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

NCT01316250 | Completed DMC

• 1 other identifier: IM.AB.17
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Myelogenous Leukemia

Keywords

chronic myelogenous leukemia; nilotinib; complete cytogenetic response; imatinib mesylate

Outcome Measures

Primary Outcomes (1)

• 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.

  January 2010-January 2015

Secondary Outcomes (2)

• To assess the effects of nilotinib followed by imatinib on molecular response

  January 2010-January 2015

• To assess the effects of nilotinib followed by imatinib on BCR-ABL mutations

  January 2010-January 2015

Study Arms (1)

Nilotinib, cytogenetic response

OTHER

Newly diagnosed CML patients

Drug: Nilotinib

Interventions

Nilotinib DRUG

Nilotinib 300 mg orally twice per day for 12 months followed by imatinib mesylate at a dose of 400 mg orally daily

Also known as: Tasigna, Gleevec

Nilotinib, cytogenetic response

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Patients (pts) ≥18 yrs of age
• WHO Performance Status of ≤2
• 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

You may not qualify if:

• Cytopathologically confirmed central nervous system (CNS) infiltration
• 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)
• Use of therapeutic coumarin derivatives (i.e., warfarin, acenocoumarol) up to day before study drug administration

Sponsors & Collaborators

• American University of Beirut Medical Center: lead

Study Sites (1)

American University of Beirut Medical Center

Beirut, Lebanon

Location

Related Publications (5)

• Buchdunger E, Cioffi CL, Law N, Stover D, Ohno-Jones S, Druker BJ, Lydon NB. Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther. 2000 Oct;295(1):139-45.

  PMID: 10991971 BACKGROUND

• Rosti G, Palandri F, Castagnetti F, Breccia M, Levato L, Gugliotta G, Capucci A, Cedrone M, Fava C, Intermesoli T, Cambrin GR, Stagno F, Tiribelli M, Amabile M, Luatti S, Poerio A, Soverini S, Testoni N, Martinelli G, Alimena G, Pane F, Saglio G, Baccarani M; GIMEMA CML Working Party. Nilotinib for the frontline treatment of Ph(+) chronic myeloid leukemia. Blood. 2009 Dec 3;114(24):4933-8. doi: 10.1182/blood-2009-07-232595. Epub 2009 Oct 12.

  PMID: 19822896 BACKGROUND

• Cortes JE, Jones D, O'Brien S, Jabbour E, Konopleva M, Ferrajoli A, Kadia T, Borthakur G, Stigliano D, Shan J, Kantarjian H. Nilotinib as front-line treatment for patients with chronic myeloid leukemia in early chronic phase. J Clin Oncol. 2010 Jan 20;28(3):392-7. doi: 10.1200/JCO.2009.25.4896. Epub 2009 Dec 14.

  PMID: 20008621 BACKGROUND

• Druker BJ, Guilhot F, O'Brien SG, Gathmann I, Kantarjian H, Gattermann N, Deininger MW, Silver RT, Goldman JM, Stone RM, Cervantes F, Hochhaus A, Powell BL, Gabrilove JL, Rousselot P, Reiffers J, Cornelissen JJ, Hughes T, Agis H, Fischer T, Verhoef G, Shepherd J, Saglio G, Gratwohl A, Nielsen JL, Radich JP, Simonsson B, Taylor K, Baccarani M, So C, Letvak L, Larson RA; IRIS Investigators. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006 Dec 7;355(23):2408-17. doi: 10.1056/NEJMoa062867.

  PMID: 17151364 BACKGROUND

• Ibrahim A, Moukalled N, Mahfouz R, El Cheikh J, Bazarbachi A, Abou Dalle I. Safety and Efficacy of Elective Switch from Nilotinib to Imatinib in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia. Clin Hematol Int. 2022 May 12;4(1-2):30-34. doi: 10.1007/s44228-022-00001-x. eCollection 2022 Jun.

  PMID: 35950205 DERIVED

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

nilotinib; Imatinib Mesylate

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Ali Bazarbachi, MD, PhD

  American University of Beirut Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 24, 2011
• First Posted: March 16, 2011
• Study Start: August 1, 2010
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: October 2, 2025

Record last verified: 2025-09

Locations

LE (1)