Nilotinib Plus Pegylated Interferon-α2b in CML
|ClinicalTrials.gov Identifier: NCT01866553|
Recruitment Status : Terminated (insufficient enrollment)
First Posted : May 31, 2013
Last Update Posted : October 12, 2018
|Condition or disease||Intervention/treatment||Phase|
|Chronic Myeloid Leukemia||Drug: Nilotinib Drug: Pegylated interferon α-2b||Phase 2|
Study phase: Phase II.
Patients with suboptimal molecular response or stable detectable molecular residual disease after ≥ 2 years of treatment with imatinib (i.e. BCR ABL level between 0.01% and 1% IS).
To assess the effect of switching CML patients, who have been treated with imatinib ≥ 2 years and who have stable detectable molecular residual disease between 0.01-1.0% (IS), to the combination of Nilotinib and PegIFN, in terms of the proportion of patients who achieve confirmed MR4.0.
Single arm, open label, multicenter study to assess the efficacy, safety and tolerability of nilotinib 300 mg BID, alone and in combination with PegIFN 25 - 40 μg/week in patients not in CMR. Patients will be treated with nilotinib 300 mg BID at the beginning of the study to establish the tolerability before adding PegIFN. Combination treatment will be continued until Month 12, which is followed by monotherapy phase of nilotinib 300 mg BID. Overall study duration for the individual patient is 24 months.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II, Single Arm, Multicenter Study of Nilotinib in Combination With Pegylated Interferon-α2b in Patients With Suboptimal Molecular Response or Stable Detectable Molecular Residual Disease After at Least Two Years of Imatinib Treatment (NordDutchCML009)|
|Actual Study Start Date :||April 2013|
|Actual Primary Completion Date :||April 8, 2016|
|Actual Study Completion Date :||May 1, 2016|
Experimental: Nilotinib, Pegylated interferon α2b
Patients will be treated with nilotinib 300 mg BID during the first 3 months. Then the "combination phase" ensues with continued daily nilotinib 300 mg BID combined with PegIFN 25 ug/week for 3 months up to the Month 6 time point. If the patient has no more than grade 1 non-hematological toxicity or grade 2 hematological toxicity, the dose will be increased to 40 μg/w until Month 12. The "follow-up phase" with daily nilotinib 300 mg BID covers the next 12 months period (Month 12 to 24). until Month 12, which is followed by monotherapy phase of nilotinib 300 mg BID. Overall study duration for the individual patient is 24 months.
300 mg capsule BID oral use
Other Name: Tasigna
Drug: Pegylated interferon α-2b
25 - 40 microgram per week for subcutaneous use
- the proportion of patients achieving confirmed MR4.0. [ Time Frame: 12 months ]An interim efficacy analysis will be prepared after 40 patients have completed 12 months study treatment.If already a sufficient number of patients have achieved the efficacy endpoint i.e. a 25% increase in MR4.0 rate (from 48% in ENEStcmr to 73% in this study). Using Fleming's method, we have indication of superior efficacy of the combination if 29 or more patients achieve MR4.0, and thereafter may stop inclusion in the study.
- the number of patients experiencing grade 3 or more adverse events [ Time Frame: 6 months ]A safety interim analysis by a Safety Monitoring Committee (SMC) is planned after 15 patients have completed the Month 6 study assessment, i.e. after 3 months of the combination therapy. The study should be stopped if 4 out of 5, 6 out of 10 or 8 out of 15 patients experience grade 4 hematological toxicity, or grade 3 non hematological toxicity after 3 months of PegIFN treatment.
- The proportion of patients who complete the planned 9 months of combination therapy with PegIFN (i.e. to Month 12 assessment). [ Time Frame: 12 months ]An evaluation of the dose increase from 25 to 40 μg/week will be performed when 15 patients have passed the 9 month time point (i.e 3 months on 40 μg/week).
- Disease progression [ Time Frame: 24 months ]
- Overall Survival [ Time Frame: 24 months ]
- Quality of Life [ Time Frame: 24 months ]
- the adherence to combination treatment [ Time Frame: 24 months ]
- the percentage of patients who lose response after cessation of IFN between Month 12 and 18 [ Time Frame: 24 months ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01866553
|Aarhus University Hospital|
|Helsinki University Hospital|
|VU University Medical Center|
|Trondheim University Hospital|
|Uppsala University Hospital|
|Principal Investigator:||Jeroen Janssen, MD, PhD||VU University Medical Center|