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A Phase 2 Trial of Vorinostat in Combination With Azacitidine in Patients With Newly-Diagnosed Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS) Who Are Ineligible for Other Leukemia Protocols


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Leukemia

Thank you

Trial Information

A Phase 2 Trial of Vorinostat in Combination With Azacitidine in Patients With Newly-Diagnosed Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS) Who Are Ineligible for Other Leukemia Protocols


The Study Drugs:

Azacitidine is designed to block certain genes in cancer cells whose job is to stop the
function of the tumor-fighting genes. By blocking the "bad" genes, the tumor-fighting genes
may be able to work better.

Vorinostat is designed to cause chemical changes in different groups of proteins that are
attached to DNA (the genetic material of cells), which may slow the growth of cancer cells
or cause the cancer cells to die.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned
(as in the flip of a coin) to 1 of 2 groups.

- If you are in Group 1, you will receive azacitidine and vorinostat.

- If you are in Group 2, you will receive azacitidine alone.

For the first 40 patients, you will have an equal chance of being in either group. After the
first 40 patients, you will have a higher chance of being assigned to a group based on the
results from previous participants.

Study Drug Administration:

On Days 1-5 of every cycle, you will receive azacitidine by vein over 15-30 minutes.

If you are in Group 1, you will also take vorinostat by mouth 3 times a day with food on
Days 1-5 of every cycle.

If you cannot take vorinostat by mouth during a cycle, you will receive only azacitidine
during that cycle. You will begin taking vorinostat by mouth again when you are able.

Your dose of study drugs may be lowered if you experience side effects.

You may receive a drug such as ondansetron before each dose of azacitidine to prevent nausea
and vomiting.

If you have diarrhea, you will take a drug such as Imodium (loperamide) to prevent diarrhea.

Study Visits:

Once a week of Cycle 1, the following tests and procedures will be performed:

- Your complete medical history will be recorded.

- You will have a physical exam.

- You will be asked if you have experienced any intolerable side effects.

- Blood (about 1-2 tablespoons) will be drawn for routine tests.

On Day 28 of Cycle 1 (+/- 3 days), you will have bone marrow aspiration to check the status
of the disease. To collect a bone marrow aspirate, an area of the hip is numbed with
anesthetic, and a small amount of bone marrow is withdrawn through a large needle.

If the doctor thinks it is needed, you will have extra bone marrow aspirations during the
later cycles to check the status of the disease.

One (1) time each cycle of Cycles 2 and beyond, the following tests and procedures will be
performed:

- Your complete medical history will be recorded.

- You will have a physical exam.

- You will be asked if you have experienced any intolerable side effects.

- If the doctor thinks it is needed, blood (about 2 tablespoons) will be drawn for
routine tests.

Length of Study:

You will be on active study for up to 12 cycles (about 12-18 months). You will be taken off
study if the disease gets worse or you experience intolerable side effects.

This is an investigational study. Vorinostat is FDA approved and commercially available for
the treatment of cutaneous T-cell lymphoma. Azacitidine is FDA approved commercially
available for the treatment of MDS. The combination of these drugs for use in patients with
intermediate-1 or higher risk MDS and AML is investigational.

Up to 80 participants will take part in this study. All will be enrolled at MD Anderson.


Inclusion Criteria:



1. Patients with newly diagnosed AML or MDS (Intermediate 1 or higher risk)

2. Patient must have at least one of the following: a. Creatinine >/= 2 mg/dL; b. total
Bilirubin >/= 2 mg/dL; c.ECOG Performance Status equal to 3 or 4; and d. is
ineligible for participation on a protocol of higher priority

3. Patients must provide written informed consent.

4. Patients must be age > 18 years due to lack of safety information with these agents
in children.

5. Patient agrees to: 1) Use 2 adequate methods of contraception to prevent pregnancy
(either 2 barrier methods or a barrier method plus a hormonal contraceptive method)
or 2) abstain from heterosexual activity throughout the study starting with Visit 1.

6. Female patients of childbearing potential should have a negative pregnancy test
(serum) within 72 hrs. of study enrollment.

Exclusion Criteria:

1. Patients must not have the favorable cytogenetic abnormalities of inv (16), t
(16;16), t (8;21), or t (15;17).

2. Patients receiving any anti-leukemic therapy with the exception of Hydroxyurea prior
to study enrollment. Prior growth factor therapy is acceptable. Hydroxyurea could be
used at the discretion of the treating physician. A single or a two day dose of
cytarabine (up to 3 g/m^2) for emergency use is allowed as prior therapy.

3. Patient has a prior history of treatment with HDAC inhibitors. Patients who have
received valproic acid (VPA) for the treatment of seizures may be enrolled on this
study, but must not have received VPA within 30 days of study enrollment.

4. Patient is unable to take and/or tolerate oral medications on a continuous basis,
examples include patients on a ventilator, or have altered mental status that
precludes safe oral route of administration.

5. Patient has active hepatitis A, B, or C infection.

6. Patient is pregnant or breast-feeding.

7. Patient has a known allergy or hypersensitivity to any component of vorinostat or
azacitidine.

8. History of any psychiatric condition that might impair the patient's ability to
understand or to comply with the requirements of the study or to provide informed
consent.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response Rate

Outcome Time Frame:

12-18 Months

Safety Issue:

No

Principal Investigator

Guillermo Garcia-Manero, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2007-0685

NCT ID:

NCT00948064

Start Date:

August 2009

Completion Date:

Related Keywords:

  • Leukemia
  • Leukemia
  • Acute Myelogenous Leukemia
  • AML
  • Myelodysplastic Syndrome
  • MDS
  • Vorinostat
  • SAHA
  • Suberoylanilide Hydroxamic Acid
  • MSK-390
  • Zolinza
  • Azacitidine
  • 5-Azacitidine
  • 5-Aza
  • Vidaza
  • 5-AZC
  • AZA-CR
  • Ladakamycin
  • NSC-102816
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

UT MD Anderson CancerHouston, Texas  77030