Decitabine, Vorinostat, and Combination Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma That Has Relapsed or Not Responded to Treatment
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.
Drug: doxorubicin hydrochloride
Drug: imatinib mesylate
Drug: vincristine sulfate
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Therapeutic Trial of Decitabine (Dacogen) and Vorinostat (SAHA) in Combination With Chemotherapy (Vincristine, Prednisone, Doxorubicin and PEG-Asparaginase) for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LL) MT2008-29R|
- Response to Treatment [ Time Frame: Day 33 or Day 42 ] [ Designated as safety issue: No ]as measured by remission rate at day 33 (< 5% blasts) or day 42 per RECIST criteria
- Toxicity as measured by NCI CTCAE v3.0 [ Time Frame: From 1st Dose to 30 Days Post Treatment ] [ Designated as safety issue: Yes ]Measured by the National Cancer Institute's Common Toxicity Criteria for Adverse Events
- pharmacodynamic effects of decitabine and vorinostat [ Time Frame: Baseline, Day 5 and End of Treatment ] [ Designated as safety issue: No ]Biological correlative endpoints will be met through the analysis of bone marrow and blood samples collected at baseline, day 5 and at the end of treatment - will include LINE methylation analysis of the leukemia cells to determine the methylation status of these relapsed/refractory leukemia/lymphomas prior to study therapy along with the impact of demethylating/HDAC inhibitor agents in these patients.
|Study Start Date:||April 2009|
|Study Completion Date:||January 2013|
|Primary Completion Date:||January 2013 (Final data collection date for primary outcome measure)|
Experimental: Decitabine / Vorinostat
This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
At baseline when peripheral blood draw and bone marrow aspirate performed.
*Intrathecal Cytarabine administered dependent upon age - ranging from 30 mg to 70 mg.
Other Name: cytosine arabinosideDrug: decitabine
Days 1-4, 15 mg/m^2 intravenously (IV) over 1 hour
Other Name: Dacogen(R)Drug: doxorubicin hydrochloride
Day 5, 60 mg/m^2 intravenously (IV) over 15 minutes
Other Name: DoxorubicinDrug: imatinib mesylate
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.
Other Name: Gleevec(R)Drug: methotrexate
**Intrathecal Methotrexate administered dependent upon age - ranging from 8 mg to 15 mg.
Other Name: MTXDrug: pegaspargase
2,500 IU/m2 IM or IV q week (days 6, 12, 19, 26)
Other Name: PEG asparaginaseDrug: prednisone
40mg/m2/day divided BID (days 5 - 33)Drug: vincristine sulfate
1.5mg/m2 (max 2 mg) iv push q week (days 5, 12, 19, 26)
Other Name: Oncovin(R)Drug: vorinostat
Days 1-4, (230 mg/m2)orally divided twice a day (max dose 400 mg daily)
Other Name: suberoylanilide hydroxamic acid (SAHA)
- Patients undergo blood and bone marrow sample collection at baseline, on day 5, Day 19 and at the end of study treatment for correlative laboratory studies. Samples are analyzed for hypermethylation at diagnosis and demethylation post-exposure with decitabine and vorinostat using LINE methylation.
Patients receive decitabine IV over 1 hour and oral vorinostat twice daily on days 1-4; vincristine sulfate IV on days 5, 12, 19, and 26; oral prednisone twice daily on days 5-33; doxorubicin hydrochloride IV over 15 minutes and cytarabine intrathecally (IT) on day 5; pegaspargase IV or intramuscularly on days 6, 12, 19, and 26; and methotrexate* IT on days 12 and 33. Patients with Philadelphia chromosome-positive disease may also receive oral imatinib mesylate once daily on days 5-33.
NOTE: *Patients with central nervous system (CNS)-positive disease also receive methotrexate IT on days 19 and 26.
Patients undergo blood and bone marrow sample collection at baseline, on day 5, Day 19 and at the end of study treatment for correlative laboratory studies.
After completion of study treatment, patients are followed for 60 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00882206
|United States, Minnesota|
|University of Minnesota Amplatz Children's Hospital|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Michael J. Burke, MD||Masonic Cancer Center, University of Minnesota|