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

May 7, 2018 updated by: Medical University of South Carolina

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

1

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Hollings Cancer Center at Medical University of South Carolina

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Time to treatment failure as assessed by the Kaplan-Meier method at completion of study treatment
Progression-free survival as assessed by the Kaplan-Meier method at completion of study treatment
Toxicity as assessed by the Kaplan-Meier method and NCI-CTCAE version 3.0 during treatment until 30 days after completion of study treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of South Carolina

Investigators

  • Study Chair: Robert K. Stuart, MD, Medical University of South Carolina

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2005

Primary Completion (Actual)

August 11, 2006

Study Completion (Actual)

August 11, 2006

Study Registration Dates

First Submitted

July 8, 2005

First Submitted That Met QC Criteria

July 8, 2005

First Posted (Estimate)

July 11, 2005

Study Record Updates

Last Update Posted (Actual)

May 11, 2018

Last Update Submitted That Met QC Criteria

May 7, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000433313
  • MUSC-MDS2773
  • MUSC-15348

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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