Phase I 5-Azacytidine Plus VPA Plus ATRA
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01575691 |
Recruitment Status
:
Completed
First Posted
: April 11, 2012
Last Update Posted
: April 11, 2012
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Myelodysplastic Syndrome Acute Myelogenous Leukemia | Drug: 5-Azacytidine (5-aza) Drug: Valproic Acid Drug: All-Trans Retinoic Acid (ATRA) | Phase 1 |
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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 21 participants |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Study Start Date : | July 2005 |
Actual Primary Completion Date : | July 2007 |
Actual Study Completion Date : | December 2007 |

Arm | Intervention/treatment |
---|---|
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)
Start at 75 mg/m^2 subcutaneously daily for 7 days.
Other Names:
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:
|
- 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.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 3 Years and older (Child, Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01575691
United States, Texas | |
The University of Texas M.D. Anderson Cancer Center | |
Houston, Texas, United States, 77030 |
Principal Investigator: | Guillermo Garcia-Manero, MD | M.D. Anderson Cancer Center |
Additional Information:
Responsible Party: | M.D. Anderson Cancer Center |
ClinicalTrials.gov Identifier: | NCT01575691 History of Changes |
Other Study ID Numbers: |
2004-0799 Phase I |
First Posted: | April 11, 2012 Key Record Dates |
Last Update Posted: | April 11, 2012 |
Last Verified: | April 2012 |
Keywords provided by M.D. Anderson Cancer Center:
All-trans retinoic acid Tretinoin Vesanoid 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 ATRA |
Additional relevant MeSH terms:
Tretinoin Syndrome Leukemia Myelodysplastic Syndromes Preleukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Disease Pathologic Processes Neoplasms by Histologic Type Neoplasms Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Azacitidine |
Valproic Acid Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Enzyme Inhibitors Anticonvulsants GABA Agents Neurotransmitter Agents Physiological Effects of Drugs Antimanic Agents Tranquilizing Agents Central Nervous System Depressants Psychotropic Drugs Keratolytic Agents |