A Pilot Study of Decitabine and Vorinostat With Chemotherapy for Relapsed ALL
This is a pilot study using decitabine and vorinostat before and during chemotherapy with vincristine, dexamethasone, mitoxantrone, and peg-asparaginase in pediatric patients with acute lymphoblastic leukemia (ALL).
Acute Lymphoblastic Leukemia
Precursor B-Cell Lymphoblastic Leukemia
Precursor T-Cell Lymphoblastic Leukemia
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of Decitabine and Vorinostat With Chemotherapy for Relapsed ALL|
- Number of participants with adverse events. [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]To evaluate the side effects of giving decitabine and vorinostat before and during chemotherapy using the standard drugs vincristine, dexamethasone, PEG-asparaginase and mitoxantrone.
- Disease response rate after treatment. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]The study will assess whether the patient's acute lymphoblastic leukemia goes into remission after treatment.
- Gene-specific methylation profiles [ Time Frame: 2 years ] [ Designated as safety issue: No ]To assess the biologic activity of decitabine by comparing pre and post-treatment marrow samples for global and gene-specific methylation profiles using HELP and methylation-specific PCR.
- Global histone acetylation and histone modifications [ Time Frame: 2 years ] [ Designated as safety issue: No ]To assess the biological activity of vorinostat by comparing pre- and post-treatment blood and bone marrow samples for global histone acetylation (using acetyl-H3 Western blotting), and for gene-specific histone modifications (using H3K9/14Ac ChIP-chip and ChIP-qPCR).
- Gene expression profiles [ Time Frame: 2 years ] [ Designated as safety issue: No ]To determine the impact of combined epigenetic therapy on the expression of epigenetically-regulated genes by comparing pre and post-treatment marrow samples for gene expression profiles (using microarrays), and correlating these with the methylation and histone modification assays.
|Study Start Date:||December 2011|
|Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
- suberoylanilide hydroxamic acid (SAHA)
- Vincasar PFS
- vincristine sulfate
- Dexamethasone Intensol
- dexamethasone acetate
- dexamethasone sodium phosphate
- 8 mg for patients age 1-1.99
- 10 mg for patients age 2-2.99
- 12 mg for patients 3-8.99 years of age
- 15 mg for patients >9 years of age
Given intrathecally to all patients the dose defined by age below.
CNS 1 or 2 patients get doses on day 8, 22 and 35 and CNS 3 patients should get doses on day 8, 15, 22, 29 and 35
Decitabine is a demethylating agent and vorinostat is a HDAC inhibitor. The use of demethylating agents and HDAC inhibitors in combination have been previously shown to have synergistic effects in altering neoplastic pathways of cancer cells and be well tolerated in human clinical studies. With the ability of decitabine and vorinostat to alter the abnormal cellular pathways of leukemic blasts and essentially turn off anti-apoptotic proteins, the leukemia cells have become primed for cytotoxic cell kill via chemotherapeutic agents. This study will ask the question as to whether or not the combination of decitabine and vorinostat followed by chemotherapy is feasible and whether it can positively impact outcome in patients with relapsed or refractory acute lymphoblastic leukemia.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01483690
Show 28 Study Locations
|Study Chair:||Michael Burke, MD||University of Minnesota Children's Hospital|