Phase II 5-Azacytidine Plus VPA Plus ATRA

• Status: Completed
• Trial end date: 2007-12-01
• Target enrollment: 0
• Participant gender: All

Summary

5-aza is a chemotherapy drug with activity in leukemia and myelodysplastic syndromes (MDS). Researchers hope that valproic acid (VPA) and all-trans retinoic acid (ATRA)will increase the effects of 5-aza. The goal of this clinical research study is to find the highest safe dose of valproic acid (VPA) that can be given in combination with 5-azacytidine (5-aza) and all-trans retinoic acid (ATRA) in the treatment of AML and MDS. The safety and effectiveness of this combination therapy will also be studied.

Additional blood and bone marrow samples will be requested. These samples will be used to evaluate the effect of the treatment on leukemic cells. In addition, any leftover blood and bone marrow samples that are collected at the start of the study and during the regularly scheduled evaluations to be sent for research studies. The research studies will examine changes in the blood and bone marrow cells that might help explain the causes of leukemia and MDS and how the combination of 5-aza, VPA, and ATRA works.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: Celgene Corporation
• Treatments: Azacitidine; Tretinoin; Valproic Acid

Criteria

Inclusion Criteria:

• Patients with refractory or relapsed: acute myelogenous leukemia (AML), and myelodysplastic syndrome (MDS) (bone marrow blasts > or = 10%) are eligible.

• Untreated patients older than 60 years of age with AML or MDS (bone marrow blasts > or = 10%) who refuse or are not eligible for front-line chemotherapy, are eligible.

• Performance status of < or = 2 by the Eastern Cooperative Oncology Group (ECOG) scale.

• Signed informed consent indicating that patients are aware of the investigational nature of this study in keeping with the policies of University of Texas M D Anderson Cancer Center (UTMDACC).

• Age > 2 years. Valproic acid has been associated with a higher rate of severe liver toxicity in children younger than 2 years.

• Patients must have been off chemotherapy for 2 weeks prior to entering this study and recovered from the toxic effects of that therapy, unless there is evidence of rapidly progressive disease. Use of hydroxyurea for patients with rapidly proliferative disease is allowed for the first two weeks on therapy.

• Adequate liver function (bilirubin of < 2mg/dL, SGPT < 3 * ULN) and renal function (creatinine < 2mg/dL).

• Women of childbearing potential must practice contraception. Men and women must continue birth control for the duration of the trial.

• Patients with relapsed /refractory disease with inv16, t(8;21) or t(15;17) are eligible.

Exclusion Criteria:

• Nursing and pregnant females are excluded.

• Patients with active and uncontrolled infections are excluded.

• Patients already receiving valproic acid or receiving other anticonvulsants will be excluded.

• Untreated patients younger than 60 years will not be candidates for this study.

• Patients with untreated disease inv16, t(8;21) or t(15;17) will be excluded.