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Gleevec as Maintenance Therapy After Cytogenetic Response With Nilotinib in Newly Diagnosed Chronic Myelogenous Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by American University of Beirut Medical Center
Sponsor:
Information provided by (Responsible Party):
Dr. Ali Bazarbachi, American University of Beirut Medical Center
ClinicalTrials.gov Identifier:
NCT01316250
First received: February 24, 2011
Last updated: September 14, 2013
Last verified: September 2013
  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.


Condition Intervention
Chronic Myelogenous Leukemia
Drug: Nilotinib

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Imatinib Mesylate (Glivec) as Maintenance Therapy After Cytogenetic Response With Nilotinib (AMN107, Tasigna) First Line in Newly Diagnosed Chronic Myelogenous Leukemia

Resource links provided by NLM:


Further study details as provided by American University of Beirut Medical Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the effects of nilotinib followed by imatinib on molecular response [ Time Frame: January 2010-January 2015 ] [ Designated as safety issue: No ]
  • To assess the effects of nilotinib followed by imatinib on BCR-ABL mutations [ Time Frame: January 2010-January 2015 ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: August 2010
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Nilotinib, cytogenetic response Drug: Nilotinib
Nilotinib 300 mg orally twice per day for 12 months followed by imatinib mesylate at a dose of 400 mg orally daily
Other Name: Tasigna, Gleevec

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 and bone marrow
    • < 30% blasts plus promyelocytes in peripheral blood and bone marrow
    • < 20% basophils in the peripheral blood
    • ≥ 100 x 109/L (≥ 100,000/mm3) platelets
    • No evidence of extramedullary leukemic involvement, with the exception of liver and spleen
  2. Males or females ≥18 years of age
  3. WHO Performance Status of ≤ 2
  4. Patients 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) within normal limits or correctable with supplements
    • Magnesium within normal limits or corrected to within normal limits with supplements prior to the first dose of study medication
    • Phosphorus ≥ lower limit of normal (LLN) or correctable with supplements
    • ALT and AST ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if considered due to tumor
    • Alkaline phosphatase ≤ 2.5 x ULN unless considered due to tumor
    • Serum bilirubin ≤ 1.5 x ULN
    • Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 ml/min
    • Serum amylase ≤ 1.5 x ULN and serum lipase ≤ 1.5 x ULN
  5. Written signed and dated informed consent prior to any study procedures being performed

Exclusion Criteria:

  1. Cytopathologically confirmed central nervous system (CNS) infiltration (in absence of suspicion of CNS involvement, lumbar puncture is not required).
  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 cardiac 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 per minute)
    • QTc >450 msec on screening ECG (using the QTcF formula)
    • 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, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
  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 (e.g., uncontrolled diabetes, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
  6. Patients who are currently receiving treatment with any of the medications that have the potential to prolong the QT interval.
  7. Patients 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. Patients 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. Patients 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 human deficiency virus (HIV) infection
  11. Patient with a history of another malignancy that is currently clinically significant or currently requires active intervention.
  12. Patients 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 administration of nilotinib). Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective method of birth control throughout the study and for 3 months following discontinuation of study drug.
  13. Patients unwilling or unable to comply with the protocol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01316250

Contacts
Contact: Ali Bazarbachi, MD, PhD 9613612434 bazarbac@aub.edu.lb

Locations
Lebanon
American University of Beirut Medical Center Recruiting
Beirut, Lebanon
Contact: Ali Bazarbachi, MD, PhD    9613612434    bazarbac@aub.edu.lb   
Principal Investigator: Ali Bazarbachi, MD, PhD         
Sponsors and Collaborators
American University of Beirut Medical Center
  More Information

Publications:

Responsible Party: Dr. Ali Bazarbachi, Professor, American University of Beirut Medical Center
ClinicalTrials.gov Identifier: NCT01316250     History of Changes
Other Study ID Numbers: IM.AB.17
Study First Received: February 24, 2011
Last Updated: September 14, 2013
Health Authority: Lebanon: Institutional Review Board

Keywords provided by American University of Beirut Medical Center:
chronic myelogenous leukemia
nilotinib
complete cytogenetic response
imatinib mesylate

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Imatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014