Pre-reinductive Decitabine and Vorinostat in Relapsed Lymphoblastic Lymphoma or Acute Lymphoblastic Leukemia
Condition: Leukemia; Lymphoma
MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: cytarabine; decitabine; doxorubicin hydrochloride; imatinib mesylate; methotrexate; pegaspargase; prednisone; vincristine sulfate; vorinostat
Intervention description: At baseline when peripheral blood draw and bone marrow aspirate performed.
*Intrathecal Cytarabine administered dependent upon age - ranging from 30 mg to 70 mg.; Days 1-4, 15 mg/m^2 intravenously (IV) over 1 hour; Day 5, 60 mg/m^2 intravenously (IV) over 15 minutes; 340 mg/m2 by mouth every day (rounded to the nearest 100 mg) for age <18 years and 400 mg orally every day for >18 years on Days 5-33.; **Intrathecal Methotrexate administered dependent upon age - ranging from 8 mg to 15 mg.; 2,500 IU/m2 IM or IV q week (days 6, 12, 19, 26); 40mg/m2/day divided BID (days 5 - 33); 1.5mg/m2 (max 2 mg) iv push q week (days 5, 12, 19, 26); Days 1-4, (230 mg/m2)orally divided twice a day (max dose 400 mg daily)
Intervention MeSH terms: Cytarabine; Prednisone; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine; Imatinib Mesylate; Decitabine; Asparaginase; Vorinostat; Pegaspargase
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 2 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: recurrent adult lymphoblastic lymphoma; recurrent childhood lymphoblastic lymphoma; recurrent adult acute lymphoblastic leukemia; recurrent childhood acute lymphoblastic leukemia

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. Decitabine and
      vorinostat may alter the cancer cells by reversing the cancer pathways needed for cell
      growth. Giving more than one drug (combination chemotherapy) together with decitabine and
      vorinostat may kill more cancer cells than with chemotherapy alone.

      PURPOSE: This phase II trial is studying how well giving decitabine and vorinostat together
      with combination chemotherapy works in treating patients with acute lymphoblastic leukemia or
      lymphoblastic lymphoma that has relapsed or not responded to treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of lymphoblastic lymphoma or acute lymphoblastic leukemia with ≥ 5% blasts
             in the bone marrow (M2/M3) (with or without extramedullary disease) that meets 1 of
             the following criteria:

               -  Refractory disease/induction failure (failure to achieve initial remission after
                  2 lines of induction therapy)

               -  Relapsed disease (in first relapse or higher)

          -  Central nervous system (CNS)-positive disease allowed

          -  Karnofsky performance status (PS) 50-100% (for patients ≥ 16 years of age) OR Lansky
             PS 50-100% (for patients < 16 years of age)

          -  Life expectancy ≥ 8 weeks

          -  Creatinine clearance ≥ 70 mL/min OR maximum serum creatinine based on age/gender as
             follows:

               -  0.4 mg/dL (for patients 1 to 5 months of age)

               -  0.5 mg/dL (for patients 6 to 11 months of age)

               -  0.6 mg/dL (for patients 1 year of age)

               -  0.8 mg/dL (for patients 2 to 5 years of age)

               -  1.0 mg/dL (for patients 6 to 9 years of age)

               -  1.2 mg/dL (for patients 10 to 12 years of age)

               -  1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)

               -  1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients ≥ 16 years of age)

          -  ALT < 5 times upper limit of normal (ULN)

          -  Total bilirubin ≤ 1.5 times ULN for age

          -  LVEF ≥ 40% by ECHO/MUGA scan

          -  Shortening fraction > 29% by ECHO/MUGA scan

          -  Able to swallow capsules

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for 2 months after
             completion of study treatment

          -  No untreated positive blood cultures or progressive infections as assessed by
             radiographic studies

          -  No known allergy to any of the agents or their ingredients used in this study

               -  Patients with clinically significant prior allergies to pegaspargase may be
                  treated with asparaginase-Erwinia, if available

          -  Patients who cannot receive asparaginase on this study (e.g., due to prior
             pancreatitis, stroke, or other toxicity) are eligible provided they meet all other
             inclusion/exclusion criteria

          -  Recovered from prior therapy (defined as CTCAE v3.0 toxicity ≤ grade 1)

          -  More than 3 weeks since prior chemotherapy for cancer other than hydroxyurea for
             patients with WBC > 10,000/mm³

          -  At least 7 days since prior hematopoietic growth factors (14 days for pegfilgrastim)

          -  At least 1 month since prior biologic therapy, such as monoclonal antibodies

          -  At least 3 months since prior hematopoietic stem cell transplantation

        Exclusion Criteria:

          -  Evidence of graft-versus-host disease

          -  Concurrent valproic acid

          -  Concurrent coumadin/warfarin other than a short course administered in a prophylactic
             setting