Antithymocyte Globulin and Cyclosporine in Treating Low Risk Patients With Myelodysplastic Syndrome

Myelodysplastic Syndrome Clinical Trial

Official title:

SMD/ATG-CSA: Antithymocyte Globulin and Cyclosporine in Treating Low Risk Patients With Myelodysplastic Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00488436
• Other study ID #: SMD/ATG-CSA/2002
• Status: Completed
• Phase: Phase 4
• First received: June 19, 2007
• Last updated: November 17, 2008
• Start date: May 2002
• Est. completion date: December 2007

Study information

• Verified date: November 2008
• Source: PETHEMA Foundation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain:Spanish Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: December 2007
• Est. primary completion date: June 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Antithymocyte globulin

• Cyclosporine

Locations

Country	Name	City	State
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 Arnau de Vilanova	Valencia
Spain	Hospital Dr Pesset	Valencia
Spain	Hospital Clinico Universitario	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
PETHEMA Foundation

Country where clinical trial is conducted

Spain, 

References & Publications (12)

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. — View Citation

Cheson BD, Bennett JM, Kantarjian H, Pinto A, Schiffer CA, Nimer SD, Löwenberg 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. — View Citation

Cheson BD, Bennett JM, Kantarjian H, Schiffer CA, Nimer SD, Löwenberg 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. — View Citation

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. — View Citation

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. — View Citation

Jonásova A, Neuwirtová R, Cermák J, Vozobulová V, Mociková K, Sisková M, Hochová 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Young NS. The problem of clonality in aplastic anemia: Dr Dameshek's riddle, restated. Blood. 1992 Mar 15;79(6):1385-92. Review. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare the efficacy and toxicity of antithymocyte globulin and cyclosporine in patients with low risk myelodysplastic syndrome		3 years

External Links

•   Pethema Foundation web
•   Spanish association of Haematology