Decitabine, Arsenic Trioxide and Ascorbic Acid for Myelodysplastic Syndromes and Acute Myeloid Leukemia
A Phase I Study of Intravenous Decitabine in Combination With Arsenic Trioxide and Ascorbic Acid in Patients With Myelodysplastic Syndromes and Acute Myeloid Leukemia
1 other identifier
interventional
13
1 country
1
Brief Summary
This study is designed to test the combination of decitabine, arsenic trioxide and ascorbic acid in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started May 2008
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 1, 2008
CompletedStudy Start
First participant enrolled
May 1, 2008
CompletedFirst Posted
Study publicly available on registry
May 5, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2011
CompletedJune 4, 2013
May 1, 2013
1.7 years
May 1, 2008
May 31, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To define the maximum tolerated dose and dose-limiting toxicities during four cycles of combination decitabine, arsenic trioxide and ascorbic acid in patients with myelodysplastic syndromes (MDS) previously untreated with hypomethylating agents.
4 months after the final patient on the final cohort starts treatment
Secondary Outcomes (8)
To estimate the rate of complete remission (CR) and partial remission (PR) after four cycles of therapy in patients with MDS.
After 4 cycles of treatment
To determine the rate of hematologic improvement
Weekly through the end of treatment
To determine the rate of transfusion independence
Through completion of treatment
To determine the time to disease progression to AML
Every 4 weeks during treatment and then every 2 months for 2 years after the first dose of study drug
To determine the rate of cytogenetic response
After every 2 cycles
- +3 more secondary outcomes
Study Arms (3)
Dose Level 1 Arsenic Trioxide & Decitabine
EXPERIMENTALArsenic trioxide loading dose of 0.1 mg/kg/day IV x 5 days followed by weekly doses of 0.1 mg/kg IV for 15 additional weeks. Decitabine 20 mg/m2 IV every day on days 1-5 of a 4 weeks cycle for 4 cycles.
Dose Level 2 Arsenic Trioxide & Decitabine
EXPERIMENTALArsenic trioxide loading dose of 0.2 mg/kg/day IV x 5 days followed by weekly doses of 0.2 mg/kg IV for 15 additional weeks. Decitabine 20 mg/m2 IV every day on days 1-5 of a 4 weeks cycle for 4 cycles.
Dose Level 3 Arsenic Trioxide & Decitabine
EXPERIMENTALArsenic trioxide loading dose of 0.3 mg/kg/day IV x 5 days followed by weekly doses of 0.3 mg/kg IV for 15 additional weeks. Decitabine 20 mg/m2 IV every day on days 1-5 of a 4 weeks cycle for 4 cycles.
Interventions
Eligibility Criteria
You may qualify if:
- MDS (either de novo or secondary) fitting any of the FAB classifications or AML defined by FAB classification criteria. Patients with \< 5% bone marrow blasts must also meet one of the following criteria:
- Symptomatic anemia with either hemoglobin \<10.0 g/dL or requiring red blood cell (RBC) transfusion
- Thrombocytopenia with a history of two or more platelet counts \< 50,000 / µL or a significant hemorrhage requiring platelet transfusions, or
- Neutropenia with two or more absolute neutrophil counts \< 1,000 /µL.
- AML patients must also have a WBC \< 10,000µL and meet one of the following two criteria:
- Age greater than or equal to 60 years
- Relapsed AML and are not a candidate for cytotoxic chemotherapy.
- ECOG performance status of 0-2.
- Must give written informed consent indicating their awareness of the investigational nature of this study and its potential hazards.
- Adequate renal and hepatic function (creatinine \< 1.5x institutional upper limit of normal, total bilirubin ≤ 1.5x institutional upper limit of normal, AST and ALT ≤ 2x institutional upper limit of normal).
- Serum potassium \> 4.0 mEq/L, serum magnesium \> 1.8 mg/dL.
- Life expectancy of at least 16 weeks.
- Women of childbearing age must have a negative serum pregnancy test prior to initiating therapy.
- Sexually active women of childbearing potential must use effective birth control during the trial and for at least two months following the trial.
- Men must be willing to avoid fathering a new child while receiving therapy with decitabine.
- +2 more criteria
You may not qualify if:
- Known central nervous system (CNS) leukemia.
- Previously received greater than or equal to 5 cycles of azacitidine (Vidaza®, Pharmion Corp., Boulder, CO) or decitabine (Dacogen®, MGI Pharma Inc. Bloomington, MN).
- QTc \> 460 msec.
- Known or suspected hypersensitivity to decitabine, arsenic or ascorbic acid.
- Receiving any other investigational agents within 30 days of first dose of study drug.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure of NYHA class 3 or 4, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
- Known positive serology for HIV.
- Had radiotherapy within 14 days prior to study enrollment.
- Known presence of hepatic tumors.
- \< 18 years of age
- Exclude women who are pregnant or breast feeding.
- Known history of glucose-6-phosphate deficiency (G6PD).
- Currently taking a Class Ia or Class III antiarrhythmic or other medication causally associated with prolonging QTc.
- Use of aspirin with platelet counts \< 50,000/µl.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Washington University School of Medicinelead
- Cephaloncollaborator
Study Sites (1)
Washington University
St Louis, Missouri, 63110, United States
Related Publications (1)
Welch JS, Klco JM, Gao F, Procknow E, Uy GL, Stockerl-Goldstein KE, Abboud CN, Westervelt P, DiPersio JF, Hassan A, Cashen AF, Vij R. Combination decitabine, arsenic trioxide, and ascorbic acid for the treatment of myelodysplastic syndrome and acute myeloid leukemia: a phase I study. Am J Hematol. 2011 Sep;86(9):796-800. doi: 10.1002/ajh.22092. Epub 2011 Aug 3. No abstract available.
PMID: 21815182DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ravi Vij, M.D.
Washington Univerisity
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 1, 2008
First Posted
May 5, 2008
Study Start
May 1, 2008
Primary Completion
January 1, 2010
Study Completion
May 1, 2011
Last Updated
June 4, 2013
Record last verified: 2013-05