Pre-reinductive Decitabine and Vorinostat in Relapsed Lymphoblastic Lymphoma or Acute Lymphoblastic Leukemia

• Status: Terminated
• Trial end date: 2013-01-01
• Target enrollment: 0
• Participant gender: 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. 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Masonic Cancer Center, University of Minnesota
• Treatments: Asparaginase; Azacitidine; Cytarabine; Decitabine; Doxorubicin; Imatinib Mesylate; Liposomal doxorubicin; Methotrexate; Pegaspargase; Prednisone; Vincristine; Vorinostat

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