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

NCT ID: NCT00003138

Last Updated: 2023-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-03-04
• Study Completion Date: 2014-05-31

Brief Summary

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.

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.

Conditions

Anemia; Myelodysplastic Syndromes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Transfusion

Intervention Type: PROCEDURE

Red cell and platelet transfusions

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.

Group Type: EXPERIMENTAL

Erythropoietin

Intervention Type: BIOLOGICAL

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.

Filgrastim

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Transfusion

Red cell and platelet transfusions

Intervention Type: PROCEDURE

Other Intervention Names

r-HuEPO; EPO; G-CSF; Neupogen; Recombinant-methionyl human granulocyte colony-stimulating factor; Granulocyte colony-stimulating factor; r-methHuG-CSF

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kenneth B. Miller, MD

Role: STUDY_CHAIR

Beth Israel Deaconess Medical Center

Locations

CCOP - Colorado Cancer Research Program, Incorporated

Denver, Colorado, United States

Veterans Affairs Medical Center - Lakeside Chicago

Chicago, Illinois, United States

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

CCOP - Carle Cancer Center

Urbana, Illinois, United States

CCOP - Cedar Rapids Oncology Project

Cedar Rapids, Iowa, United States

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, United States

MBCCOP - LSU Health Sciences Center

New Orleans, Louisiana, United States

Tufts - New England Medical Center

Boston, Massachusetts, United States

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, United States

CCOP - Kalamazoo

Kalamazoo, Michigan, United States

West Michigan Cancer Center

Kalamazoo, Michigan, United States

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Veterans Affairs Medical Center - East Orange

East Orange, New Jersey, United States

CCOP - Northern New Jersey

Hackensack, New Jersey, United States

Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

NYU School of Medicine's Kaplan Comprehensive Cancer Center

New York, New York, United States

CCOP - Merit Care Hospital

Fargo, North Dakota, United States

MetroHealth's Cancer Care Center at MetroHealth Medical Center

Cleveland, Ohio, United States

CCOP - Columbus

Columbus, Ohio, United States

CCOP - Geisinger Clinic and Medical Center

Danville, Pennsylvania, United States

CCOP - Sioux Community Cancer Consortium

Sioux Falls, South Dakota, United States

CCOP - Scott and White Hospital

Temple, Texas, United States

CCOP - St. Vincent Hospital Cancer Center, Green Bay

Green Bay, Wisconsin, United States

CCOP - Marshfield Clinic Research Foundation

Marshfield, Wisconsin, United States

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, United States

Countries

United States

References

Cherry AM, Brockman SR, Paternoster SF, Hicks GA, Neuberg D, Higgins RR, Bennett JM, Greenberg PL, Miller K, Tallman MS, Rowe J, Dewald GW. Comparison of interphase FISH and metaphase cytogenetics to study myelodysplastic syndrome: an Eastern Cooperative Oncology Group (ECOG) study. Leuk Res. 2003 Dec;27(12):1085-90. doi: 10.1016/s0145-2126(03)00104-8.

Reference Type: BACKGROUND

PMID: 12921944 (View on PubMed)

Greenberg PL, Sun Z, Miller KB, Bennett JM, Tallman MS, Dewald G, Paietta E, van der Jagt R, Houston J, Thomas ML, Cella D, Rowe JM. Treatment of myelodysplastic syndrome patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase 3 trial by the Eastern Cooperative Oncology Group (E1996). Blood. 2009 Sep 17;114(12):2393-400. doi: 10.1182/blood-2009-03-211797. Epub 2009 Jun 29.

Reference Type: RESULT

PMID: 19564636 (View on PubMed)

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.

Reference Type: RESULT

Other Identifiers

E1996

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA021115

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000065907

Identifier Type: -

Identifier Source: org_study_id