Study of Hyper-CVAD Plus Imatinib Mesylate for Philadelphia-Positive Acute Lymphocytic Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma
Intervention: Imatinib Mesylate; Cyclophosphamide; Doxorubicin; Vincristine; Dexamethasone; Methotrexate; Cytarabine; Mesna; G-CSF
Intervention description: 600 mg by mouth on days 1 - 14 for course 1, and 600 mg by mouth daily days 1-14 (or daily if tolerated with course 1) for courses 2, 4, 6, 8.; 300 mg/m^2 by vein every 12 hours for 6 doses days 1, 2, 3 (total dose 1800 mg/m^2) for courses 1, 3, 5, 7.; 50 mg/m^2 by vein on day 4 after last dose of CTX for courses 1, 3, 5, 7.; 2 mg by vein on day 4 and day 11 for courses 1, 3, 5, 7.; 40 mg by vein or by mouth daily on days 1 - 4 and days 11 - 14 for courses 1, 3, 5, 7.; 12 mg intrathecally (6 mg if via Ommaya reservoir) day 2 for courses 1, 3, 5, 7.
200 mg/m^2 by vein over 2 hours followed by 800 mg/m^2 over 22 hours on day 1 of courses 2, 4, 6, 8.; 100 mg intrathecally day 7 for courses 1, 3, 5, 7.
3 gm/m2 by vein over 2 hrs every 12 hrs for 4 doses on days 2 and 3 for courses 2, 4, 6, 8.; 600 mg/m^2 by vein daily for 24 hours for courses 1, 3, 5, 7.; 10 mcg/kg/day after completion of chemotherapy until neutrophil recovery to 1 x 109/L or higher for all courses.
Intervention MeSH terms: Cytarabine; Dexamethasone; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine; Imatinib Mesylate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Minimum age: 15 Years
Healthy volunteers: No
Keywords: Leukemia; Lymphoblastic; Acute; Philadelphia-Positive; Imatinib Mesylate; Gleevec; Glivec; Imatinib; STI571; STI-571; CGP-57148B; NSC-716051; Cyclophosphamide; Cytoxan®,; Neosar®; Doxorubicin; Adriamycin ®; Rubex ®; Adriamycin PFS; Adriamycin RDF; Vincristine; Dexamethasone; Decadron; Methotrexate; Cytarabine; Ara-C; Cytosar; DepoCyt; Cytosine Arabinosine Hydrochloride; Mesna; Mesnex; G-CSF; Filgrastim; Neupogen

Summary:

      The goal of this clinical research study is to learn if intensive chemotherapy, combined with
      imatinib mesylate (Gleevec, STI571) given for 8 courses over 6 months, followed by
      maintenance imatinib mesylate plus chemotherapy for 2 years, followed by imatinib mesylate
      indefinitely can improve Philadelphia-positive acute lymphoblastic leukemia. The safety of
      this treatment will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of previously untreated Ph-positive ALL or previously treated in CR after
             1-2 courses of therapy or failure after one course of induction chemotherapy without
             imatinib mesylate.

          2. Age > or = 15 years. Those < 15 years of age will be treated under compassionate IND.

          3. Zubrod performance status < or = 2 (ECOG Scale, Appendix A).

          4. Adequate liver function (bilirubin < or = to 3.0 mg/dl, unless considered due to
             tumor), and renal function (creatinine < or = to 3.0 mg/dl, unless considered due to
             tumor).

          5. Adequate cardiac function as assessed clinically by physical examination.

          6. Signed informed consent.

        Exclusion Criteria:

          1. Active serious infection not controlled by oral or intravenous antibiotics.

          2. Treatment with investigational antileukemic agent or chemotherapy agents in the last 7
             days before study entry, unless full recovery from side-effects has occurred or
             patient has rapidly progressive disease judged life-threatening.

          3. Active secondary malignancy other than skin cancer (e.g. basal cell carcinoma or
             squamous cell carcinoma) than in investigator's opinion will shorten survival to less
             than 1 year.

          4. History of Grade III/IV cardiac problems as defined by the New York Heart Association
             Criteria.

          5. Prior history of treatment with imatinib mesylate.

          6. Pregnancy or lactating in women of childbearing potential.