Clinical trial NCT00656617
Conditions: Acute Myeloid Leukemia (AML) Myelodysplastic Syndrome (MDS)
Keywords: Acute Myeloid Leukemia (AML) Myelodysplastic syndrome (MDS) Leukemia Idarubicin Cytarabine Vorinostat Ara-C
Sponsor: M.D. Anderson Cancer Center
Start date: 2008-04-01; Completion date: 2014-02-01
Enrollment: 106 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The goal of this clinical research study is to find the highest safe dose of vorinostat that can be given in combination with idarubicin and ara-C for the treatment of AML and high-risk MDS.

Once the highest safe dose is found, researchers will then try to learn if this combination treatment can help to control AML and high-risk MDS in newly diagnosed patients. The safety of this treatment combination will also be studied.

Detailed description:
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.

Arms: arm 1: Idarubicin 12 mg/m\^2 by vein (IV) over 1 hour daily for 3 days (days 4 to 6). Ara-C (Cytarabine) 1.5 g/m\^2 IV as a continuous infusion over 24 hours daily (days 4 to 7). Vorinostat initial dose level 500 mg orally three times a day for 3 days (days 1 to 3).
Interventions: intervention 1: Idarubicin intervention 2: Cytarabine intervention 3: Vorinostat
Intervention descriptions: intervention 1: 12 mg/m\^2 IV over 1 hour daily for 3 days (days 4 to 6) intervention 2: 1.5 g/m\^2 IV as a continuous infusion over 24 hours daily (days 4 to 7) intervention 3: Initial dose level 500 mg orally three times a day for 3 days (days 1 to 3).

Protocol documents: