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A Pilot Phase II Study of Decitabine, Arsenic Trioxide and Ascorbic Acid for Patients With Myelodysplastic Syndrome

Phase 2
18 Years
Not Enrolling
Myelodysplastic Syndrome

Thank you

Trial Information

A Pilot Phase II Study of Decitabine, Arsenic Trioxide and Ascorbic Acid for Patients With Myelodysplastic Syndrome

Conventional therapy for MDS has been poor at best. Supportive care with transfusion
therapy and antibiotics have remained an option for all patients with myelodysplastic
syndrome (MDS).

The only known curative therapy is an allogeneic bone marrow transplant. However due to its
high morbidity in this elderly population and the lack of available donors, it is estimated
that less than 5% of patients with MDS are candidates for this type of aggressive therapy.
Investigational therapies are thus warranted in MDS.

Decitabine shows significant clinical activity in patients with MDS, with moderate toxicity.
The major toxicity is myelosuppression with subsequent infection occurring in 20-25% of

Arsenic trioxide is an FDA approved drug for the treatment of patients with acute
promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and
anthracycline chemotherapy. Two pivotal studies of arsenic trioxide in the setting of
relapsed APL showed a complete remission rate of 87% with a 36 month survival estimate of
50%. As of May 2004, over 800 patients had received arsenic trioxide in clinical studies or
through a compassionate use program, and an additional 3600 patients had received the drug
in clinical practice.

Arsenic trioxide shows clinical activity in MDS. Side effects have been noted and are

Adult patients with an established diagnosis of MDS will receive decitabine 20 mg/m2 IV over
one hour for days1-5 of each cycle, and arsenic trioxide 0.25 mg/kg IV for days 1-5 of
cycle 1 followed by 0.25 mg/kg twice weekly (Mon-Thursday or Tues-Fri) for all remaining
cycles. The dose of ascorbic acid will be 1000 mg in 100 mL a solution of 5% dextrose in
water (D5W) (protected from light and air) administered as an IV infusion over 15 to 30
minutes and administered within 30 minutes after arsenic trioxide administration.

Each cycle will consist of 4 weeks of treatment, and patients will be assessed each cycle
for toxicity, and after 4 cycles for response as defined by the International Working Group
(IWG - see section 8.0). Patients will have transfusion and supportive care therapy
administered per the treating physician's discretion.

Patients with a response (complete response - CR, partial remission - PR, or hematologic
improvement) after 4 cycles of therapy may choose to continue on two more cycles of
decitabine with arsenic and ascorbic acid given only during the first week of those two
additional cycles.

Inclusion Criteria:

- Established diagnosis of MDS (de novo or secondary) fitting either the French
American British Cooperative Group (FAB) or World Health Organization (WHO)
classification systems as determined by a complete blood count (CBC) and bone marrow
biopsy. Patients with >20% bone marrow blasts but <30% bone marrow blasts who would
be classified as refractory anemia with excess blasts (RAEB-t) in the FAB and acute
myeloid leukemia (AML) in the WHO systems are still eligible for this study.
Patients with low risk MDS (IPSS scores low or intermediate -1 (INT-1) must be
transfusion dependent to be eligible. Transfusion dependent will be defined as having
2 or more transfusion events within a 90 day period.

- Eastern Oncology Cooperative Group (ECOG) or WHO performance status of 0-2 (Appendix)

- Able to provide written informed consent.

Exclusion Criteria:

- Pregnant females

- AML defined as > 30% bone marrow blasts.

- Any malignant disease within the past 2 years, except cervical carcinoma, basal cell
carcinoma of the skin, and squamous cell carcinoma of the skin..

- Off all prior treatment for MDS for at least 4 weeks from entry.

- Off any investigational agents for at least 4 weeks from entry.

- Uncontrolled cardiac disease or congestive heart failure as defined by New York Heart
Association criteria of Class III or greater.

- Uncontrolled pulmonary disease.

- Uncontrolled or active viral or bacterial infection. All infections must have been
fully treated with antibiotics.

- HIV +

- Lab values as specified in the protocol

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Patients With an Overall Response of Complete Response (CR) or Partial Response (PR)

Outcome Description:

Complete response and Partial response are defined using 2000 international working group (IWG) criteria. The Primary criteria for a CR is a repeat bone marrow showing < 5% myeloblasts with normal maturation of all cell lines, with no evidence for dysplasia . A PR meets all the CR criteria except Blasts decreased by >50% over pretreatment, or a less advanced myelodysplastic syndrome (MDS) French American British (FAB) classification than pretreatment.

Outcome Time Frame:

after 4 cycles of therapy

Safety Issue:


Principal Investigator

Carlos de Castro, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University


United States: Institutional Review Board

Study ID:




Start Date:

November 2007

Completion Date:

April 2010

Related Keywords:

  • Myelodysplastic Syndrome
  • Myelodysplastic syndrome
  • MDS
  • Myelodysplastic Syndromes
  • Preleukemia



Duke University Medical CenterDurham, North Carolina  27710