Azacitidine and Arsenic Trioxide in Treating Patients With Myelodysplastic Syndromes or Chronic Myelomonocytic Leukemia - Full Text View

Sponsored by:	Medical University of South Carolina
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00118196

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 II

MedlinePlus related topics: Arsenic Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Azacitidine Arsenic trioxide

U.S. FDA Resources

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

Further study details as provided by National Cancer Institute (NCI):

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
Estimated Primary Completion Date:	July 2007 (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

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:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000433313, MUSC-MDS2773, MUSC-15348
Study First Received:	July 8, 2005
Last Updated:	January 21, 2009
ClinicalTrials.gov Identifier:	NCT00118196 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
chronic myelomonocytic leukemia

Study placed in the following topic categories:

Antimetabolites
Chronic Myelomonocytic Leukemia
Precancerous Conditions
Hematologic Diseases
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Myeloproliferative Disorders
Arsenic trioxide

Leukemia, Myeloid
Leukemia
Preleukemia
Azacitidine
Neoplasm Metastasis
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Myelodysplastic Myeloproliferative Disease

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Disease
Molecular Mechanisms of Pharmacological Action
Precancerous Conditions
Antineoplastic Agents
Hematologic Diseases
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Arsenic trioxide
Enzyme Inhibitors

Leukemia, Myeloid
Pharmacologic Actions
Leukemia
Preleukemia
Neoplasms
Pathologic Processes
Therapeutic Uses
Syndrome
Azacitidine
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases

ClinicalTrials.gov processed this record on May 07, 2009