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

Gruppo Italiano Malattie EMatologiche dell'Adulto

Status and phase

Completed

Phase 3

Conditions

Chronic Myeloid Leukemia

Treatments

Drug: Nilotinib

Study type

Interventional

Funder types

Other

Identifiers

NCT01535391

CML0811

2011-002787-25 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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).

Enrollment

109 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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