Azacitidine, Darbepoetin Alfa, and Erythropoietin and Filgastrim (G-CSF) in Treating Patients With Myelodysplastic Syndromes

This study has been terminated.
(Slow accrual)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier:
NCT00398047
First received: November 9, 2006
Last updated: March 23, 2012
Last verified: March 2012
  Purpose

RATIONALE: Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of abnormal cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as darbepoetin alfa and G-CSF, may increase the number of red blood cells and white blood cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving azacitidine together with darbepoetin alfa and G-CSF may be an effective treatment for myelodysplastic syndromes.

PURPOSE: This clinical trial is studying how well giving azacitidine together with darbepoetin alfa and G-CSF works in treating patients with myelodysplastic syndromes.


Condition Intervention
Leukemia
Myelodysplastic Syndromes
Drug: Azacitadine and Hematopoietic Growth Factors

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Combination of Azacitadine and Hematopoietic Growth Factors for Myelodysplastic Syndrome

Resource links provided by NLM:


Further study details as provided by Comprehensive Cancer Center of Wake Forest University:

Primary Outcome Measures:
  • Number of Participants With Complete Response [ Time Frame: Approximately 112 days ] [ Designated as safety issue: No ]
    Complete response is normalization of abnormal blood counts, and disappearance of signs of morphological changes in the bone marrow. If the previously present cytogenetic abnormalities are absent then it is referred also as a cytogenetic complete remission.

  • Rate of Major Hematological Improvement [ Time Frame: Approximately 112 days ] [ Designated as safety issue: No ]
    For patients with pretreatment hemoglobin less than 11 g/dL, greater than 2 g/dL increase in hemoglobin; for red cell transfusion-dependent patients, transfusion independence.


Secondary Outcome Measures:
  • Minor Hematological Improvements [ Time Frame: Approximately 112 days ] [ Designated as safety issue: No ]
    For patients with pretreatment platelet count less than 100,000/mm3, a 50% or more increase in platelet count with a net increase greater than 10,000/mm3 but less than 30,000/mm3

  • Time to Progression to Acute Myeloid Leukemia (Blast ≥ 20%) or Death [ Time Frame: Approximately 12 months ] [ Designated as safety issue: No ]
    Death during treatment or disease progression characterized by worsening of cytopenias, increase in the percentage of the blasts, reduction of hemoglobin concentration by at least 2 g/dl or transfusion dependence in the absence of another explanation, such as acute infection, gastrointestinal bleeding, hemolysis.

  • Overall Survival [ Time Frame: Approximately 12 months ] [ Designated as safety issue: No ]
  • Change in Bone Marrow Apoptosis [ Time Frame: Baseline and approximately 12 months ] [ Designated as safety issue: No ]
  • Expression of p53 and p21 [ Time Frame: Approximately 12 months ] [ Designated as safety issue: No ]

Enrollment: 3
Study Start Date: September 2006
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Azacitadine and Hematopoietic Growth Factors
Combination of Azacitadine andHematopoietic Growth Factors
Drug: Azacitadine and Hematopoietic Growth Factors
Combination of Azacitadine and Hematopoietic Growth Factors

Detailed Description:

OBJECTIVES:

Primary

  • Determine the hematological response rate in patients with myelodysplastic syndromes treated with azacitidine, darbepoetin alfa, and filgrastim (G-CSF).

Secondary

  • Determine the time to leukemia progression, survival, and changes in apoptotic index of bone marrow in patients treated with this regimen.

OUTLINE: This is an open-label, nonrandomized study.

  • Initial therapy (courses 1 and 2): Patients receive azacitidine subcutaneously (SC) or intra-venous (IV) on days 1-5 (week 1) and darbepoetin alfa* SC on day 8 (week 2). Treatment repeats every 28 days for 2 courses.

Patients undergo bone marrow aspirate and biopsy to assess response. Patients with a major hematological improvement OR with grade 3-4 hematological toxicities during the first 2 courses of therapy AND/OR ≥ 50% reduction in bone marrow cellularity compared to baseline proceed to optimization therapy A. Patients not meeting any of the above criteria proceed to optimization therapy B. Patients with disease progression are removed from study.

