- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01316250
Gleevec as Maintenance Therapy After Cytogenetic Response With Nilotinib in Newly Diagnosed Chronic Myelogenous Leukemia
Imatinib Mesylate (Glivec) as Maintenance Therapy After Cytogenetic Response With Nilotinib (AMN107, Tasigna) First Line in Newly Diagnosed Chronic Myelogenous Leukemia
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.
Study Overview
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.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Ali Bazarbachi, MD, PhD
- Phone Number: 9613612434
- Email: bazarbac@aub.edu.lb
Study Locations
-
-
-
Beirut, Lebanon
- Recruiting
- American University of Beirut Medical Center
-
Contact:
- Ali Bazarbachi, MD, PhD
- Phone Number: 9613612434
- Email: bazarbac@aub.edu.lb
-
Principal Investigator:
- Ali Bazarbachi, MD, PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
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
- Serum Cr ≤1.5xULN or 24-hour Cr Cl ≥50 ml/min
- Serum amylase ≤1.5xULN and serum lipase ≤1.5xULN
- Written signed informed consent prior to any study procedures
Exclusion Criteria:
- 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
- Acute or chronic liver or renal disease considered unrelated to tumor such as active Hepatitis A, B, or C
- Other concurrent severe and/or uncontrolled medical conditions
- Pts who are currently receiving treatment with any of the medications that have the potential to prolong QT interval
- 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
- 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
- Pts who have undergone major surgery ≤2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
- Known diagnosis of HIV
- Pt with a history of another malignancy that is currently clinically significant or currently requires active intervention
- 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
- Pts unwilling or unable to comply with protocol
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Nilotinib, cytogenetic response
Newly diagnosed CML patients
|
Nilotinib 300 mg orally twice per day for 12 months followed by imatinib mesylate at a dose of 400 mg orally daily
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
January 2010-January 2015
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To assess the effects of nilotinib followed by imatinib on molecular response
Time Frame: January 2010-January 2015
|
January 2010-January 2015
|
To assess the effects of nilotinib followed by imatinib on BCR-ABL mutations
Time Frame: January 2010-January 2015
|
January 2010-January 2015
|
Collaborators and Investigators
Investigators
- Principal Investigator: Ali Bazarbachi, MD, PhD, American University of Beirut Medical Center
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Disease Attributes
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Chronic Disease
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Imatinib Mesylate
Other Study ID Numbers
- IM.AB.17
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Chronic Myelogenous Leukemia
-
National Cancer Institute (NCI)CompletedChildhood Chronic Myelogenous Leukemia | Chronic Phase Chronic Myelogenous Leukemia | Relapsing Chronic Myelogenous Leukemia | Chronic Myelogenous Leukemia, BCR-ABL1 PositiveUnited States
-
National Cancer Institute (NCI)TerminatedAccelerated Phase Chronic Myelogenous Leukemia | Chronic Phase Chronic Myelogenous Leukemia | Relapsing Chronic Myelogenous Leukemia | Chronic Myelogenous Leukemia, BCR-ABL1 PositiveUnited States
-
National Cancer Institute (NCI)CompletedChronic Phase Chronic Myelogenous Leukemia | Relapsing Chronic Myelogenous Leukemia | Chronic Myelogenous Leukemia, BCR-ABL1 PositiveUnited States
-
National Cancer Institute (NCI)CompletedChildhood Chronic Myelogenous Leukemia | Chronic Phase Chronic Myelogenous Leukemia | Chronic Myelogenous Leukemia, BCR-ABL1 PositiveUnited States
-
National Cancer Institute (NCI)TerminatedAccelerated Phase Chronic Myelogenous Leukemia | Chronic Phase Chronic Myelogenous Leukemia | Relapsing Chronic Myelogenous Leukemia | Chronic Myelogenous Leukemia, BCR-ABL1 Positive | Blastic Phase Chronic Myelogenous LeukemiaUnited States
-
National Cancer Institute (NCI)CompletedChronic Phase Chronic Myelogenous Leukemia | Chronic Myelogenous Leukemia, BCR-ABL1 PositiveUnited States
-
National Cancer Institute (NCI)CompletedAccelerated Phase Chronic Myelogenous Leukemia | Childhood Chronic Myelogenous Leukemia | Relapsing Chronic Myelogenous Leukemia | Chronic Myelogenous Leukemia, BCR-ABL1 Positive | Blastic Phase Chronic Myelogenous LeukemiaUnited States
-
M.D. Anderson Cancer CenterNovartisCompletedLeukemia, Myelogenous, ChronicUnited States
-
The University of Hong KongUnknownCessation of Tyrosine Kinase Inhibitors in Patients With Chronic-phase Chronic Myelogenous LeukaemiaLeukemia, Myelogenous, Chronic PhaseHong Kong
-
Assiut UniversityUnknownChronic Phase Chronic Myelogenous Leukemia
Clinical Trials on Nilotinib
-
Niguarda HospitalCompletedLeukemia, Myeloid, Chronic-PhaseItaly
-
Novartis PharmaceuticalsTerminatedPulmonary Arterial HypertensionSwitzerland, United States, Germany, Singapore, Korea, Republic of, Canada
-
Georgetown UniversityUnknownParkinson Disease | Parkinsons Disease With DementiaUnited States
-
XSpray MicroparticlesCompleted
-
KeifeRx, LLCWorldwide Clinical Trials; Life Molecular Imaging GmbH; Sun Pharmaceuticals Industries...Not yet recruiting
-
Shenzhen Second People's HospitalDongguan People's Hospital; Zhongshan People's Hospital, Guangdong, China; The... and other collaboratorsRecruitingChronic Myeloid Leukemia, Chronic Phase | NilotinibChina
-
Andrew J. Wagner, MD, PhDMassachusetts General Hospital; Novartis; Brigham and Women's HospitalActive, not recruitingTenosynovial Giant Cell Tumor | Pigmented Villonodular Synovitis | Diffuse-type Giant Cell TumorUnited States
-
Novartis PharmaceuticalsNo longer availableHypereosinophilic Syndrome (HES)
-
Novartis PharmaceuticalsNo longer availableAcute Lymphoblastic Leukemia (ALL)
-
Novartis PharmaceuticalsCompleted