Erythropoietin (EPO)+/- Filgrastim (G-CSF) vs. Supportive Therapy Alone for Patients With Myelodysplastic Syndromes

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00003138
First received: November 1, 1999
Last updated: November 13, 2013
Last verified: November 2013
  Purpose

RATIONALE: Erythropoietin and colony-stimulating factors such as filgrastim stimulate the production of blood cells. It is not yet known whether erythropoietin with or without filgrastim is more effective than standard blood transfusions in reducing the need for transfusions in patients who have anemia associated with myelodysplastic syndrome.

PURPOSE: Randomized phase III trial to compare the effectiveness of erythropoietin with or without filgrastim with that of standard blood transfusions in reducing the need for transfusions in patients who have anemia associated with myelodysplastic syndrome.


Condition Intervention Phase
Anemia
Myelodysplastic Syndromes
Biological: Erythropoietin
Biological: Filgrastim
Procedure: Transfusion
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase III Evaluation of EPO With or Without G-CSF Versus Supportive Therapy Alone in the Treatment of Myelodysplastic Syndromes

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Proportion of Patients Free of Transfusion at 4 Months [ Time Frame: Assessed at 4 months ] [ Designated as safety issue: No ]
    Whether a patient required transfusion or not at 4 months was recorded.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: Assessed every 3 months for 2 years, every 6 months for 3 subsequent years, and annually thereafter ] [ Designated as safety issue: No ]
    Time from randomization to death from any cause. Patients alive at the time of analysis were censored at the date of last contact.

  • Quality of Life- Total Functional Assessment of Cancer Therapy - General (FACT-G) Score at 4 Months [ Time Frame: Assessed at 4 months ] [ Designated as safety issue: No ]
    The FACT-G scale has 4 dimensions, including physical well-being, social/family well-being, emotional well-being, and functional well-being. The score for each subscale was added together to obtain the total FACT-G score that was evaluated on this study. The total FACT-G score ranges from 0 to 108 with higher scores reflecting better quality of life. It was administered at the time of study entry, every 4 months for the first year, and at the time patient went off treatment. Due to limited data after 4 months on treatment, the analysis was restricted to the four-month time point.


Enrollment: 118
Study Start Date: December 1997
Estimated Study Completion Date: May 2014
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Supportive Care
Patients received red cell and platelet transfusions for symptoms or to maintain hematocrit at or above 25% by volume. Patients who required transfusion support for symptomatic anemia prior to entering the study and who developed an increase in their transfusion requirement of >= 50% shall cross over to the Erythropoietin treatment arm, after at least four months on the supportive therapy arm.
Procedure: Transfusion
Red cell and platelet transfusions
Experimental: Erythropoietin
Erythropoietin was administered at 150 units/kg subcutaneously every day. If patients stopped responding, they were subsequently treated with Erythropoietin (150 units/kg) and filgrastim and then Erythropoietin (300 units/kg) and filgrastim.
Biological: Erythropoietin
Administered at 150 units/kg subcutaneously every day. Rotating sites should be used. The dose should be rounded off to the nearest 1000 U. The dose should be adjusted based on hematocrit.
Other Names:
  • r-HuEPO
  • EPO
Biological: Filgrastim
G-CSF should start at a dose of 1 mcg/kg per day or 2.5 mcg/kg three times a week subcutaneously. Rotating sites should be used The dose should be rounded off to the nearest 10 mcg.
Other Names:
  • G-CSF
  • Neupogen
  • Recombinant-methionyl human granulocyte colony-stimulating factor
  • Granulocyte colony-stimulating factor
  • r-methHuG-CSF

Detailed Description:

OBJECTIVES:

  • Compare the benefit of erythropoietin vs standard transfusion support in reducing transfusion requirements in patients with myelodysplastic syndromes.
  • Compare the clinical response, disease progression, and survival in patients treated with these regimens.
  • Compare the toxicity of these regimens in these patients.
  • Evaluate whether adding filgrastim (G-CSF) or increasing the erythropoietin dose will reduce the transfusion requirement in patients who do not respond to erythropoietin alone.
  • To compare the benefit of erythropoietin versus supportive care alone on quality of life (QOL) in persons with myelodysplastic syndromes.

