NCT01866553

Brief Summary

The purpose of this trial 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.

Trial Health

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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Apr 2013

Typical duration for phase_2

Geographic Reach
5 countries

5 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2013

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

May 28, 2013

Completed
3 days until next milestone

First Posted

Study publicly available on registry

May 31, 2013

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 8, 2016

Completed
23 days until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2016

Completed
Last Updated

October 12, 2018

Status Verified

October 1, 2018

Enrollment Period

3 years

First QC Date

May 28, 2013

Last Update Submit

October 9, 2018

Conditions

Chronic Myeloid Leukemia

Keywords

CMLsuboptimal molecular responsenilotinibpegylated interferon α2b

Outcome Measures

Primary Outcomes (1)

  • the proportion of patients achieving confirmed MR4.0.

    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.

    12 months

Secondary Outcomes (2)

  • the number of patients experiencing grade 3 or more adverse events

    6 months

  • The proportion of patients who complete the planned 9 months of combination therapy with PegIFN (i.e. to Month 12 assessment).

    12 months

Other Outcomes (5)

  • Disease progression

    24 months

  • Overall Survival

    24 months

  • Quality of Life

    24 months

  • +2 more other outcomes

Study Arms (1)

Nilotinib, Pegylated interferon α2b

EXPERIMENTAL

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.

Drug: NilotinibDrug: Pegylated interferon α-2b

Interventions

NilotinibDRUG

300 mg capsule BID oral use

Also known as: Tasigna
Nilotinib, Pegylated interferon α2b
Pegylated interferon α-2bDRUG

25 - 40 microgram per week for subcutaneous use

Also known as: PegIFN, PegIntron, Pegylated interferon alfa-2b, Peginterferon alfa-2b
Nilotinib, Pegylated interferon α2b

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients ≥ 18 years
  • At diagnosis CML in chronic phase
  • Documented complete cytogenetic response by bone marrow (standard cytogenetics) or peripheral blood BCR ABL \<1% IS
  • Persistent disease demonstrated by two PCR positive tests (i.e. BCR ABL level between 0.01% and 1% IS) which have been performed during the past 9 months and more than 10 weeks apart. One of these should be performed within 1 month of registration
  • Treatment with imatinib for at least 2 years with 400 mg and at a stable dose (i.e. the dose has not changed in the previous 6 months)
  • No other current or planned anti leukemia therapies
  • ECOG Performance status 0,1, or 2
  • Adequate organ function as defined by:
  • Total bilirubin \<1.5 x ULN. Does not apply to patients with isolated hyperbilirubinemia (e.g. Gilbert's disease) grade \<3.
  • ASAT and ALAT \<2.5 x ULN.
  • Serum amylase and lipase ≤1.5 x ULN.
  • Alkaline phosphatase ≤2.5 x ULN.
  • Creatinine clearance \>30 ml/min.
  • Mg++, K+ ≥LLN.
  • Life expectancy \> 12 months in the absence of any intervention
  • +1 more criteria

You may not qualify if:

  • Prior accelerated phase or blast crisis.
  • Patient has received another investigational agent within last 6 months.
  • Previous treatment with nilotinib or dasatinib.
  • Prior stem cell transplantation.
  • Impaired cardiac function including any one of the following:
  • Inability to monitor the QT/QTc interval on ECG.
  • Long QT syndrome or a known family history of long QT syndrome.
  • Clinically significant resting brachycardia (\<50 bpm).
  • QTc \>450 msec on baseline ECG (using the QTcF formula). If QTcF \>450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re screened for QTc.
  • Myocardial infarction within 12 months prior to starting study.
  • Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension).
  • History of or presence of clinically significant ventricular or atrial tachyarrhythmias.
  • Known atypical BCR ABL transcript not quantifiable by standard RQ PCR
  • History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or carcinoma in situ of cervix uteri or breast.
  • Acute liver disease or cirrhosis.
  • +17 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Aarhus University Hospital

Aarhus, Denmark

Location

Helsinki University Hospital

Helsinki, Finland

Location

VU University Medical Center

Amsterdam, Netherlands

Location

Trondheim University Hospital

Trondheim, Norway

Location

Uppsala University Hospital

Uppsala, Sweden

Location

Related Publications (1)

  • Geelen IGP, Gullaksen SE, Ilander MM, Olssen-Stromberg U, Mustjoki S, Richter J, Blijlevens NMA, Smit WM, Gjertsen BT, Gedde-Dahl T, Markevarn B, Koppes MMA, Westerweel PE, Hjorth-Hansen H, Janssen JJWM. Switching from imatinib to nilotinib plus pegylated interferon-alpha2b in chronic phase CML failing to achieve deep molecular response: clinical and immunological effects. Ann Hematol. 2023 Jun;102(6):1395-1408. doi: 10.1007/s00277-023-05199-1. Epub 2023 Apr 29.

    PMID: 37119314DERIVED

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

nilotinibpeginterferon alfa-2b

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsMyeloproliferative DisordersBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Jeroen Janssen, MD, PhD

    Amsterdam UMC, location VUmc

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD

Study Record Dates

First Submitted

May 28, 2013

First Posted

May 31, 2013

Study Start

April 1, 2013

Primary Completion

April 8, 2016

Study Completion

May 1, 2016

Last Updated

October 12, 2018

Record last verified: 2018-10

Locations

NO(1)SE(1)NL(1)FI(1)DK(1)