A Multicenter Total Therapy Strategy for De Novo Adult Philadelphia Chromosome Positive (Ph+) Acute Lymphoblastic Leukemia (ALL) Patients. GIMEMA Protocol LAL1509, EudraCT Number 2010-019119-39
- Patients with de novo Ph+ and/or BCR/ABL+ ALL.
- Age ≥18 years old ≤60 years.
- No prior treatment with any anti-leukemic drugs with the exception of steroids for no
more than 14 days (including the 7-day pretreatment already scheduled in the
- WHO performance status ≤2.
- No evidence of central nervous system (CNS) leukemia.
- Normal serum level of potassium, total calcium corrected for serum albumin magnesium
and phosphorus, or correctable with supplements.
- ALT and AST ≤2.5 x ULN or ≤5.0 x ULN if considered due to leukemia.
- Alkaline phosphatase ≤2.5 x ULN unless considered to leukemia.
- Serum bilirubin ≤2 x ULN.
- Serum creatinine ≤3 x ULN.
- Serum amylase ≤1.5 x ULN and serum lipase ≤1.5 x ULN.
- Normal cardiac function.
- Written informed consent prior to any study procedures being performed. In addition,
patients must be thoroughly informed about all aspects of the study, including the
study visit schedule and required evaluations and all regulatory requirements for
- Impaired cardiac function, including any one of the following:
- LVEF <45% as determined by MUGA scan or echocardiogram.
- Complete left bundle branch block.
- Use of a cardiac pacemaker.
- ST depression of >1mm in 2 or more leads and/or T wave inversions in 2 or more
- Congenital long QT syndrome.
- History of or presence of significant ventricular or atrial arrhythmia.
- Clinically significant resting bradycardia (<50 beats per minute).
- QTc >450 msec on screening ECG (using the QTcF formula).
- Right bundle branch block plus left anterior hemiblock, bifascicular block.
- Myocardial infarction within 3 months prior to starting Dasatinib.
- Angina pectoris.
- Other clinically significant heart disease (e.g., congestive heart failure,
uncontrolled hypertension, history of labile hypertension, or history of poor
compliance with an antihypertensive regimen).
- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of Dasatinib (e.g., ulcerative diseases, uncontrolled nausea,
vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
- Use of therapeutic warfarin.
- Acute or chronic liver or renal disease considered unrelated to leukemia.
- Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled
diabetes) that could cause unacceptable safety risks or compromise compliance with
- Active uncontrolled systemic fungal, bacterial, viral, or other infection (defined as
exhibiting ongoing signs/symptoms related to the infection and without improvement,
despite appropriate antibiotics or other treatment).
- Treatment with any hematopoietic colony-stimulating growth factors (e.g., G-CSF,
GMCSF) ≤1 week prior to starting study drug.
- Patients who are currently receiving treatment with any of the medications listed in
"Appendix H" and the treatment cannot be either discontinued or switched to a
different medication prior to starting study drug. The medications listed in
"Appendix H" have the potential to prolong the QT interval.
- Patients who have received any antileukemic agents and treatments including steroids.
for more than 14 days including 7 days pretreatment that is part of the protocol.
- Patients who have received any investigational drug in the last 2 weeks.
- 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 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 administration of Dasatinib.
Post-menopausal women must be amenorrhoeic for at least 12 months to be considered of
non-childbearing potential. Male and female patients must agree to employ an
effective barrier method of birth control throughout the study and for up to 3 months
following discontinuation of study drug.
- Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not
- Patients with a history of another primary malignancy that is currently clinically
significant or currently requires active intervention.
- Non compliant to oral medication patients.
- Significant pleural effusion on baseline chest X-Ray (CXR) or pericardial effusion on
- Use of H2 blockers or proton pump inhibitors.