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

Anemia Clinical Trial

Official title:

Phase III Evaluation of EPO With or Without G-CSF Versus Supportive Therapy Alone in the Treatment of Myelodysplastic Syndromes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003138
• Other study ID #: CDR0000065907
• Secondary ID: E1996U10CA021115
• Status: Completed
• Phase: Phase 3
• Start date: March 4, 1998
• Est. completion date: May 2014

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• Est. completion date: May 2014
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

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.
• 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.

Procedure:
• Transfusion
Red cell and platelet transfusions

Locations

Country	Name	City	State
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Tufts - New England Medical Center	Boston	Massachusetts
United States	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Veterans Affairs Medical Center - Lakeside Chicago	Chicago	Illinois
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 - Colorado Cancer Research Program, Incorporated	Denver	Colorado
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey
United States	CCOP - Merit Care Hospital	Fargo	North Dakota
United States	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin
United States	CCOP - Northern New Jersey	Hackensack	New Jersey
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	CCOP - Carle Cancer Center	Urbana	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

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: — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients Free of Transfusion at 4 Months	Whether a patient required transfusion or not at 4 months was recorded.	Assessed at 4 months
Secondary	Overall Survival	Time from randomization to death from any cause. Patients alive at the time of analysis were censored at the date of last contact.	Assessed every 3 months for 2 years, every 6 months for 3 subsequent years, and annually thereafter
Secondary	Quality of Life- Total Functional Assessment of Cancer Therapy - General (FACT-G) Score at 4 Months	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.	Assessed at 4 months