Antithymocyte Globulin Compared With Supportive Care in Treating Patients With Myelodysplastic Syndrome

Myelodysplastic Syndromes Clinical Trial

Official title:

An Open Label, Prospective, Stratified, Randomized, Controlled, Multi-Center, Phase IIB Study of the Impact of Thymoglobulin Therapy on Transfusion Needs of Patients With Early Myelodysplastic Syndrome (MDS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00017550
• Other study ID #: CDR0000068709
• Secondary ID: SMC-101-1020RUSH
• Status: Completed
• Phase: Phase 2
• Start date: September 2000
• Est. completion date: November 2003

Study information

• Verified date: March 2003
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Immunosuppressive therapy may improve bone marrow abnormalities and may be effective treatment for myelodysplastic syndrome. It is not yet known whether immunosuppressive therapy is more effective than supportive care in treating myelodysplastic syndrome.

PURPOSE: Randomized phase II trial to compare the effectiveness of antithymocyte globulin with that of supportive care in treating patients who have myelodysplastic syndrome.

Description:

OBJECTIVES:

• Compare the clinical response rate of patients with early myelodysplastic syndrome treated with rabbit anti-thymocyte globulin vs standard supportive care.

• Evaluate the safety of anti-thymocyte globulin in these patients.

• Compare the time to and duration of clinical response, rates of partial response and therapy failure, and rate of disease progression in patients treated with these regimens.

• Compare the ECOG performance score, number of transfusions and/or growth factor use, and maximum time between transfusions in patients treated with these regimens.

• Compare the infection risk, use of medical resources, and quality of clinical response in patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to myelodysplastic syndrome (MDS) subtype (refractory anemia (RA) vs RA with excess blasts or hypocellular MDS). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive rabbit anti-thymocyte globulin (ATG) IV over at least 8-12 hours on days 1-4.

• Arm II: Patients receive standard supportive therapy for 6 months. At the end of 6 months, patients may receive ATG as in arm I.

Patients are followed for 6 months.

PROJECTED ACCRUAL: A total of 72 patients (48 in arm I and 24 in arm II) will be accrued within a minimum of 6 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: November 2003
• Est. primary completion date: November 2003
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed early myelodysplastic syndrome (MDS) with less than 10% bone marrow blasts

• Refractory anemia (RA)

• RA with excess blasts (RAEB)

• Hypocellular myelodysplasia

• Low or intermediate-1 prognostic risk

• Transfusion-dependent

• Need for 2 or more units of red blood cells or platelets per month for 2 or more months prior to study OR

• History of prior transfusions and 2 consecutive (at least 21 days apart) hemoglobin levels less than 8.0 g/dL or platelet counts less than 20,000/mm^3 during the past 2 months

• Hemoglobin no greater than 12.0 g/dL after prior transfusion

• No myelosclerosis occupying more than 30% of bone marrow space

• No RA with ringed sideroblasts, RAEB in transformation, or chronic myelomonocytic leukemia

• No therapy-related MDS

• No history of immune-related hematologic disorder (e.g., idiopathic thrombocytopenic purpura)

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• See Disease Characteristics

• No other causes of cytopenia unrelated to MDS (e.g., gastrointestinal blood loss)

• Iron present on marrow examination OR

• Transferrin saturation at least 20% and ferritin at least 50 ng/mL

Hepatic:

• Bilirubin no greater than 2 mg/dL OR

• SGOT/SGPT no greater than 2 times normal

• No active or chronic hepatitis B or C

Renal:

• Creatinine no greater than 2 mg/dL

Cardiovascular:

• No symptomatic cardiac disease

• No congestive heart failure (even if medically controlled)

• No myocardial infarction within the past 6 months

Pulmonary:

• No severe pulmonary disease

• If history of pulmonary insufficiency, must have pO_2 at least 90 mm/Hg on room air or pCO_2 no greater than 40 mm/Hg

Other:

• No history of unresolved B12 or folate deficiency since diagnosis of MDS

• No untreated acute or chronic infection (afebrile for 7 days without antibiotics prior to study)

• No active or chronic HIV

• No concurrent cytomegalovirus infection

• No other malignancy within the past 2 years except adequately treated localized squamous cell or basal cell skin cancer or carcinoma in situ of the cervix

• No concurrent drug or alcohol abuse

• No significant medical or psychosocial problems

• No known allergy to rabbit protein

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 8 weeks since prior biologic agents, colony-stimulating factors, or epoetin alfa for MDS

• At least 8 weeks since other prior investigational biologic agents

• No prior or concurrent bone marrow transplantation

• No concurrent epoetin alfa

• No concurrent growth factors except filgrastim (G-CSF) or sargramostim (GM-CSF) for neutropenic fevers

• No other concurrent biologic agents

Chemotherapy:

• At least 8 weeks since prior cytotoxic drugs for MDS

• Concurrent chemotherapy for clinical indications of disease progression or leukemic transformation allowed

Endocrine therapy:

• At least 8 weeks since prior androgenic hormonal therapy for MDS

• At least 8 weeks since prior danazol for MDS

Radiotherapy:

• No prior radiotherapy

Surgery:

• No prior organ transplantation

Other:

• At least 8 weeks since prior investigational drugs

• At least 8 weeks since prior immunosuppressive drugs or other drugs for MDS

• No concurrent immunosuppressive therapy

• No other concurrent experimental drugs

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Biological:
• anti-thymocyte globulin

Locations

Country	Name	City	State
Canada	Foothills Hospital	Calgary	Alberta
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Department of Medicine	Vancouver	British Columbia
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Indiana Blood and Marrow Transplant	Beech Grove	Indiana
United States	Rush Cancer Institute	Chicago	Illinois
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Texas Oncology P.A.	Dallas	Texas
United States	University of Florida Health Science Center	Gainesville	Florida
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of Missouri Kansas City School of Medicine	Kansas City	Missouri
United States	Sylvester Cancer Center, University of Miami	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Mount Sinai Medical Center, NY	New York	New York
United States	New York Presbyterian Hospital - Cornell Campus	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	James P. Wilmot Cancer Center	Rochester	New York
United States	Saint Louis University Cancer Center	Saint Louis	Missouri
United States	Siteman Cancer Center	Saint Louis	Missouri
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Veterans Affairs Medical Center - Tampa (Haley)	Tampa	Florida
United States	New York Medical College	Valhalla	New York
United States	Washington Cancer Institute	Washington	District of Columbia
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Countries where clinical trial is conducted

United States,  Canada,