Pegaspargase and Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: cyclophosphamide; cytarabine; dexamethasone; doxorubicin hydrochloride; imatinib mesylate; methotrexate; methylprednisolone; pegaspargase; vincristine sulfate
Intervention description: Day 1- 3: 300 m g/m2 IV over 2-3 hours every 12 hours for 6 doses plus mesna 600 mg/ m2 /day continuous infusion Days 1-3; Day 2 & 3: 3g/m2 IV over 2 hours q12 X 4; Day 1-4; 11-14: 40 mg daily; Day 4: 50 mg/m2 IV over 2 hours; 600 mg/day; Day 1: 1g/ m2 (200 mg/ m2load IV over 2 hours plus 800 mg/ m2 over 22 hours as an infusion; Day 1-3: 50mg IV BID; Day 3/Day4: 2,500 IU/ m2 IV; Day 4 & 11: 2 mg IV
Intervention MeSH terms: Cytarabine; Dexamethasone; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine; Imatinib Mesylate; Asparaginase; Pegaspargase
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: adults; Philadelphia chromosome precursor ALL,; T-cell ALL; untreated ALL

Summary:

      RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer
      cells, either by killing the cells or by stopping them from dividing. Giving more than one
      drug (combination chemotherapy) may kill more cancer cells.

      PURPOSE: This phase II trial is studying the side effects of giving pegaspargase together
      with combination chemotherapy and to see how well it works in treating patients with newly
      diagnosed acute lymphoblastic leukemia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must be newly diagnosed (untreated) with Acute Lymphoblastic Leukemia based
             on a bone marrow examination unless there is a contraindication to having the test
             performed. This includes precursor-B ALL, precursor-T ALL, and Philadelphia chromosome
             positive ALL. For reference, see criteria by Center for International Blood and Marrow
             Transplant Research (CIBMTR).> 20% blasts on a bone marrow aspirate OR If a bone
             marrow aspirate is not obtained, the diagnosis of acute leukemia can be established by
             a pathologic diagnosis of acute leukemia on a bone marrow biopsy OR A complete blood
             count documenting the presence of at least 10,000 white blood cells (WBC)/μl and at
             least 20% circulating blasts

          -  Adults, 18 to 60 years of age.

          -  Women of child bearing potential (WOCBP) must be willing to use adequate contraception
             to avoid pregnancy for the duration of study participation.

          -  Eastern Cooperative Oncology Group (ECOG) performance status < 2

          -  Adequate renal function defined as: Serum creatinine ≤ 2.0 x upper limit normal (ULN)
             for institution

          -  Adequate hepatic function defined as:Total bilirubin ≤ 2.0 x ULN for institution
             Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.0 x ULN for
             institution

          -  Patient must have the ability to understand and the willingness to sign a written
             informed consent document. The patient and/or the patient's legally authorized
             guardian must acknowledge consent for treatment as a human subject on this study.

        Exclusion Criteria:

          -  Mature B (Burkitt's) ALL will be excluded.

          -  An active malignancy other than ALL (with the exception of basal and/or squamous cell
             skin cancers and curatively treated carcinoma of the cervix) within 5 past years of
             study entry.

          -  Documented central nervous system (CNS) involvement with leukemia will be excluded. A
             diagnostic lumbar puncture will not be part of screening procedures.

          -  Severe pulmonary, renal, or hepatic disease not related to the patient's ALL will be
             excluded.

          -  Cardiac dysfunction as defined by:Myocardial infarction within the last 6 months of
             study entry, or Reduced left ventricular function with an ejection fraction ≤50% as
             measured by Multigated Acquisition (MUGA) scan or echocardiogram at study entry,
             Unstable angina, Unstable cardiac arrhythmias, New York Heart Association (NYHA) Class
             III or IV heart failure, Electrocardiographic evidence of acute ischemia or active
             conduction system abnormalities

          -  Known or suspected human immunodeficiency virus (HIV)-positive patients are excluded
             from the study because of possible risk of lethal infection when treated with marrow
             suppressive therapy.

          -  Any concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled
             diabetes, infection, hypertension, etc.) or psychiatric illness that could, in the
             investigator's opinion, potentially interfere with the completion of treatment
             according to this protocol.

          -  Patients who have had chemotherapy or radiotherapy for ALL prior to entering the study
             will be excluded. Hydroxyurea and one dose of intravenous vincristine are allowed
             prior to registration for patient convenience. Prior steroid therapy is allowable, ≤5
             days prior to the start of the regimen.

          -  Patients may not have received any other investigational agents within the last 30
             days.

          -  WOCBP who are unwilling or unable to use an acceptable method of contraception for the
             entire study period. Pregnant or lactating women are excluded from this study because
             of possible risk to the fetus or infant. Women with a positive serum pregnancy test on
             enrollment or prior to study drug administration will be excluded.

          -  Men whose sexual partners are WOCBP, who are unwilling or unable to use an acceptable
             contraceptive method to avoid pregnancy of his partner for the entire study period.