Nilotinib in PH+, BCR-, ABL+ CML Patients (CML0811)

Tracking Information
First Submitted Date ICMJE	February 9, 2012
First Posted Date ICMJE	February 17, 2012
Last Update Posted Date	March 22, 2018
Actual Study Start Date ICMJE	January 2012
Actual Primary Completion Date	November 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: February 16, 2012)	Complete molecular response [ Time Frame: At 24 months of treatment ]; To assess the complete molecular response (CMR4) rate at 24 months of treatment. For the purpose of this protocol, CMR is defined as a negative results of quantitative RT-PCR for BCR-ABL transcripts in a peripheral blood sample of at least 10 ml with a minimum sensitivity of 1:10,000, that corresponds to at least a 4-log reduction (hence, CMR4)
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01535391 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: February 16, 2012)	Toxicity [ Time Frame: At three years from study entry ]Number of toxic events; Compliance [ Time Frame: At 3 years from study entry ]Number of fully compliant patients and number of patients who do not comply with treatment; The complete cytogenetic response (CCgR) rate [ Time Frame: At 3, 6, 12, 18 and 24 months from study entry ]; The rate and the degree of molecular response [ Time Frame: At 3, 6, 12, 18 and 24 months from study entry ]; The time to CCgR, the time to MMR and the time to CMR [ Time Frame: baseline ]; Overall Survival (OS) [ Time Frame: At three years from study entry ]From the date of the first nilotinib dose to death; Progression Free Survival (PFS) [ Time Frame: At three years from study entry ]From the date of the first nilotinib dose to progression to AP or BP or death; Failure Free Survival (FFS) [ Time Frame: At three years from study entry ]From the date of the first nilotinib dose to failure* or progression or death; Event Free Survival (EFS) [ Time Frame: At three years from study entry ]From the date of the first nilotinib to any event. Including treatment discontinuation for adverse events, failure, progression to AP or BP, or death, whichever comes first.; Patient-reported quality of life (QoL) [ Time Frame: At baseline and then at 3, 6, 12, 18 and 24 months ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Nilotinib in PH+, BCR-, ABL+ CML Patients
Official Title ICMJE	The Protein Tyrosine Kinase Inhibitor Nilotinib as First-line Treatment of Ph+, BCR-, ABL+ Chronic Myeloid Leukemia (CML) in Early Chronic Phase: a Phase IIIb, Multicenter Study to Assess the Complete Molecular Response
Brief Summary	This study is an open-label, multicentric, phase IIIb study of NILOTINIB administered orally twice daily for 24 months and indefinitely if it is in the interest of the patient. The primary objective of the trial is to evaluate the efficacy of nilotinib, 300 mg twice daily with dose increase to 400 mg twice daily in case of suboptimal response or failure (excluding patients who will fail for progression to ABP), in a population of patients with Ph-positive, BCR-ABL positive CML in early CP.
Detailed Description	This study is an open-label, multicentric, phase IIIb study of NILOTINIB administered orally at the dose of 300 mg twice daily (total daily dose 600 mg daily) for 24 months (study core), and indefinitely if it is in the interest of the patient (the drug will be given free-of-charge after 24 months to all those patients achieving the CMR4 at 24 months and in absence of safety concerns). Nilotinib dose is increased to 400 mg BID in case of suboptimal response or failure (with the exception of patients who will fail for progression to ABP: in case of progression to ABP, the patient will not be treated with study drug and the choice of the treatment will be up to the physician). Study duration is estimated in 6 years, 1 year of estimated enrollment, 2 years therapy duration. Thereafter, information on course and survival is due for other 3 years. The main data analysis will be performed when all patients will complete 24 months of treatment (or discontinued earlier). Safety and tolerability profile will be assessed by collecting hematologic and non-hematologic adverse events, laboratory examinations and ECG data. The molecular response will be assessed using the GIMEMA standardized molecular laboratories (Labnet network).
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Chronic Myeloid Leukemia
Intervention ICMJE	Drug: Nilotinib; Administered orally at the dose of 300 mg twice daily (total daily dose 600 mg daily) for 24 months (study core), and indefinitely if it is in the interest of the patient (the drug will be given free-of-charge after 24 months to all those patients achieving the CMR4 at 24 months and in absence of safety concerns). Nilotinib dose is increased to 400 mg BID in case of suboptimal response or failure (with the exception of patients who will fail for progression to ABP: in case of progression to ABP, the patient will not be treated with study drug and the choise of the treatment will be up to the physician).
