Clinical Trials /

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

NCT01316250

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.

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

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

DrugSynonymsArms
NilotinibTasigna, GleevecNilotinib, 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

NameTypeDescriptionInterventions
Nilotinib, cytogenetic responseOtherNewly diagnosed CML patients
  • Nilotinib

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

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