase 3b Study to Determine the Confirmed Rate of Molecular Response ≥ 4 Log (MR4) at Two Years
- Registration Number
- NCT02174445
- Lead Sponsor
- Prof. Dr. Nikolas von Bubnoff
- 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
- 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).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 14
Not provided
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Any previous treatment for CML other than Hydroxyurea, Imatinib or Interferon alpha
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Evidence of features of accelerated or blast phase at any time
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Previous loss of hematologic or cytogenetic response
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Concomitant medications known to be strong inducers or inhibitors of P450 Isoenzyme CYP3A4
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Finding of a secondary BCR-ABL resistance mutation at any time
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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
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Patients who had prior allogeneic, syngeneic, or autologous bone mar-row transplant or stem cell transplant
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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
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History of pancreatitis, chronic inflammatory diseases or autoimmune diseases
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Patients who underwent solid organ transplantation
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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)
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Known HIV and/or hepatitis B or C infection (testing is not mandatory)
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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
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Women who are pregnant or breast feeding
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Male/female patients of reproductive potential unwilling to practice a highly effective method of birth control
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History of noncompliance to medical regimens
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Treatment with another investigational product during this study or during the last 30 days prior to informed consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Nilotinib Nilotinib Nilotinib, 300mg, twice daily, maximum 6 years Imatinib Imatinib Imatinib 400-800mg, daily, maximum 6 years
- Primary Outcome Measures
Name Time Method Proportion of patients with confirmed MR4 after two years of study treatment 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
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (18)
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Universitätsklinikum Aachen
🇩🇪Aachen, Germany
Praxis Dr. Hauch
🇩🇪Erfurt, Germany
University Medical Center
🇩🇪Freiburg, Germany
Praxis für Hämatologie/Onkologie Dres. Rudolph, Sengpiel, von Verschuer
🇩🇪Essen, Germany
Internistische Schwerpunktpraxis Erlangen oncosearch
🇩🇪Erlangen, Germany
Universitätsklinikum Jena
🇩🇪Jena, Germany
Gemeinschaftspraxis Hämatologie/Onkologie
🇩🇪Magdeburg, Germany
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
Praxis Dr. Bruder / Dr. Heinrich / Prof. Bangerter
🇩🇪Augsburg, Germany
Universitätsklinikum Bonn
🇩🇪Bonn, Germany
Gemeinschaftspraxis
🇩🇪Dresden, Germany
Überörtliche Gemeinschaftspraxis Hämato-Onkologie Pasing/Fürstenfeldbruck
🇩🇪Munich, Germany
Universitätsklinik Köln
🇩🇪Köln, Germany
Onkologische Praxis Oldenburg
🇩🇪Oldenburg, Germany
Klinikum Mannheim GmbH Universitätsklinikum
🇩🇪Mannheim, Germany
Klinikum rechts der Isar, Technische Universität München
🇩🇪München, Germany
Medizinische Statistik Saarbrücken, GbR
🇩🇪Saarbrucken, Germany