Antithymocyte Globulin and Cyclosporine Compared With Standard Therapy in Treating Patients With Myelodysplastic Syndrome - Full Text View

Sponsor:	Swiss Group for Clinical Cancer Research
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00004208

Purpose

RATIONALE: Antithymocyte globulin and cyclosporine may improve blood counts in patients with myelodysplastic syndrome. It is not yet known whether antithymocyte globulin and cyclosporine are more effective than standard therapy for myelodysplastic syndrome.

PURPOSE: This randomized phase III trial is studying antithymocyte globulin and cyclosporine to see how well they work compared to standard therapy in treating patients with myelodysplastic syndrome.

Condition	Intervention	Phase
Myelodysplastic Syndromes	Biological: anti-thymocyte globulin Drug: cyclosporine	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Primary Purpose: Treatment
Official Title:	Antithymocyte Globulin (ATG) and Cyclosporine (CSA) to Treat Patients With Myelodysplastic Syndrome (MDS) - A Randomized Trial Comparing ATG + CSA With Best Supportive Care

Resource links provided by NLM:

MedlinePlus related topics: Anemia Myelodysplastic Syndromes

Drug Information available for: Cyclosporine Cyclosporin

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Complete and partial response rate at month 6 [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response rate at month 3 [ Designated as safety issue: No ]
Quality and duration of response at 2 and 5 years after first response [ Designated as safety issue: No ]
Proportion of relapse to progression in responders at 2 and 5 years after first response [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Leukemia-free survival [ Designated as safety issue: No ]
Transformation-free survival [ Designated as safety issue: No ]

Estimated Enrollment:	84
Study Start Date:	August 2000

Detailed Description:

OBJECTIVES:

Compare the efficacy and toxicity of antithymocyte globulin and cyclosporine versus best supportive care in patients with transfusion dependent low or intermediate risk myelodysplastic syndrome.
Determine whether immunosuppression improves hematopoiesis and reduces transfusion requirements of these patients.
Determine whether immunosuppression accelerates leukemic transformation and influences survival of these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by center and risk group.

Patients are randomized to 1 of 2 treatment arms:

Arm I: Patients receive antithymocyte globulin IV over 3 hours on days 1-5 and oral cyclosporine twice daily on days 1-180.
Arm II: Patients receive standard supportive care without antithymocyte globulin and cyclosporine.

Patients are followed at 1, 3, and 6 months, then every 6 months for 1.5 years, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 84 patients (42 per arm) will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of low or intermediate risk myelodysplastic syndrome (MDS) of less than 2 years duration with any of the following:
- Hypoplasia
- Refractory anemia
- Refractory anemia with sideroblasts
- Refractory anemia with excess of blasts (RAEB) with no greater than 10% blast cells in bone marrow
- RAEB with 10-20% blast count, and patient refuses intensive chemotherapy on high risk MDS protocol (EORTC 06961) and is not eligible for bone marrow transplantation
Transfusion dependence, defined by any of the following:
- Packed red blood cell transfusions greater than 2 units per month for a period of at least 2 months
- Untransfused hemoglobin level no greater than 8 g/dL
- Platelet transfusions greater than 1 unit per 2 weeks for a period of greater than 1 month
- Untransfused platelet count no greater than 20,000/mm^3
No chronic myelomonocytic leukemia
No refractory anemia with excess blasts in transformation
Not scheduled for a bone marrow transplantation

PATIENT CHARACTERISTICS:

Age:

Over 18

Performance status:

ECOG/SAKK 0-2

Life expectancy:

Not specified

Hematopoietic:

See Disease Characteristics

Hepatic:

Bilirubin no greater than 2.5 times upper limit of normal (ULN)
No active chronic hepatitis B or C

Renal:

Creatinine no greater than 2.5 times ULN

Cardiovascular:

No history of heart failure
No clinically relevant cardiac arrhythmia

Other:

No other prior malignancy except nonmelanomatous skin cancer or adequately treated carcinoma in situ of the cervix
No history of allergy to horse proteins, anaphylactic reactions to animal proteins, or serum sickness
Not pregnant
Fertile patients must use effective contraception
HIV negative
No active uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

See Disease Characteristics

Chemotherapy:

No prior chemotherapy

Endocrine therapy:

Not specified

Radiotherapy:

No prior radiotherapy

Surgery:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004208

Locations

Switzerland
Universitaetsspital-Basel
Basel, Switzerland, CH-4031

Sponsors and Collaborators

Swiss Group for Clinical Cancer Research

Investigators

Study Chair:

A. Tichelli, MD

Universitaetsspital-Basel

More Information

Publications:

Passweg JR, Giagounidis AA, Simcock M, Aul C, Dobbelstein C, Stadler M, Ossenkoppele G, Hofmann WK, Schilling K, Tichelli A, Ganser A. Immunosuppressive Therapy for Patients With Myelodysplastic Syndrome: A Prospective Randomized Multicenter Phase III Trial Comparing Antithymocyte Globulin Plus Cyclosporine With Best Supportive Care--SAKK 33/99. J Clin Oncol. 2010 Dec 13; [Epub ahead of print]

Passweg JR, Giagounidis A, Simcock M, et al.: Immunosuppression for patients with low and intermediate risk myelodysplastic syndrome: a prospective randomized multicenter trial comparing antithymocyte globulin + cyclosporine with best supportive care: SAKK 33/99. [Abstract] Blood 110 (11): A-1461, 2007.

ClinicalTrials.gov Identifier:	NCT00004208 History of Changes
Other Study ID Numbers:	CDR0000067455, SWS-SAKK-33/99
Study First Received:	January 21, 2000
Last Updated:	January 15, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

refractory anemia
refractory anemia with ringed sideroblasts
refractory anemia with excess blasts

de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes

Additional relevant MeSH terms:

Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Antilymphocyte Serum
Cyclosporins
Cyclosporine
Immunosuppressive Agents

Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on February 12, 2012