Cephalon Decitabine, Arsenic Trioxide and Ascorbic Acid for Myelodysplastic Syndrome

NCT00621023 | Completed Phase 2 Results DMC

• 2 other identifiers: Pro000117927667A
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This will be an open-label, non-randomized trial pilot phase II trial open to patients with myelodysplastic syndrome. The purpose of the study is to find out if the combination of decitabine, arsenic trioxide and ascorbic acid is safe.

Conditions

Myelodysplastic Syndrome

Keywords

Myelodysplastic syndrome; MDS

Outcome Measures

Primary Outcomes (1)

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

  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.

  after 4 cycles of therapy

Secondary Outcomes (2)

• Duration of a Complete or Partial Response Based on Number of People Who Responded.

  Up to 5 years or until death

• Number of Patients With an Unacceptable Toxicity

  During the treatment period and for 30 days after last dose of study drug

Study Arms (1)

1

EXPERIMENTAL

Drug: Decitabine, Arsenic Trioxide and Ascorbic Acid for MDS

Drug: Decitabine, Arsenic Trioxide and Ascorbic Acid

Interventions

Decitabine, Arsenic Trioxide and Ascorbic Acid DRUG

Subjects 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. Patients will have transfusion and supportive care therapy administered per the treating physician's discretion. Patients with a response 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.

Also known as: Decitabine, ATO

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• Cephalon: collaborator
• Eisai Inc.: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Decitabine; Arsenic Trioxide; Ascorbic Acid

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Carbohydrates

Limitations and Caveats

Enrollment stopped early, which lead to a small number of subjects analyzed. The subjects who were enrolled did complete the entire protocol and their data was analyzed.

Results Point of Contact

• Title: Dr. Carlos de Castro
• Organization: Duke University Medical Center

decas003@mc.duke.edu

919-684-8964

Study Officials

• Carlos de Castro, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2007
• First Posted: February 22, 2008
• Study Start: November 1, 2007
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: February 4, 2013
• Results First Posted: January 28, 2013

Record last verified: 2013-01

Locations

US (1)