Phase II Study of Idarubicin, Cytarabine, and Vorinostat in Patients With High-Risk MDS and AML
The Study Drugs:
Vorinostat is designed to change the gene expression profile of leukemia cells, which may
cause the cells to die.
Idarubicin is designed to cause breaks in DNA (the genetic material of cells). This may
cause cancer cells to die.
Ara-C is designed to insert itself into DNA of cancer cells and stop the DNA from repairing
itself.
This dose combination has not been tested in humans before, at this dose level and schedule.
Study Drug Administration:
Induction Therapy:
If you are found to be eligible to take part in this study, you will begin induction
therapy. During induction therapy, the dose level of vorinostat may vary based on when you
join the study and on the side effects seen in other participants. The first group of 3
participants will receive the highest dose level of vorinostat. If intolerable side effects
are experienced, the next group of 3 participants will receive a lower dose of vorinostat.
This will continue until the highest dose of vorinostat with no intolerable side effects is
found. The dose levels of the other drugs will not change.
In the Induction phase, you will receive 1 or 2 induction cycles of therapy on the following
schedule:
- On Days 1-3, you will take vorinostat by mouth 3 times a day.
- On Days 4-6, you will receive idarubicin through a needle in your vein over 1 hour.
- On Days 4-7, you will receive ara-C by vein as a non-stop infusion.
- On Days 4-7, you will receive solumedrol or dexamethasone to help reduce the risk of
side effects associated with ara-C. The drug will be given by vein over a few seconds.
Consolidation Therapy:
If the disease responds during Induction, you may be able to receive up to 5 additional 4-6
week study cycles. During these Consolidation Cycles, you will take the study drugs on the
following cycle:
- On Days 1-3, you will take vorinostat by mouth 3 times a day.
- On Days 4 and 5, you will receive idarubicin through a needle in your vein over 5
minutes.
- On Days 4-6, you will receive ara-C by vein as a non-stop infusion.
- On Days 4 and 5, you will also receive either solumedrol or dexamethasone by vein over
a few seconds.
Maintenance Therapy:
If you go into remission, you will begin maintenance therapy. While on maintenance therapy,
you will take vorinostat by mouth 3 times a day on Days 1-14 of each 28-day study cycle.
You may have up to 12 Maintenance Cycles.
Study Visits:
At least every week during Cycle 1, and then at least once a month during each additional
cycle, blood (about 1-2 teaspoons) will be drawn for routine tests. You will also have
routine bone marrow aspirates and biopsies before initiating treatment and approximately on
Day 21 and Day 28 after initiating therapy.
Length of Study:
You may continue to receive the study drugs for up to 18 cycles. You will be taken off
study early if the disease gets worse or intolerable side effects occur.
This is an investigational study. Idarubicin is FDA approved for use in combination with
other approved drugs for the treatment of AML. Vorinostat is FDA approved and commercially
available for the treatment of some forms of cutaneous lymphoma. Ara-C is FDA approved for
use in the treatment of leukemia. The use of these drugs together is investigational.
Up to 105 patients will take part in this study. All will be enrolled at MD Anderson.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression free survival
7 Months
No
Guillermo Garcia-Manero, M.D.
Study Chair
M.D. Anderson Cancer Center
United States: Institutional Review Board
2007-0835
NCT00656617
April 2008
April 2015
Name | Location |
---|---|
The University of Texas M.D. Anderson Cancer Center | Houston, Texas |