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

This study has been completed.
Sponsor:
Information provided by:
Medical University of South Carolina
ClinicalTrials.gov Identifier:
NCT00118196
First received: July 8, 2005
Last updated: April 26, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
Drug: arsenic trioxide
Drug: azacitidine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Arsenic Trioxide in Combination With 5-Azacitidine in Myelodysplastic Syndromes

Resource links provided by NLM:


Further study details as provided by Medical University of South Carolina:

Primary Outcome Measures:
  • 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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to treatment failure as assessed by the Kaplan-Meier method at completion of study treatment [ Designated as safety issue: No ]
  • Progression-free survival as assessed by the Kaplan-Meier method at completion of study treatment [ Designated as safety issue: No ]
  • Toxicity as assessed by the Kaplan-Meier method and NCI-CTCAE version 3.0 during treatment until 30 days after completion of study treatment [ Designated as safety issue: Yes ]

Estimated Enrollment: 41
Study Start Date: April 2005
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00118196

Locations
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
Medical University of South Carolina
Investigators
Study Chair: Robert K. Stuart, MD Medical University of South Carolina
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00118196     History of Changes
Other Study ID Numbers: CDR0000433313, MUSC-MDS2773, MUSC-15348
Study First Received: July 8, 2005
Last Updated: April 26, 2012
Health Authority: United States: Federal Government

Keywords provided by Medical University of South Carolina:
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
chronic myelomonocytic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myelomonocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Azacitidine
Arsenic trioxide
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014