Azacitidine and Arsenic Trioxide in Treating Patients With Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia

Medical University of South Carolina (MUSC)

Status and phase

Terminated

Phase 2

Conditions

Leukemia

Myelodysplastic Syndromes

Treatments

Drug: arsenic trioxide

Drug: azacitidine

Study type

Interventional

Funder types

Other

Identifiers

NCT00118196

MUSC-MDS2773

CDR0000433313

MUSC-15348

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as azacitidine and arsenic trioxide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving azacitidine together with arsenic trioxide works in treating patients with myelodysplastic syndromes or chronic myelomonocytic leukemia.

Full description

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.

Enrollment

1 patient

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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