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

Sponsor

Genzyme, a Sanofi Company (Industry)

Overall Status

Completed

CT.gov ID

NCT00017550

Collaborator

(none)

Locations

Actual Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes	Biological: anti-thymocyte globulin	Phase 2

Detailed 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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Sep 1, 2000

Actual Primary Completion Date :

Nov 1, 2003

Actual Study Completion Date :

Nov 1, 2003

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington Cancer Institute	Washington	District of Columbia	United States	20010
2	University of Florida Health Science Center	Gainesville	Florida	United States	32610-0296
3	Sylvester Cancer Center, University of Miami	Miami	Florida	United States	33136
4	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612-9497
5	Veterans Affairs Medical Center - Tampa (Haley)	Tampa	Florida	United States	33612
6	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
7	Rush Cancer Institute	Chicago	Illinois	United States	60612
8	Indiana Blood and Marrow Transplant	Beech Grove	Indiana	United States	46107
9	Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242-1009
10	University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
11	Tulane University School of Medicine	New Orleans	Louisiana	United States	70112
12	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
13	University of Missouri Kansas City School of Medicine	Kansas City	Missouri	United States	64111
14	Saint Louis University Cancer Center	Saint Louis	Missouri	United States	63110-2539
15	Siteman Cancer Center	Saint Louis	Missouri	United States	63110
16	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-7680
17	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
18	New York Presbyterian Hospital - Cornell Campus	New York	New York	United States	10021
19	Mount Sinai Medical Center, NY	New York	New York	United States	10029
20	James P. Wilmot Cancer Center	Rochester	New York	United States	14642
21	New York Medical College	Valhalla	New York	United States	10595
22	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina	United States	27157-1082
23	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
24	Texas Oncology P.A.	Dallas	Texas	United States	75230-2503
25	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226-3596
26	Foothills Hospital	Calgary	Alberta	Canada	T2N 2T9
27	Department of Medicine	Vancouver	British Columbia	Canada	V5Z 4E3
28	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9