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Phase I 5-Azacytidine Plus VPA Plus ATRA

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ClinicalTrials.gov Identifier: NCT01575691
Recruitment Status : Completed
First Posted : April 11, 2012
Last Update Posted : April 11, 2012
Celgene Corporation
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

April 9, 2012
April 11, 2012
April 11, 2012
July 2005
July 2007   (Final data collection date for primary outcome measure)
Maximal tolerated dose (MTD) of valproic acid (VPA) in combination with 5-azacytidine (5-aza) and all-trans retinoic acid (ATRA) [ Time Frame: 28 day cycle ]
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.
Same as current
No Changes Posted
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Phase I 5-Azacytidine Plus VPA Plus ATRA
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
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.

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.

Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Myelodysplastic Syndrome
  • Acute Myelogenous Leukemia
  • Drug: 5-Azacytidine (5-aza)
    Start at 75 mg/m^2 subcutaneously daily for 7 days.
    Other Names:
    • Azacitidine
    • 5-azacytidine
    • 5-AZC
    • Vidaza
    • AZA-CR
    • Ladakamycin
    • NSC-102816
  • Drug: Valproic Acid
    50 mg/kg daily by mouth for 7 days, same days as 5-aza.
    Other Name: Depakene
  • Drug: All-Trans Retinoic Acid (ATRA)
    45 mg/m^2 orally daily (in two divided doses) for 5 days starting on day 3 of the administration of 5-aza and VPA.
    Other Names:
    • Tretinoin (oral)
    • Vesanoid
Experimental: VPA + 5-aza + ATRA
Daily for 7 days, Valproic acid (VPA) starting dose 75 mg/m^2 subcutaneously in combination with 5-azacytidine (5-aza) 50 mg/kg orally; and all-trans retinoic acid (ATRA) 45 mg/m^2 orally daily (in two divided doses) for 5 days starting on day 3.
  • Drug: 5-Azacytidine (5-aza)
  • Drug: Valproic Acid
  • Drug: All-Trans Retinoic Acid (ATRA)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
December 2007
July 2007   (Final data collection date for primary outcome measure)

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 * 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 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.
Sexes Eligible for Study: All
3 Years and older   (Child, Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
2004-0799 Phase I
Not Provided
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M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
Celgene Corporation
Principal Investigator: Guillermo Garcia-Manero, MD M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
April 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP