Antithymocyte Globulin and Cyclosporine in Treating Low Risk Patients With Myelodysplastic Syndrome - Full Text View

Purpose

The different mechanisms of action between Antithymocyte globulin and cyclosporine can improve the effectivity when both are used in combination in patients with myelodysplastic syndrome.

Condition	Intervention	Phase
Myelodysplastic Syndrome	Drug: Antithymocyte globulin Drug: Cyclosporine	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	SMD/ATG-CSA: Antithymocyte Globulin and Cyclosporine in Treating Low Risk Patients With Myelodysplastic Syndrome

Resource links provided by NLM:

MedlinePlus related topics: Myelodysplastic Syndromes

Drug Information available for: Cyclosporine Antilymphocyte Serum

U.S. FDA Resources

Further study details as provided by PETHEMA Foundation:

Primary Outcome Measures:

Compare the efficacy and toxicity of antithymocyte globulin and cyclosporine in patients with low risk myelodysplastic syndrome [ Time Frame: 3 years ]

Estimated Enrollment:	25
Study Start Date:	May 2002
Study Completion Date:	December 2007
Primary Completion Date:	June 2007 (Final data collection date for primary outcome measure)

Detailed Description:

Patients are treated with:

Antithymocyte globulin (Timoglobulin SangStat)

2,5 mg/kg/day IV over 8 hours on days 1-4
Total dose: 10 mg/kg
Calculated dose adjusted to ideal weight
Especial considerations:

Paracetamol 1 gr (oral or IV) Dexclorfeniramine 5 mg IV Methylprednisolone 1 mg/kg IV 30 minutes before Timoglobulin and repeat if necessary at 4 hours - Platelet transfusion if platelet count is < 50 x 109/L

Cyclosporine (Sandimmun Neoral)

-2,5 mg/kg/12 h over 3 months

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosis of low or intermediate risk myelodysplastic syndrome (MDS) (or high risk patient not eligible to intensive chemotherapy or for bone marrow transplantation), excluding chronic myelomonocytic leukemia
At less one of two following conditions:
Transfusion dependence: 1)Packed red blood cell transfusions greater than 2 times; 2)Untransfused hemoglobin level no greater than 10 g/dL; 3)Platelet transfusions greater than 1 time
Infection grade III or IV secondary to neutropenia
ECOG < or = 2

Exclusion Criteria:

Chronic myelomonocytic leukemia
Creatinine greater than 2 mg/dl
Bilirubin greater than 2.5 mg/dl
History of heart failure
History of allergy to rabbit proteins

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00488436

Locations

Spain
Hospital de Cabueñes
Asturias, Spain
Hospital germans Trias i Pujol
Badalona, Spain
Hospital de Basurto
Bilbao, Spain
Hospital Ntra Sra del Rossell
Cartagena, Spain
Hospital Materno Infantil de Las Palmas
Las Palmas de Gran Canaria, Spain
Hospital Virgen de la Victoria
Malaga, Spain
Hospital Morales Messeguer
Murcia, Spain
Hospital de Navarra
Pamplona, Spain
Hospital Dr Pesset
Valencia, Spain
Hospital Arnau de Vilanova
Valencia, Spain
Hospital Clinico Universitario
Zaragoza, Spain

Sponsors and Collaborators

PETHEMA Foundation

Investigators

Study Director:	Sanz Guillermo, Dr	HOSPITAL LA FE VALENCIA
Study Director:	Julia Antonio, Dr	Hospital Vall d'Hebron Barcelona

More Information

Additional Information:

Spanish association of Haematology This link exits the ClinicalTrials.gov site

Publications:

Sugawara T, Endo K, Shishido T, Sato A, Kameoka J, Fukuhara O, Yoshinaga K, Miura A. T cell-mediated inhibition of erythropoiesis in myelodysplastic syndromes. Am J Hematol. 1992 Dec;41(4):304-5. No abstract available.

Molldrem JJ, Jiang YZ, Stetler-Stevenson M, Mavroudis D, Hensel N, Barrett AJ. Haematological response of patients with myelodysplastic syndrome to antithymocyte globulin is associated with a loss of lymphocyte-mediated inhibition of CFU-GM and alterations in T-cell receptor Vbeta profiles. Br J Haematol. 1998 Sep;102(5):1314-22.

Smith MA, Smith JG. The occurrence subtype and significance of haemopoietic inhibitory T cells (HIT cells) in myelodysplasia: an in vitro study. Leuk Res. 1991;15(7):597-601.

Young NS. The problem of clonality in aplastic anemia: Dr Dameshek's riddle, restated. Blood. 1992 Mar 15;79(6):1385-92. Review. No abstract available.

Jonasova A, Neuwirtova R, Cermak J, Vozobulova V, Mocikova K, Siskova M, Hochova I. Cyclosporin A therapy in hypoplastic MDS patients and certain refractory anaemias without hypoplastic bone marrow. Br J Haematol. 1998 Feb;100(2):304-9.

Epperson DE, Nakamura R, Saunthararajah Y, Melenhorst J, Barrett AJ. Oligoclonal T cell expansion in myelodysplastic syndrome: evidence for an autoimmune process. Leuk Res. 2001 Dec;25(12):1075-83.

Maciejewski JP, Follmann D, Nakamura R, Saunthararajah Y, Rivera CE, Simonis T, Brown KE, Barrett JA, Young NS. Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome. Blood. 2001 Dec 15;98(13):3513-9.

Molldrem JJ, Caples M, Mavroudis D, Plante M, Young NS, Barrett AJ. Antithymocyte globulin for patients with myelodysplastic syndrome. Br J Haematol. 1997 Dec;99(3):699-705.

Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997 Mar 15;89(6):2079-88. Erratum in: Blood 1998 Feb 1;91(3):1100.

Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982 Jun;51(2):189-99.

Cheson BD, Bennett JM, Kantarjian H, Pinto A, Schiffer CA, Nimer SD, Lowenberg B, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Wijermans PW, Gore S, Greenberg PL; World Health Organization(WHO) international working group. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood. 2000 Dec 1;96(12):3671-4.

Cheson BD, Bennett JM, Kantarjian H, Schiffer CA, Nimer SD, Lowenberg B, Stone RM, Mittelman M, Sanz GF, Wijermans PW, Greenberg PL. Myelodysplastic syndromes standardized response criteria: further definition. Blood. 2001 Sep 15;98(6):1985. No abstract available.

Responsible Party:	Pethema, pethema
ClinicalTrials.gov Identifier:	NCT00488436 History of Changes
Other Study ID Numbers:	SMD/ATG-CSA/2002
Study First Received:	June 19, 2007
Last Updated:	November 17, 2008
Health Authority:	Spain:Spanish Ministry of Health

Keywords provided by PETHEMA Foundation:

Myelodysplastic Syndrome
Antithymocyte Globulin
Cyclosporine

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 May 21, 2013