A Phase 2 Trial of Vorinostat in Combination with Azacitidine in Patients with Newly-Diagnosed Acute Myelogenous Leukemia or Myelodysplastic Syndrome who are ineligible for other Leukemia Protocols
The goal of this clinical research study is to learn if the combination of azacitidine and vorinostat can help to control AML or MDS better than azacitidine alone. The safety of this drug combination will also be studied.
Disease Group: Leukemia
Treatment Agent: Azacitidine
Treatment Location: Both at MD Anderson & outside MD Anderson at one or more Collaborating Sites or Institutions
Estimatated Length of Stay in Houston: N/A
Sponsor: Merck and Co.
Return Visit: Courses will be repeated every 3 to 8 weeks.
Home Care: N/A
Primary: To 1) determine the effect of vorinostat in combination with 5-azacitidine versus 5-azacitidine alone on the 60 day survival of patients with untreated AML or MDS (Intermediate-1 or higher risk) who are ineligible for frontline studies and 2) the clinical activity of this combination in the above specified patient population. Secondary: To evaluate the safety and tolerability of this combination on this patient population, and the study the in vivo effect of this combination on methylation/acetylation status.
IRB Review and Approval Date: 09/08/2009
Recruitment Status: Closed
Projected Accrual: 110
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.
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.