Description:
The results of the International Randomized Study of Interferon and STI571 (IRIS) trial
indicate that in patients with chronic phase CML treated with first line imatinib,
achievement of a complete or partial cytogenetic response (CCyR or PCyR) at 12 months is
associated with a significantly better progression-free survival (PFS).
Second generation tyrosine kinase inhibitors such as nilotinib can overcome imatinib
resistance because of greater potency to bind to BCR-ABL. Recent results indicate that, in
patients with previously untreated chronic phase CML, nilotinib results in a faster and
higher rate of CCyR or PCyR than imatinib. However, nilotinib use is associated with diet
restriction and much higher financial cost.
The primary objective of this study is to evaluate the ability of imatinib to maintain a
complete cytogenetic response (CcyR) in patients who achieved a CCyR after 12 months of
first-line treatment with nilotinib.
Title
- Brief Title: Gleevec as Maintenance Therapy After Cytogenetic Response With Nilotinib in Newly Diagnosed Chronic Myelogenous Leukemia
- Official Title: Imatinib Mesylate (Glivec) as Maintenance Therapy After Cytogenetic Response With Nilotinib (AMN107, Tasigna) First Line in Newly Diagnosed Chronic Myelogenous Leukemia
Clinical Trial IDs
- ORG STUDY ID:
IM.AB.17
- NCT ID:
NCT01316250
Conditions
- Chronic Myelogenous Leukemia
Interventions
| Drug | Synonyms | Arms |
|---|
| Nilotinib | Tasigna, Gleevec | Nilotinib, cytogenetic response |
Purpose
The results of the International Randomized Study of Interferon and STI571 (IRIS) trial
indicate that in patients with chronic phase CML treated with first line imatinib,
achievement of a complete or partial cytogenetic response (CCyR or PCyR) at 12 months is
associated with a significantly better progression-free survival (PFS).
Second generation tyrosine kinase inhibitors such as nilotinib can overcome imatinib
resistance because of greater potency to bind to BCR-ABL. Recent results indicate that, in
patients with previously untreated chronic phase CML, nilotinib results in a faster and
higher rate of CCyR or PCyR than imatinib. However, nilotinib use is associated with diet
restriction and much higher financial cost.
The primary objective of this study is to evaluate the ability of imatinib to maintain a
complete cytogenetic response (CcyR) in patients who achieved a CCyR after 12 months of
first-line treatment with nilotinib.
Detailed Description
Imatinib mesylate selectively targets the causative BCR-ABL oncogene in CML. The results of
the IRIS trial indicate that in patients with chronic phase CML treated with first line
imatinib, achievement of a complete or partial cytogenetic response (CCyR or PCyR) at 12
months is associated with a significantly better progression free survival (PFS).
Second generation tyrosine kinase inhibitors such as nilotinib can overcome imatinib
resistance because of greater potency to bind to BCR-ABL. Recent results indicate that, in
patients with previously untreated chronic phase CML, nilotinib results in a faster and
higher rate of CCyR or PCyR than imatinib. However, nilotinib use is associated with diet
restriction and much higher financial cost. Hence, an appealing strategy is to achieve the
high rate of CCyR with first line nilotinib and then to maintain this response with long term
imatinib which is user friendly and cost-effective.
