Azacitidine With or Without MS-275 in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia - Full Text View

Sponsors and Collaborators:	Eastern Cooperative Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00313586

Purpose

RATIONALE: Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. MS-275 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving azacitidine together with MS-275 may kill more cancer cells.

PURPOSE: This randomized phase II trial is studying azacitidine and MS-275 to see how well they work compared to azacitidine alone in treating patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes	Drug: azacitidine Drug: entinostat	Phase II

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

Drug Information available for: Azacitidine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	A Randomized Phase II Trial of Azacitidine With or Without the Histone Deacetylase Inhibitor MS-275 for the Treatment of Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia (Dysplastic Type), and Acute Myeloid Leukemia With Multilineage Dysplasia

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

Primary Outcome Measures:

The complete response rate, partial response rate, and trilineage response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall response rate (complete response and partial response) [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]
Clinical mechanism of azacitidine with or without MS-275 as measured by methylation-specific real time PCR (MSP) assay [ Designated as safety issue: No ]

Estimated Enrollment:	152
Study Start Date:	August 2006
Estimated Primary Completion Date:	February 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental Patients receive azacitidine subcutaneously once daily on days 1-10.	Drug: azacitidine Given subcutaneously
Arm II: Experimental Patients receive azacitidine as in arm I and oral MS-275 on days 3 and 10.	Drug: azacitidine Given subcutaneously Drug: entinostat Given orally

Detailed Description:

OBJECTIVES:

Primary

Compare the overall response rate (complete, partial, and hematologic improvement-major by International Working Group [IWG] criteria) in patients with myelodysplastic syndromes, chronic myelomonocytic leukemia (dysplastic), or acute myeloid leukemia with multilineage dysplasia treated with azacitidine with vs without MS-275.
Compare the major response rate (complete and partial responses by IWG criteria) in patients treated with these regimens.

Secondary

Evaluate the toxicity of azacitidine and MS-275 in these patients.
Identify changes in gene promoter methylation and gene expression that may be associated with response to azacitidine and MS-275.
Identify other molecular mechanisms (such as DNA damage) that may be associated with response to azacitidine and MS-275.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease (myelodysplastic syndromes [MDS] high/intermediate-2 vs MDS low/intermediate-1 vs chronic myelomonocytic leukemia vs acute myeloid leukemia with multilineage dysplasia). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive azacitidine subcutaneously once daily on days 1-10.
Arm II: Patients receive azacitidine as in arm I and oral MS-275 on days 3 and 10.

Treatment in both arms repeats every 28 days for at least 6 and up to 24 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 152 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Bone marrow aspirate and/or biopsy-confirmed diagnosis of 1 of the following:
- Myelodysplastic syndromes (MDS)
  - Any International Prognostic Score (IPSS) eligible
    - Patients with low or intermediate-1 IPSS must have platelet count < 50,000/mm³ and/or absolute neutrophil count < 500/mm³
  - Blast count < 20%
- Chronic myelomonocytic leukemia (dysplastic subtype)
  - WBC < 12,000/mm³ (measured twice within the past 4 weeks, 2 weeks apart)
- Acute myeloid leukemia with multilineage dysplasia (AML-TLD)
  - Formerly diagnosed refractory anemia with excess blasts in transformation by FAB criteria allowed
  - AML-TLD by WHO criteria allowed in patients with no history of antecedent hematologic disorder
  - WBC ≤ 30,000/mm³ (measured twice within the past 4 weeks, 2 weeks apart)
    - WBC that has doubled over 4 weeks AND > 20,000/mm³ is not eligible
  - Evidence of ≥ 20% blasts on review of the bone marrow aspirate and/or biopsy
SWOG patients must be enrolled in research study trial SWOG-9007
No therapy-induced MDS or AML-TLD
No clinical evidence of CNS or pulmonary leukostasis or disseminated intravascular coagulation
No clinical evidence of CNS leukemia

PATIENT CHARACTERISTICS:

See Disease Characteristics
ECOG performance status 0-2
Life expectancy ≥ 6 months
Creatinine < 2.0 mg/dL
Bilirubin normal (unless due to intramedullary or extramedullary hemolysis, or Gilbert's syndrome)
AST and ALT ≤ 2.5 times upper limit of normal
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No active infections
No advanced malignant hepatic tumors
No other serious or uncontrolled medical conditions
No known hypersensitivity to azacitidine or mannitol

PRIOR CONCURRENT THERAPY:

Recovered from prior therapy
No prior azacitidine, decitabine or MS-275
No prior induction chemotherapy for AML or stem cell transplantation
No hematopoietic growth factors within 3 weeks prior to study entry
No other concurrent investigational or commercial agents or therapies for the malignancy
No concurrent valproic acid, epoetin alfa, or darbepoetin alfa
No filgrastim (G-CSF) or pegfilgrastim during days 1-10 of each treatment course

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00313586

Show 255 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Steven D. Gore, MD	Sidney Kimmel Comprehensive Cancer Center
Investigator:	Peter L. Greenberg, MD	Stanford University

More Information

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

Study ID Numbers:	CDR0000466186, ECOG-E1905
Study First Received:	April 11, 2006
Last Updated:	January 15, 2009
ClinicalTrials.gov Identifier:	NCT00313586
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

de novo myelodysplastic syndromes
untreated adult acute myeloid leukemia
chronic myelomonocytic leukemia
previously treated myelodysplastic syndromes

Study placed in the following topic categories:

Myelodysplastic syndromes
Precancerous Conditions
Chronic myelomonocytic leukemia
Hematologic Diseases
Leukemia, Myelomonocytic, Chronic
Myelodysplasia
Myelodysplastic Syndromes
Acute myelogenous leukemia
Myeloproliferative Disorders
Leukemia, Myeloid

Leukemia, Myeloid, Acute
Leukemia, Myelomonocytic, Acute
Myelodysplastic myeloproliferative disease
Leukemia
Preleukemia
Azacitidine
Acute myeloid leukemia, adult
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Acute myelocytic leukemia

Additional relevant MeSH terms:

Antimetabolites
Neoplasms
Antimetabolites, Antineoplastic
Pathologic Processes
Disease
Neoplasms by Histologic Type

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Syndrome
Enzyme Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009