  • Optimization therapy A (courses 3-8): Patients receive azacitidine SC or IV on days 1-5 (week 1), darbepoetin alfa** SC on day 8 (week 2), and filgrastim (G-CSF) SC 3 times weekly in weeks 2-4.
  • Optimization therapy B (courses 3-8): Patients receive a higher dose of azacitidine on days 1-5 (week 1), darbepoetin alfa** SC on day 8 (week 2), and G-CSF 3 times weekly in weeks 2-4.

In both optimization therapy A and B, treatment repeats every 28 days for 6 courses. Patients with any degree of hematological improvement after initial therapy and optimization therapy proceed to maintenance therapy.

  • Maintenance therapy (course 9 and all subsequent courses): Patients receive azacitidine on days 1-5 (week 1). Only patients with anemia (hemoglobin < 12 g/dL) and/or neutropenia (absolute neutrophil count < 1,500/mm ³) at the start of any given course during maintenance therapy receive darbepoetin alfa** SC beginning on day 8 (week 2) and continuing once every 21 days and G-CSF SC 3 times weekly beginning in week 2.

Courses repeat every 28-56 days (determined by the treating physician) in the absence of disease progression or unacceptable toxicity.

Bone marrow samples are obtained at baseline and after the completion of course 2 of study treatment for apoptosis analysis, flow cytometry, and gene expression profiles of p53 and p21 by immunohistochemistry. Peripheral blood samples are obtained periodically and analyzed for hemoglobin F quantitation.

NOTE: *Administered only if the patient is anemic (hemoglobin < 12 g/dL).

NOTE: **Darbepoetin alfa is held if hemoglobin > 12 g/dL on day 1 of a given cycle.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of myelodysplastic syndromes (MDS)

    • Bone marrow aspirate and biopsy with karyotyping performed within the past 8 weeks
  • Patients with chronic myelomonocytic leukemia (CMML), refractory anemia (RA), or refractory anemia with ringed sideroblasts (RARS) according to FAB classification OR RA, RARS, refractory anemia with multilineage dysplasia, or RARS with multilineage dysplasia according to WHO classification must meet ≥ 1 of the following criteria:

    • Symptomatic anemia requiring RBC transfusion for ≥ 3 months before study entry
    • Thrombocytopenia with ≥ 2 platelet counts < 50,000/mm³ OR a significant hemorrhage requiring platelet transfusion
    • Neutropenia with an absolute neutrophil count < 1,000/mm³ and an infection requiring IV antibiotics
  • No refractory anemia with excess blasts in transformation
  • No history of leukemia
  • No known primary or metastatic hepatic tumor

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy > 2 months
  • AST and ALT ≤ 2 times upper limit of normal
  • Creatinine < 2.0 mg/dL
  • Serum vitamin B12 normal
  • Serum and/or red cell folate levels normal
  • Ferritin ≥ 50 ng/mL
  • Copper > 40 µg/dL
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Negative pregnancy test

PRIOR CONCURRENT THERAPY:

  • No prior azacitidine or decitabine
  • No prior therapy for MDS

    • Supportive therapy within the past 28 days allowed
  • No other concurrent treatment for MDS (i.e., thalidomide, arsenic trioxide, cyclosporine, or melphalan)
  • No other concurrent hematopoietic growth factors, including epoetin alfa, filgrastim (G-CSF), sargramostim (GM-CSF), or interleukin-11 (oprelvekin)
  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: NCT00398047

Locations
United States, North Carolina
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
Sponsors and Collaborators
Comprehensive Cancer Center of Wake Forest University
Investigators
Principal Investigator: Bayard L. Powell, MD Comprehensive Cancer Center of Wake Forest University
  More Information

No publications provided

Responsible Party: Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier: NCT00398047     History of Changes
Other Study ID Numbers: CDR0000515108, P30CA012197, CCCWFU-29106
Study First Received: November 9, 2006
Results First Received: January 21, 2011
Last Updated: March 23, 2012
Health Authority: United States: Federal Government

Keywords provided by Comprehensive Cancer Center of Wake Forest University:
de novo myelodysplastic syndromes
refractory anemia with ringed sideroblasts
refractory anemia with excess blasts
refractory anemia
refractory cytopenia with multilineage dysplasia
chronic myelomonocytic leukemia
secondary myelodysplastic syndromes
childhood myelodysplastic syndromes

Additional relevant MeSH terms:
Leukemia
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 22, 2014