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A Randomized Phase II Study of the Combination of 5-Azacytidine With Valproic Acid (VPA) Versus Low-Dose Ara-C in Patients With AML/MDS Not Eligible for Other Studies

Phase 2
60 Years
Not Enrolling
Acute Myelogenous Leukemia, Myelodysplastic Syndrome, Leukemia

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Trial Information

A Randomized Phase II Study of the Combination of 5-Azacytidine With Valproic Acid (VPA) Versus Low-Dose Ara-C in Patients With AML/MDS Not Eligible for Other Studies

5-aza is a chemotherapy drug with activity in leukemia and MDS. Researchers hope that VPA
will increase the effects of 5-aza. Low-dose Cytarabine (ara-C) is considered the standard
of care for the treatment of leukemia and MDS in older patients not eligible for other

Before you can start treatment on this study, you will have what are called "screening
tests." These tests will help the doctor decide if you are eligible to take part in the
study. You will have blood drawn (about 2 teaspoons) for routine tests. You will also have
a bone marrow biopsy and aspiration performed. To collect a bone marrow biopsy/aspirate, an
area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow
and bone is withdrawn through a large needle. Women who are able to have children must have
a negative blood or urine pregnancy test.

If you are found to be eligible to take part in this study, you will be randomly assigned
(as in the toss of a coin) to one of two treatment groups. Participants in one group will
receive 5-aza and VPA. Participants in the other group will receive ara-C alone. At first,
there will be an equal chance of being assigned to either group. As the study goes along,
however, the chance of being assigned to the treatment that has worked best so far will

Participants in the 5-aza and VPA group will receive 5-aza as an injection under the skin
once a day for 7 days in a row. On these same 7 days, participants in this group will also
take VPA by mouth twice a day or 3 times a day based on your weight. Seven (7) days is
considered 1 treatment cycle. Both drugs will be taken at the same time. Cycles will be
repeated every 4 to 6 weeks.

Participants in the ara-C group will receive ara-c twice a day as an injection under the
skin for 10 days (1 cycle). Cycles will be repeated every 4 to 6 weeks.

You will be monitored with routine blood tests (about 1-2 teaspoons each time) 2-3 times a
week during this study.

You may receive up to 12 cycles of therapy. You may be taken off study early if the disease
gets worse or intolerable side effects occur.

Once you go off study, you will have standard follow-up as is required by your primary

This is an investigational study. 5-aza is approved by the FDA for MDS. VPA is approved by
the FDA for epilepsy. Their use together in this study is experimental. Ara-C is approved
for acute myelogenous leukemia. About 70 patients will take part in this study. All will be
enrolled at M. D. Anderson.

Inclusion Criteria:

1. Patients must have untreated AML, or untreated MDS with > 10% blasts in marrow or

2. They must be at least age 60.

3. They must either have a serum creatinine > 1.9 mg/ml, a serum bilirubin > 1.9 mg/ml,
or a Zubrod performance status of 3 or 4.

4. Alternatively, they must not be candidates for protocols of higher priority.

5. They must provide written consent.

Exclusion Criteria:

1) Must not have the cytogenetic abnormalities inv (16), t (16;16) t (8;21), or t (15;17).
The relatively good prognoses of patients with these findings do not warrant use of 5
azacytidine, + valproic acid or low-dose ara-C (LDAC).

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants With Response

Outcome Description:

Patient response defined by: Death, Resistant to Therapy [no major hematologic improvement using International Myelodysplastic Syndromes (MDS) Working Group (Cheson B, Bennett J, Kantarjian H et al, Blood 2006) criteria after a maximum of 4 courses], or Relapse.

Outcome Time Frame:

Evaluated every 3 weeks, following 4 courses (16/24 weeks ) and till study end

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:




Start Date:

August 2005

Completion Date:

February 2008

Related Keywords:

  • Acute Myelogenous Leukemia
  • Myelodysplastic Syndrome
  • Leukemia
  • Acute Myelogenous Leukemia
  • AML
  • Myelodysplastic Syndrome
  • Leukemia
  • MDS
  • Azacytidine
  • 5-Azacytidine
  • 5-aza
  • Vidaza
  • 5-AZC
  • AZA-CR
  • Ladakamycin
  • Ara-C
  • Cytarabine
  • Cytosar
  • DepoCyt
  • Cytosine arabinosine hydrochloride
  • Valproic Acid
  • VPA
  • Depakene
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia



UT MD Anderson Cancer CenterHouston, Texas  77030