Phase 2, Open-Label, Multi-Dose Study of Panhematin in Patients With MDS

Summary

This is a Phase II, open-label clinical trial examining the role of Panhematin® in patients with MDS. The objective of this study is to evaluate the safety and efficacy of Panhematin® (hematin for injection) in the treatment of adult patients (≥ 18 years of age) with low-risk MDS. The study will be conducted on an outpatient basis and will consist of the following: * A Screening Period (within 28 days of the Day 1) * Screening bone marrow aspiration and biopsy up to 60 days prior to receiving study medication * An 8-week Treatment Period (Days 1 through 4 of Week 1, and weekly visits during Weeks 2 through 8); partial and complete responders in any of the three cell lines may continue treatment for an additional 4 weeks * A 6-month Post treatment Follow-up Period (monthly clinic visits during Weeks 12 40)

Timeline

Start

2007-05

Primary completion

2008-12

Completion

2009-01

Publications

• Background Aul C, Germing U, Gattermann N, Minning H. Increasing incidence of myelodysplastic syndromes: real or fictitious? Leuk Res. 1998 Jan;22(1):93-100. doi: 10.1016/s0145-2126(97)00089-1.
• Background Aul C, Giagounidis A, Germing U. Epidemiological features of myelodysplastic syndromes: results from regional cancer surveys and hospital-based statistics. Int J Hematol. 2001 Jun;73(4):405-410. doi: 10.1007/BF02994001.
• Background Catenacci DV, Schiller GJ. Myelodysplasic syndromes: a comprehensive review. Blood Rev. 2005 Nov;19(6):301-19. doi: 10.1016/j.blre.2005.01.004.
• Background 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.
• Background Dhar GJ, Bossenmaier I, Cardinal R, Petryka ZJ, Watson CJ. Transitory renal failure following rapid administration of a relatively large amount of hematin in a patient with acute intermittent porphyria in clinical remission. Acta Med Scand. 1978;203(5):437-43. doi: 10.1111/j.0954-6820.1978.tb14903.x.
• Background Fibach E, Kollia P, Schechter AN, Noguchi CT, Rodgers GP. Hemin-induced acceleration of hemoglobin production in immature cultured erythroid cells: preferential enhancement of fetal hemoglobin. Blood. 1995 May 15;85(10):2967-74.
• Background 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.
• Background Mauritzson N, Albin M, Rylander L, Billstrom R, Ahlgren T, Mikoczy Z, Bjork J, Stromberg U, Nilsson PG, Mitelman F, Hagmar L, Johansson B. Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976-1993 and on 5098 unselected cases reported in the literature 1974-2001. Leukemia. 2002 Dec;16(12):2366-78. doi: 10.1038/sj.leu.2402713.
• Background McHale CM, Winter PC, Lappin TR. Erythroid gene expression is differentially regulated by erythropoietin, haemin and delta-aminolaevulinic acid in UT-7 cells. Br J Haematol. 1999 Mar;104(4):829-37. doi: 10.1046/j.1365-2141.1999.01269.x.
• Background Monette FC, Holden SA. Hemin enhances the in vitro growth of primitive erythroid progenitor cells. Blood. 1982 Aug;60(2):527-30.
• Background Panhematin® Product Prescribing Information. Abbott Laboratories, August 2000 Edition
• Background Porter PN, Meints RH, Mesner K. Enhancement of erythroid colony growth in culture by hemin. Exp Hematol. 1979 Jan;7(1):11-6.
• Background Rund D, Ben-Yehuda D. Therapy-related leukemia and myelodysplasia: evolving concepts of pathogenesis and treatment. Hematology. 2004 Jun;9(3):179-87. doi: 10.1080/10245330410001701503.
• Background Thompson JE, Luger SM. The role of hematopoietic stem cell transplantation in myelodysplastic syndrome. Oncology (Williston Park). 2005 Apr;19(4):533-42; discussion 542-4, 547-8.
• Background Timonen TT, Kauma H. Therapeutic effect of heme arginate in myelodysplastic syndromes. Eur J Haematol. 1992 Nov;49(5):234-8. doi: 10.1111/j.1600-0609.1992.tb00054.x.
• Background Volin L, Ruutu T, Knuutila S, Tenhunen R. Heme arginate treatment for myelodysplastic syndromes. Leuk Res. 1988;12(5):423-31. doi: 10.1016/0145-2126(88)90062-8.
• Background Williamson PJ, Kruger AR, Reynolds PJ, Hamblin TJ, Oscier DG. Establishing the incidence of myelodysplastic syndrome. Br J Haematol. 1994 Aug;87(4):743-5. doi: 10.1111/j.1365-2141.1994.tb06733.x.
• Background Vidaza® Product Prescribing Information. Pharmion Corporation, 5-18-04 Edition

Drugs

Indications