Chronic Myeloid LeukemiaPhase 2NCT01866553
Nilotinib Plus Pegylated Interferon-α2b in CML
A Phase 2 study testing Nilotinib and Pegylated interferon α-2b in people with Chronic Myeloid Leukemia, run by Amsterdam UMC, location VUmc at 5 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myeloid Leukemia
- What is being tested?
- Nilotinib and Pegylated interferon α-2b
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 5 sitesin 5 countries
- Study dates
- Apr 2013to 1 May 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Patient has given written informed consent
Who cannot join
- 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.
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- 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.
- Previous or active acute or chronic pancreatic disease.
- Another severe and/or life threatening medical disease.
- History of significant congenital or acquired bleeding disorder unrelated to cancer.
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug.
- Patients actively receiving therapy with strong CYP3A4 inhibitors and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug.
- Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug.
- Patients who are pregnant, breast feeding, of childbearing potential without a negative pregnancy test prior to baseline; male or female of childbearing potential unwilling to use contraceptive precautions throughout the trial (post menopausal women must be amenorrheic for at least 12 months to be considered of non childbearing potential).
- Interruption of imatinib therapy for a cumulative period in excess of 21 days in the preceding 3 months.
- Major toxicity on imatinib in past 3 months.
- History of non compliance, or other inability to grant informed consent.
- Past or present history of alcohol abuse, use of illicit drugs, or severe psychiatric disorders, including depression.
- Known hypersensitivity to any interferon preparation.
- Autoimmune hepatitis or a history of autoimmune disease.
- Pre existing thyroid disease unless it can be controlled with conventional treatment.
- Epilepsy and/or compromised central nervous system (CNS)function.
- HCV/HIV patients.
- Poorly controlled diabetes mellitus(i.e. HbA1c >9.0) or clinically relevant diabetic complications such as neuropathy, retinopathy, nephropathy, coronary or peripheral vascular disease.
Trial locations and contacts
5 sites in 5 countries.
5 sites in 5 countries
About this study
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)
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.
Read the detailed description
Study phase: Phase II.
Patient population:
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).
Study objective:
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.
Study design:
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.
- Conditions
- Chronic Myeloid Leukemia
- Being tested
- Nilotinib, Pegylated interferon α-2b
- Keywords
- CML, suboptimal molecular response, nilotinib, pegylated interferon α2b
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NilotinibDrug
Also called Tasigna
300 mg capsule BID oral use
Pegylated interferon α-2bDrug
Also called PegIFN, PegIntron, Pegylated interferon alfa-2b, Peginterferon alfa-2b
25 - 40 microgram per week for subcutaneous use
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Nilotinib; Drug: Pegylated interferon α-2b |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (2)
the number of patients experiencing grade 3 or more adverse events
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.
Measured: 6 months
The proportion of patients who complete the planned 9 months of combination therapy with PegIFN (i.e. to Month 12 assessment).
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).
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2013 (estimated)
- Study startApr 2013
- Primary completion8 Apr 2016
- Study completion1 May 2016
Why it stopped: insufficient enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- Uppsala University Hospital, Novartis, Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, J.J.W.M. Janssen, Amsterdam UMC, location VUmc
- Investigators
- Jeroen Janssen, MD, PhD, Principal investigator, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01866553
- Sponsor's protocol ID
- NordDutchCML009
- Other IDs
- 2012-004321-25, NTR 3732
- Status last verified
- Oct 2018
- First submitted
- 28 May 2013
- Last updated
- 12 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 37119314
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01866553
- Acronym / sponsor ID
- NordDutchCML009
- Conditions
- Chronic Myeloid Leukemia
- Keywords
- CML, suboptimal molecular response, nilotinib, pegylated interferon α2b
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: insufficient enrollment
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Collaborators
- Uppsala University Hospital, Novartis, Merck Sharp & Dohme LLC
- Study start
- Apr 2013 (actual)
- Primary completion
- 8 Apr 2016 (actual)
- Study completion
- 1 May 2016 (actual)
- First posted
- 31 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Study phase: Phase II.
Patient population:
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).
Study objective:
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.
Study design:
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nilotinib, Pegylated interferon α2b | Experimental | Drug: Nilotinib, Drug: Pegylated interferon α-2bPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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)
Key exclusion criteria (32 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NilotinibAlso: Tasigna300 mg capsule BID oral use | Drug | Nilotinib, Pegylated interferon α2b |
| Pegylated interferon α-2bAlso: PegIFN, PegIntron, Pegylated interferon alfa-2b, Peginterferon alfa-2b25 - 40 microgram per week for subcutaneous use | Drug | Nilotinib, Pegylated interferon α2b |
Primary outcome
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.
2 secondary outcomes
the number of patients experiencing grade 3 or more adverse events
Time frame: 6 months
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
Results and safety
The study was stopped early (reason given: insufficient enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2018.
- Derived from this study: PubMed 37119314Geelen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeroen Janssen, MD, PhD principal investigator
Amsterdam UMC, location VUmc
5 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nilotinib and Pegylated interferon α-2b in people with Chronic Myeloid Leukemia, run by Amsterdam UMC, location VUmc at 5 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Denmark, Finland, Netherlands, Norway, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: insufficient enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the proportion of patients achieving confirmed MR4.0. (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01866553, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2018.