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Phase I Study of the Combination of 5-azacytidine With Valproic Acid and All-trans Retinoic Acid in Patients With High Risk Myelodysplastic Syndrome and Acute Myelogenous Leukemia

Phase 1
3 Years
Not Enrolling
Myelodysplastic Syndrome, Acute Myelogenous Leukemia

Thank you

Trial Information

Phase I Study of the Combination of 5-azacytidine With Valproic Acid and All-trans Retinoic Acid in Patients With High Risk Myelodysplastic Syndrome and Acute Myelogenous Leukemia

Participants receive 5-aza as an injection under the skin once a day for 7 days. This will
be repeated every 3-8 weeks depending on blood counts and how well bone marrow is
recovering. This is defined as 1 treatment cycle. Also during each cycle, participant will
take VPA by mouth for 7 days and ATRA by mouth for 5 days. VPA will be given on the same
days as 5-aza. ATRA will start on Day 3.

In the Phase I portion of the study, the dose of VPA will be increased in each new group of
participants until the highest safe dose is found. A minimum of 3 participants and a maximum
of 10 will be treated at each dose level.

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)

- 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 * Upper Limits of Normal
(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

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

- 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.

Type of Study:


Study Design:

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

Outcome Measure:

Maximal tolerated dose (MTD) of valproic acid (VPA) in combination with 5-azacytidine (5-aza) and all-trans retinoic acid (ATRA)

Outcome Description:

MTD defined as the dose level below where either 0 dose limiting toxicities (DLTs) out of the first 3 participants, or 1 DLT in the first 3 participants, and 0 DLTs in following additional 3 participants of a cohort. The MTD designation will apply to cycle 1 (28 day cycle). Routine blood tests (about 1-2 teaspoons each time) 2-3 times a week.

Outcome Time Frame:

28 day cycle

Safety Issue:


Principal Investigator

Guillermo Garcia-Manero, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Institutional Review Board

Study ID:

2004-0799 Phase I



Start Date:

July 2005

Completion Date:

December 2007

Related Keywords:

  • Myelodysplastic Syndrome
  • Acute Myelogenous Leukemia
  • Combination Chemotherapy
  • MDS
  • High-Risk Myelodysplastic Syndrome
  • AML
  • Acute myelogenous leukemia
  • valproic acid
  • VPA
  • Depakene
  • 5-azacytidine
  • 5-aza
  • Azacitidine
  • 5-AZC
  • Vidaza
  • AZA-CR
  • Ladakamycin
  • NSC-102816
  • All-trans retinoic acid
  • ATRA
  • Tretinoin
  • Vesanoid
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia



The University of Texas M.D. Anderson Cancer Center Houston, Texas