Clinical trial NCT00488436: Antithymocyte Globulin and Cyclosporine in Treating Low Risk Patients With Myelodysplastic Syndrome
Official title: SMD/ATG-CSA: Antithymocyte Globulin and Cyclosporine in Treating Low Risk Patients With Myelodysplastic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Myelodysplastic Syndrome
Keywords: Myelodysplastic Syndrome
Antithymocyte Globulin
Cyclosporine
Lead sponsor: PETHEMA Foundation
Sponsor class: OTHER
First posted: 2007-06-20
Enrollment: 25
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Compare the efficacy and toxicity of antithymocyte globulin and cyclosporine in patients with low risk myelodysplastic syndrome
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Asturias
country: Spain
facility: Hospital de Cabueñes
city: Badalona
country: Spain
facility: Hospital germans Trias i Pujol
city: Bilbao
country: Spain
facility: Hospital de Basurto
city: Cartagena
country: Spain
facility: Hospital Ntra Sra del Rossell
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Materno Infantil de Las Palmas
city: Malaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Murcia
country: Spain
facility: Hospital Morales Messeguer
city: Pamplona
country: Spain
facility: Hospital de Navarra
city: Valencia
country: Spain
facility: Hospital Arnau de Vilanova
city: Valencia
country: Spain
facility: Hospital Dr Pesset
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario
Study officials:
affiliation: HOSPITAL LA FE VALENCIA
name: Sanz Guillermo, Dr
role: STUDY_DIRECTOR
affiliation: Hospital Vall d'Hebron Barcelona
name: Julia Antonio, Dr
role: STUDY_DIRECTOR
References:
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. doi: 10.1002/ajh.2830410425. No abstract available.
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. doi: 10.1046/j.1365-2141.1998.00920.x.
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. doi: 10.1016/0145-2126(91)90028-r.
citation: Young NS. The problem of clonality in aplastic anemia: Dr Dameshek's riddle, restated. Blood. 1992 Mar 15;79(6):1385-92. No abstract available.
citation: 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. doi: 10.1046/j.1365-2141.1998.00551.x.
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. doi: 10.1016/s0145-2126(01)00083-2.
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. doi: 10.1182/blood.v98.13.3513.
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. doi: 10.1046/j.1365-2141.1997.4423249.x.
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.
citation: 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.
citation: 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.
citation: 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. doi: 10.1182/blood.v98.6.1985. No abstract available.