A Phase II Study of Arsenic Trioxide in Combination With 5-Azacitidine in Myelodysplastic Syndromes
18 Years
N/A
Both
Leukemia, Myelodysplastic Syndromes
Trial Information
A Phase II Study of Arsenic Trioxide in Combination With 5-Azacitidine in Myelodysplastic Syndromes
OBJECTIVES:
Primary
- Determine the response rate in patients with myelodysplastic syndromes or chronic
myelomonocytic leukemia treated with azacitidine and arsenic trioxide.
Secondary
- Determine time to treatment failure in patients treated with this regimen.
- Determine the tolerability and toxicity of this regimen in these patients.
- Determine progression-free survival of patients treated with this regimen.
OUTLINE: This a multicenter, non-randomized, open-label, study.
Patients receive azacitidine subcutaneously once daily on days 1-5 and arsenic trioxide IV
over 1-2 hours on days 1, 2, 8, 9, 15, 16, 22, and 23. Treatment repeats every 28 days for 4
courses in the absence of disease progression or unacceptable toxicity. Patients are
evaluated for response on day 113 (week 17). Patients with disease progression or no
response are removed from the study. Patients achieving a complete response (CR) receive 2
additional courses of therapy and then undergo observation. Patients achieving a partial
response receive 2 additional courses of therapy and then receive arsenic trioxide alone
twice weekly in the absence of CR, disease progression, or unacceptable toxicity.
After completion of study treatment, patients are followed every 2 months for at least 1
year.
PROJECTED ACCRUAL: A total of 19-41 patients will be accrued for this study within 18
months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of myelodysplastic syndrome or chronic myelomonocytic leukemia
- International Prognostic Scoring System (IPSS) score ≥ intermediate-1
- Low IPSS score allowed provided patient meets ≥ 1 of the following criteria:
- Platelet count ≤ 50,000/mm^3
- Required platelet or packed red cell transfusions within the past 4 weeks
- Neutropenic (i.e., absolute neutrophil count < 1,000/mm^3) AND has
infections requiring antibiotic treatment
- No prior leukemia or refractory anemia with excess blasts in transformation
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2
Life expectancy
- More than 12 weeks
Hematopoietic
- See Disease Characteristics
Hepatic
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN
Renal
- Creatinine ≤ 1.5 times ULN
Cardiovascular
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- Baseline QTc < 500 msec
- QTc interval < 460 msec with potassium > 4.0 mEq/L and magnesium > 1.8 mg/L
Immunologic
- No history of allergic reaction attributed to compounds of similar chemical or
biologic composition to study drugs
- No ongoing or active infection
- HIV negative
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 6 months after study
participation
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness
- No other malignancy within the past 12 months
PRIOR CONCURRENT THERAPY:
Biologic therapy
- More than 4 weeks since prior administration of any of the following:
- Interferon
- Filgrastim (G-CSF), sargramostim (GM-CSF), epoetin alfa, or other hematopoietic
cytokines
- Thalidomide or thalidomide analogs
- No concurrent epoetin alfa
Chemotherapy
- More than 4 weeks since prior chemotherapy
- No prior arsenic trioxide or azacitidine
- No other concurrent chemotherapy
Endocrine therapy
- More than 4 weeks since prior steroids
- No concurrent androgenic steroids
- Concurrent steroids for adrenal failure or as prophylaxis for nausea allowed
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- More than 4 weeks since prior retinoids
- No other concurrent investigational agents
- No other concurrent anticancer therapy
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Response rate (overall and confirmed) as measured by International Working Group (IWG) standardized criteria for MDS at day 113 and then every 4 weeks until completion of study treatment
Safety Issue:
No
Principal Investigator
Robert K. Stuart, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Medical University of South Carolina
Authority:
United States: Federal Government
Study ID:
CDR0000433313
NCT ID:
NCT00118196
Start Date:
April 2005
Completion Date:
July 2008
Related Keywords:
- Leukemia
- Myelodysplastic Syndromes
- de novo myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- chronic myelomonocytic leukemia
- Leukemia
- Leukemia, Myelomonocytic, Chronic
- Myelodysplastic Syndromes
- Preleukemia
- Leukemia, Myelomonocytic, Acute
Name | Location |
|---|---|
| Hollings Cancer Center at Medical University of South Carolina | Charleston, South Carolina 29425 |