OUTLINE: This is a randomized, controlled, multicenter, cross-over study. Patients are stratified according to morphologic subtype (refractory anemia [RA] vs RA with ringed sideroblasts vs RA with excess blasts), transfusion requirement (yes vs no), prior erythropoietin treatment (yes vs no), and erythropoietin level (at least 200 mU/mL vs less than 200 mU/mL). Patients are randomized to one of two treatment arms.

  • Arm I (standard transfusion support): Patients receive red cell and platelet transfusions for symptoms or to maintain hematocrit level of 25% or above. Patients undergo bone marrow aspirate and biopsy at 4 months and then every year until development of acute leukemia or completion of study. Patients with progressive disease may cross over to arm II after at least 4 months on study and up to 1 year from the time of randomization. Patients who cross over receive erythropoietin alone.
  • Arm II (Erythropoietin): Patients receive erythropoietin subcutaneously (SC) or intravenously (IV) daily. Patients undergo bone marrow aspirate and biopsy as in arm I. Treatment continues daily for a maximum of 1 year.

Patients with stable or progressive disease at day 120 receive filgrastim (G-CSF) SC daily or 3 days a week and erythropoietin SC daily for up to 6 months. Patients with no response to G-CSF and lower-dose erythropoietin may proceed to a higher dose of erythropoietin.

Quality of life is assessed at baseline, every 4 months during study, and at study completion.

Patients are followed every 4 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

ACTUAL ACCRUAL: A total of 118 patients were accrued for this study.

  Eligibility

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

Inclusion Criteria:

  • At least 18 years of age
  • Diagnosis of a myelodysplastic syndrome
  • Refractory anemia (RA)
  • RA with ringed sideroblasts
  • RA with excess blasts (RAEB). RAEB patients must have a bone marrow blast count of less than 20% and less than 5% blast forms on peripheral blood
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 3
  • Platelet count greater than 30,000/mm^3 (without platelet transfusions)
  • Hematocrit less than 30% (pretransfusion)
  • Bilirubin less than 3 mg/dL
  • Blood urea nitrogen (BUN) less than 40 mg/dL or Creatinine less than 2.0 mg/dL
  • Prior epoetin alfa allowed provided dosage was less than 30,000 units per week for less than 1 month duration
  • At least 1 month since prior erythropoietin
  • At least 2 months since prior recombinant growth factor
  • At least 2 months since prior chemotherapy for other malignancy or autoimmune disease
  • At least 2 weeks since prior androgen or steroids for treatment of myelodysplastic syndromes

Exclusion Criteria:

  • RAEB in transformation
  • Chronic myelomonocytic leukemia
  • Splenomegaly greater than 6 cm below the left costal margin or greater than 3 times normal size
  • Uncontrolled hypertension
  • Sensitivity to E. coli-derived proteins
  • Sensitivity to epoetin alfa or any of its components (e.g., human albumin)
  • Documented iron deficiency. If marrow iron stain is not available, the transferrin saturation must be greater than 20% or ferritin greater than 100 ng/dL
  • Active infection or bleeding
  • Other uncontrolled malignancy
  • Pregnant or nursing. Fertile patients must use effective contraception.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003138

  Show 28 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Kenneth B. Miller, MD Beth Israel Deaconess Medical Center
  More Information

Additional Information:
Publications:
Miller KB, Kim HT, Greenberg P, et al.: Phase III prospective randomized trial of EPO with or without G-CSF versus supportive therapy alone in the treatment of myelodysplastic syndromes (MDS): results of the ECOG- CLSG trial (E1996). [Abstract] Blood 104 (11): A-70, 2004.
Dewald G, Hicks G, Higgins RR, et al.: Comparison of interphase fish and metaphase cytogenetics to study myelodysplasia: an Eastern Cooperative Oncology Group (ECOG) study. [Abstract] Blood 96 (11 Pt 1): A-635, 148a, 2000.

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00003138     History of Changes
Other Study ID Numbers: CDR0000065907, E1996, U10CA021115
Study First Received: November 1, 1999
Results First Received: September 11, 2013
Last Updated: November 13, 2013
Health Authority: United States: Federal Government

Keywords provided by Eastern Cooperative Oncology Group:
anemia
refractory anemia
myelodysplastic syndromes
erythropoietin
filgrastim

Additional relevant MeSH terms:
Anemia
Myelodysplastic Syndromes
Preleukemia
Hematologic Diseases
Bone Marrow Diseases
Precancerous Conditions
Neoplasms
Epoetin Alfa
Lenograstim
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 23, 2014