Study Arms	Not Provided
Publications *	Castagnetti F, Breccia M, Gugliotta G, Martino B, D'Adda M, Stagno F, Carella AM, Avanzini P, Tiribelli M, Trabacchi E, Visani G, Gobbi M, Salvucci M, Levato L, Binotto G, Capalbo SF, Bochicchio MT, Soverini S, Cavo M, Martinelli G, Alimena G, Pane F, Saglio G, Rosti G, Baccarani M; GIMEMA CML Working Party. Nilotinib 300 mg twice daily: an academic single-arm study of newly diagnosed chronic phase chronic myeloid leukemia patients. Haematologica. 2016 Oct;101(10):1200-1207. Epub 2016 Jul 28.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Active, not recruiting
Estimated Enrollment ICMJE; (submitted: February 16, 2012)	109
Original Estimated Enrollment ICMJE	Same as current
Estimated Study Completion Date	May 2018
Actual Primary Completion Date	November 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Age ≥ 18; Male or female patients with diagnosis of Ph+ and/or BCR-ABL+ CML; Early chronic phase (within 6 months from diagnosis); Pretreatment with Hydroxyurea or Anagrelide for a duration of up to 3 months and/or pretreatment with Imatinib for up to 30 days are permitted; Normal serum levels of potassium, magnesium, phosphorus, total calcium corrected for serum albumin or phosphorus, or correctable to within normal limits with supplements prior to the first dose of study medication; Written informed consent prior to any study procedures being performed; AST and ALT ≤ 2.5 x ULN or ≤ 5.0 x ULN if considered due to leukaemia; Alkaline phosphatase ≤ 2.5 x ULN unless considered due to leukaemia; Total direct bilirubin ≤ 1.5 x ULN, except know Mb. Gilbert; Serum creatinine ≤ 1.5 x ULN Exclusion Criteria: Known impaired cardiac function, including any of the following:; LVEF < 45%; Complete left bundle branch block; Right bundle branch block plus left anterior hemiblock, bifascicular block; Use of a ventricular-paced pacemaker; Congenital long QT syndrome; History of or presence of clinically significant ventricular or atrial tachyarrhythmias; Clinically significant resting bradycardia (<50 beats per minute); QTc>450 msec on screening ECG. If QTc > 450 msec and electrolytes are not within normal ranges before Nilotinib dosing, electrolytes should be corrected and then the patient rescreened for QTc criterion.; Myocardial infarction within 12 months prior to starting study drugs; Other clinical significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension); Serum lipase and amylase > 1.5 x ULN (upper limit of normal) or history of acute (i.e., within 1 year of starting study medication) or chronic pancreatitis; Other concurrent uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infections, acute or chronic liver and renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol; Impaired gastrointestinal function or disease that may alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting and diarrhea, malabsorption syndrome, small bowel resection or gastric by-pass surgery); Concomitant medications with potential QT prolongation (see link for complete list: http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm); Concomitant medications known to interact with CYP450 isoenzymes (CYP3A4, CYP2C9,andCYP2C8:link for complete list: http://medicine.iupui.edu/flockhart/table.html..; Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy; Patients who are pregnant or breast feeding, or women of reproductive potential not employing an effective method of birth control. (Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to administration of nilotinib).; Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.; Patients unwilling or unable to comply with the protocol
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Italy
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01535391
Other Study ID Numbers ICMJE	CML0811; 2011-002787-25 ( EudraCT Number )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Plan to Share IPD: No
Responsible Party	Gruppo Italiano Malattie EMatologiche dell'Adulto
Study Sponsor ICMJE	Gruppo Italiano Malattie EMatologiche dell'Adulto
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Chair: Gianantonio Rosti Dpt of Hematology and Oncology, "Seràgnoli", Sant'Orsola-Malpighi. University Hospital of Bologna
PRS Account	Gruppo Italiano Malattie EMatologiche dell'Adulto
Verification Date	March 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP