Using imatinib to maintain treatment response in newly diagnosed chronic myelogenous leukemia patients after nilotinib

Imatinib Mesylate (Glivec) as Maintenance Therapy After Cytogenetic Response With Nilotinib (AMN107, Tasigna) First Line in Newly Diagnosed Chronic Myelogenous Leukemia

This study tests if switching to imatinib can help newly diagnosed chronic myelogenous leukemia patients keep their treatment benefits after starting with nilotinib.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: American University of Beirut Medical Center (other)
• Drugs / interventions: nilotinib, radiation, imatinib
• Locations: 1 site (Beirut)
• Trial ID: NCT01316250 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of imatinib mesylate in maintaining a complete cytogenetic response in patients with newly diagnosed chronic myelogenous leukemia (CML) who have achieved a complete or partial cytogenetic response after 12 months of treatment with nilotinib. The study aims to determine if transitioning to imatinib, a more cost-effective and user-friendly medication, can sustain the positive treatment outcomes achieved with nilotinib. Additionally, the trial will assess the impact of this strategy on molecular response and the presence of BCR-ABL mutations. The research is based on previous findings that suggest nilotinib offers a higher rate of cytogenetic response compared to imatinib.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older who have newly diagnosed Philadelphia chromosome-positive chronic phase CML.

Not a fit: Patients with advanced stages of CML or those who have previously received treatment for their condition may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a more affordable and manageable long-term treatment option for patients with chronic myelogenous leukemia.

How similar studies have performed: Previous studies have shown promising results with similar approaches, particularly in the context of transitioning from nilotinib to imatinib for maintaining treatment responses.

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

Where this trial is running

Beirut

• American University of Beirut Medical Center — Beirut, Lebanon (RECRUITING)

Study contacts

• Principal investigator: Ali Bazarbachi, MD, PhD — American University of Beirut Medical Center
• Study coordinator: Ali Bazarbachi, MD, PhD

Conditions: Chronic Myelogenous Leukemia, chronic myelogenous leukemia, nilotinib, complete cytogenetic response, imatinib mesylate