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A Phase II Study of Arsenic Trioxide in Combination With 5-Azacitidine in Myelodysplastic Syndromes


Phase 2
18 Years
N/A
Not Enrolling
Both
Leukemia, Myelodysplastic Syndromes

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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 CarolinaCharleston, South Carolina  29425