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

NCT ID: NCT00398047

Last Updated: 2018-09-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2009-09-30

Brief Summary

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.

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.

Conditions

Leukemia; Myelodysplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Azacitadine and Hematopoietic Growth Factors

Combination of Azacitadine andHematopoietic Growth Factors

Group Type: EXPERIMENTAL

Azacitadine and Hematopoietic Growth Factors

Intervention Type: DRUG

Combination of Azacitadine and Hematopoietic Growth Factors

Interventions

Azacitadine and Hematopoietic Growth Factors

Combination of Azacitadine and Hematopoietic Growth Factors

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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)

• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayard L. Powell, MD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Countries

United States

Other Identifiers

P30CA012197

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CCCWFU-29106

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000515108

Identifier Type: -

Identifier Source: org_study_id