Treatment of Adult Ph+ LAL With BMS-354825
Condition: Lymphoblastic Leukemia, Acute
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: Dasatinib
Intervention MeSH terms: Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 53.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Ph+ Acute Lymphoblastic Leukaemia; Dasatinib; targeted therapy; Patients with Ph positive and or BCR ABL positive ALL

Summary:

      The primary objective of the trial is to estimate the activity of BMS-354825 (Dasatinib) in
      de novo adult Ph+ ALL patients in terms of hematological complete remission (HCR) rate.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with Ph+ and/or BCR/ABL+ ALL

          -  Age ≥18 years old

          -  De novo ALL (within 14 days from diagnosis)

          -  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 protocol)

          -  WHO performance status ≤2

          -  Absence 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.

        Exclusion Criteria:

          -  Impaired cardiac function, including any one of the following:

          -  Impairment of gastrointestinal (GI) function or GI disease that may significantly
             alter the absorption of BMS-354825 (e.g., ulcerative diseases, uncontrolled nausea,
             vomiting, diarrhoea, 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, active or uncontrolled infection) that could cause unacceptable safety risks
             or compromise compliance with the protocol

          -  Treatment with any hematopoietic colony-stimulating growth factors (e.g., G-CSF,
             GM¬CSF) ≤1 week prior to starting study drug

          -  Patients who are currently receiving treatment with any of the medications listed in
             "Appendix F" and the treatment cannot be either discontinued or switched to a
             different medication prior to starting study drug. The medications listed in "Appendix
             F" have the potential to prolong the QT interval.

          -  Patients who have received any anti-leukemic 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 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 administration of
             BMS-354825). Post-menopausal women must be amenorrheic 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
             mandatory)

          -  Patients with a history of another primary malignancy that is currently clinically
             significant or currently requires active intervention

          -  Non compliant to oral medication patients.