Pre-reinductive Decitabine and Vorinostat in Relapsed Lymphoblastic Lymphoma or Acute Lymphoblastic Leukemia
|ClinicalTrials.gov Identifier: NCT00882206|
Recruitment Status : Terminated (Slow accrual)
First Posted : April 16, 2009
Results First Posted : October 28, 2016
Last Update Posted : December 28, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia Lymphoma||Drug: cytarabine Drug: decitabine Drug: doxorubicin hydrochloride Drug: imatinib mesylate Drug: methotrexate Drug: pegaspargase Drug: prednisone Drug: vincristine sulfate Drug: vorinostat||Phase 2|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Therapeutic Trial of Decitabine and Vorinostat in Combination With Chemotherapy (Vincristine, Prednisone, Doxorubicin and PEG-Asparaginase) for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LL)|
|Study Start Date :||April 2009|
|Actual Primary Completion Date :||January 2013|
|Actual Study Completion Date :||January 2013|
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)
- Response to Treatment [ Time Frame: Day 33 ]Response includes both complete remission (defined as <5% leukemic blasts in the bone marrow) and partial remission (defined as a greater than 35% reduction in the bone marrow leukemia blast percentage at day 33)
- Level of Methylation [ Time Frame: Day 0 ]the percentage of methylated DNA
- Level of Methylation [ Time Frame: Day 5 ]the percentage of methylated DNA
- Level of Methylation [ Time Frame: Day 33 ]the percentage of methylated DNA
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|