Myelodysplastic Syndromes and Leukemia, Myeloid, Acute Clinical Trial
Official title:
A Phase I Study of Intravenous Decitabine in Combination With Arsenic Trioxide and Ascorbic Acid in Patients With Myelodysplastic Syndromes and Acute Myeloid Leukemia
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
| Status | Completed |
| Enrollment | 13 |
| Est. completion date | May 2011 |
| Est. primary completion date | January 2010 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: 1. 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: 1. Symptomatic anemia with either hemoglobin <10.0 g/dL or requiring red blood cell (RBC) transfusion 2. Thrombocytopenia with a history of two or more platelet counts < 50,000 / µL or a significant hemorrhage requiring platelet transfusions, or 3. 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: 1. Age greater than or equal to 60 years 2. Relapsed AML and are not a candidate for cytotoxic chemotherapy. 2. ECOG performance status of 0-2. 3. Must give written informed consent indicating their awareness of the investigational nature of this study and its potential hazards. 4. 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). 5. Serum potassium > 4.0 mEq/L, serum magnesium > 1.8 mg/dL. 6. Life expectancy of at least 16 weeks. 7. Women of childbearing age must have a negative serum pregnancy test prior to initiating therapy. 8. Sexually active women of childbearing potential must use effective birth control during the trial and for at least two months following the trial. 9. Men must be willing to avoid fathering a new child while receiving therapy with decitabine. 10. Greater than or equal to 18 years, no upper age limit 11. Individuals who are candidates for hematopoietic stem cell transplantation and who meet all other study criteria may participate in the study and receive intravenous decitabine in combination with arsenic trioxide and Ascorbic acid as a treatment prior to transplantation. Exclusion Criteria: 1. Known central nervous system (CNS) leukemia. 2. Previously received greater than or equal to 5 cycles of azacitidine (Vidaza®, Pharmion Corp., Boulder, CO) or decitabine (Dacogen®, MGI Pharma Inc. Bloomington, MN). 3. QTc > 460 msec. 4. Known or suspected hypersensitivity to decitabine, arsenic or ascorbic acid. 5. Receiving any other investigational agents within 30 days of first dose of study drug. 6. 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. 7. Known positive serology for HIV. 8. Had radiotherapy within 14 days prior to study enrollment. 9. Known presence of hepatic tumors. 10. < 18 years of age 11. Exclude women who are pregnant or breast feeding. 12. Known history of glucose-6-phosphate deficiency (G6PD). 13. Currently taking a Class Ia or Class III antiarrhythmic or other medication causally associated with prolonging QTc. 14. Use of aspirin with platelet counts < 50,000/µl. |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United States | Washington University | St. Louis | Missouri |
| Lead Sponsor | Collaborator |
|---|---|
| Washington University School of Medicine | Cephalon |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | Yes | |
| Secondary | 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 | No | |
| Secondary | To determine the rate of hematologic improvement | Weekly through the end of treatment | No | |
| Secondary | To determine the rate of transfusion independence | Through completion of treatment | No | |
| Secondary | 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 | No | |
| Secondary | To determine the rate of cytogenetic response | After every 2 cycles | No | |
| Secondary | To determine the rate of overall survival | Every 4 weeks during treatment and then every 2 months for 2 years after the first dose of study drug | No | |
| Secondary | To determine changes in bone marrow vascular density | At baseline, end of cycle 2, end of cycle 4, and end of study | No | |
| Secondary | To determine changes in angiogenic mRNA expression. | Baseline, end of cycle 2, end of cycle 4, and end of study | No |