The primary objective is to test the ability of imatinib to maintain the cytogenetic response
in patients who achieved CCyR or PCyR at 12 months with first line nilotinib. The secondary
aims are to assess the effects of this strategy on molecular response, BCR-ABL mutations, and
CML progenitors.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Nilotinib, cytogenetic response | Other | Newly diagnosed CML patients | |
Eligibility Criteria
Inclusion Criteria:
1. Newly diagnosed untreated Philadelphia chromosome-positive CML (use of hydroxyurea for
<3 months is allowed) in chronic phase defined with the following criteria:
- <15% blasts in peripheral blood (PB) & bone marrow (BM)
- <30% blasts plus promyelocytes in PB & BM
- <20% basophils in PB
- ≥100 x 109/L platelets
- No evidence of extramedullary involvement, with the exception of liver & spleen
2. Patients (pts) ≥18 yrs of age
3. WHO Performance Status of ≤2
4. Pts must have the following laboratory values:
- Potassium within normal limits or corrected to within normal limits with
supplements prior to the first dose of study medication
- Total calcium (corrected for serum albumin) and magnesium within normal limits or
correctable with supplements
- Phosphorus ≥ lower limit of normal (LLN) or correctable with supplements
- ALT and AST ≤2.5 x upper limit of normal (ULN) or ≤5.0xULN if considered due to
tumor
- Alkaline phosphatase ≤2.5xULN
- Serum bilirubin ≤1.5xULN
- Serum Cr ≤1.5xULN or 24-hour Cr Cl ≥50 ml/min
- Serum amylase ≤1.5xULN and serum lipase ≤1.5xULN
5. Written signed informed consent prior to any study procedures
Exclusion Criteria:
1. Cytopathologically confirmed central nervous system (CNS) infiltration
2. Impaired cardiac function, including any one of the following:
- Left ventricle ejection fraction (LVEF) <45% or below the institutional lower
limit of the normal range (whichever is higher) as determined by MUGA scan or
echocardiogram
- Complete left bundle branch block
- Use of a pacemaker
- ST depression of >1mm in 2 or more leads and/or T wave inversions in 2 or more
contiguous leads
- Congenital long QT syndrome
- History of or presence of significant ventricular or atrial tachyarrhythmias
- Clinically significant resting bradycardia (<50 beats/min)
- QTc >450 msec on screening ECG
- Right bundle branch block plus left anterior hemiblock, bifascicular block
- Myocardial infarction within 12 months prior to starting nilotinib
- Unstable angina diagnosed or treated during the past 12 months
- Other clinically significant heart disease (e.g., congestive heart failure,
uncontrolled hypertension, or history of labile hypertension)
3. Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol) up to day
before study drug administration
4. Acute or chronic liver or renal disease considered unrelated to tumor such as active
Hepatitis A, B, or C
5. Other concurrent severe and/or uncontrolled medical conditions
6. Pts who are currently receiving treatment with any of the medications that have the
potential to prolong QT interval
7. Pts who have received any investigational drug ≤4 weeks or investigational cytotoxic
agent within 1 week (or who are within 5 half-lives of a previous investigational
cytotoxic agent) prior to starting study drug or who have not recovered from side
effects of such therapy
8. Pts who have received wide field radiotherapy ≤4 weeks or limited field radiation for
palliation <2 weeks prior to starting study drug or who have not recovered from side
effects of such therapy
9. Pts who have undergone major surgery ≤2 weeks prior to starting study drug or who have
not recovered from side effects of such therapy
10. Known diagnosis of HIV
11. Pt with a history of another malignancy that is currently clinically significant or
currently requires active intervention
12. Pts who are pregnant or breast feeding, or adults of reproductive potential not
employing an effective method of birth control (women of childbearing potential must
have a negative serum pregnancy test within 48 hrs prior to drug administration). Post
menopausal women must be amenorrheic for at least 12 months. Male & female pts must
agree to employ an effective method of birth control throughout the study and for 3
months following discontinuation of study drug
13. Pts unwilling or unable to comply with protocol
| Maximum Eligible Age: | 75 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | To test the ability of imatinib to maintain the cytogenetic response in patients who achieved complete cytogenetic response (CCyR) at 12 months with first line nilotinib. |
| Time Frame: | January 2010-January 2015 |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | To assess the effects of nilotinib followed by imatinib on molecular response |
| Time Frame: | January 2010-January 2015 |
| Safety Issue: | |
| Description: | |
| Measure: | To assess the effects of nilotinib followed by imatinib on BCR-ABL mutations |
| Time Frame: | January 2010-January 2015 |
| Safety Issue: | |
| Description: | |
Details
| Phase: | N/A |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | American University of Beirut Medical Center |
Trial Keywords
- chronic myelogenous leukemia
- nilotinib
- complete cytogenetic response
- imatinib mesylate
Last Updated
January 13, 2021
