AlloHCT With PegINFa for Myelofibrosis

Summary

This is a single site, open-label, dose de-escalation, Phase 1 study of pegylated interferon alfa-2a administered after alloHCT in subjects with primary or secondary myelofibrosis. Part 1 of the study will assess the rate of dose-limiting toxicities (DLTs) during the DLT evaluation period and identify the Recommended Phase 2 Dose (RP2D). Once the RP2D is identified, 6 additional patients will be enrolled in the expansion cohort.

Timeline

Start

2023-08-02

Primary completion

2026-08

Completion

2028-03

Publications

• Background Mesa RA, Silverstein MN, Jacobsen SJ, Wollan PC, Tefferi A. Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted County Study, 1976-1995. Am J Hematol. 1999 May;61(1):10-5. doi: 10.1002/(sici)1096-8652(199905)61:13.0.co;2-i.
• Background Tefferi A. Primary myelofibrosis: 2019 update on diagnosis, risk-stratification and management. Am J Hematol. 2018 Dec;93(12):1551-1560. doi: 10.1002/ajh.25230. Epub 2018 Oct 26.
• Background Ballen KK, Shrestha S, Sobocinski KA, Zhang MJ, Bashey A, Bolwell BJ, Cervantes F, Devine SM, Gale RP, Gupta V, Hahn TE, Hogan WJ, Kroger N, Litzow MR, Marks DI, Maziarz RT, McCarthy PL, Schiller G, Schouten HC, Roy V, Wiernik PH, Horowitz MM, Giralt SA, Arora M. Outcome of transplantation for myelofibrosis. Biol Blood Marrow Transplant. 2010 Mar;16(3):358-67. doi: 10.1016/j.bbmt.2009.10.025. Epub 2009 Oct 30.
• Background Patriarca F, Bacigalupo A, Sperotto A, Isola M, Soldano F, Bruno B, van Lint MT, Iori AP, Santarone S, Porretto F, Pioltelli P, Visani G, Iacopino P, Fanin R, Bosi A; GITMO. Allogeneic hematopoietic stem cell transplantation in myelofibrosis: the 20-year experience of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Haematologica. 2008 Oct;93(10):1514-22. doi: 10.3324/haematol.12828. Epub 2008 Aug 25.
• Background Gupta V, Malone AK, Hari PN, Ahn KW, Hu ZH, Gale RP, Ballen KK, Hamadani M, Olavarria E, Gerds AT, Waller EK, Costa LJ, Antin JH, Kamble RT, van Besien KM, Savani BN, Schouten HC, Szer J, Cahn JY, de Lima MJ, Wirk B, Aljurf MD, Popat U, Bejanyan N, Litzow MR, Norkin M, Lewis ID, Hale GA, Woolfrey AE, Miller AM, Ustun C, Jagasia MH, Lill M, Maziarz RT, Cortes J, Kalaycio ME, Saber W. Reduced-intensity hematopoietic cell transplantation for patients with primary myelofibrosis: a cohort analysis from the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2014 Jan;20(1):89-97. doi: 10.1016/j.bbmt.2013.10.018. Epub 2013 Oct 23.
• Background Slot S, Smits K, van de Donk NW, Witte BI, Raymakers R, Janssen JJ, Broers AE, Te Boekhorst PA, Zweegman S. Effect of conditioning regimens on graft failure in myelofibrosis: a retrospective analysis. Bone Marrow Transplant. 2015 Nov;50(11):1424-31. doi: 10.1038/bmt.2015.172. Epub 2015 Aug 3.
• Background Chhabra S, Narra RK, Wu R, Szabo A, George G, Michaelis LC, D'Souza A, Dhakal B, Drobyski WR, Fenske TS, Jerkins JH, Pasquini MC, Rizzo RD, Saber W, Shah NN, Shaw BE, Hamadani M, Hari PN. Fludarabine/Busulfan Conditioning-Based Allogeneic Hematopoietic Cell Transplantation for Myelofibrosis: Role of Ruxolitinib in Improving Survival Outcomes. Biol Blood Marrow Transplant. 2020 May;26(5):893-901. doi: 10.1016/j.bbmt.2020.01.010. Epub 2020 Jan 23.
• Background Guardiola P, Anderson JE, Bandini G, Cervantes F, Runde V, Arcese W, Bacigalupo A, Przepiorka D, O'Donnell MR, Polchi P, Buzyn A, Sutton L, Cazals-Hatem D, Sale G, de Witte T, Deeg HJ, Gluckman E. Allogeneic stem cell transplantation for agnogenic myeloid metaplasia: a European Group for Blood and Marrow Transplantation, Societe Francaise de Greffe de Moelle, Gruppo Italiano per il Trapianto del Midollo Osseo, and Fred Hutchinson Cancer Research Center Collaborative Study. Blood. 1999 May 1;93(9):2831-8.
• Background Jacobson RJ, Salo A, Fialkow PJ. Agnogenic myeloid metaplasia: a clonal proliferation of hematopoietic stem cells with secondary myelofibrosis. Blood. 1978 Feb;51(2):189-94.
• Background Ianotto JC, Chauveau A, Boyer-Perrard F, Gyan E, Laribi K, Cony-Makhoul P, Demory JL, de Renzis B, Dosquet C, Rey J, Roy L, Dupriez B, Knoops L, Legros L, Malou M, Hutin P, Ranta D, Benbrahim O, Ugo V, Lippert E, Kiladjian JJ. Benefits and pitfalls of pegylated interferon-alpha2a therapy in patients with myeloproliferative neoplasm-associated myelofibrosis: a French Intergroup of Myeloproliferative neoplasms (FIM) study. Haematologica. 2018 Mar;103(3):438-446. doi: 10.3324/haematol.2017.181297. Epub 2017 Dec 7.
• Background Wang X, Ye F, Tripodi J, Hu CS, Qiu J, Najfeld V, Novak J, Li Y, Rampal R, Hoffman R. JAK2 inhibitors do not affect stem cells present in the spleens of patients with myelofibrosis. Blood. 2014 Nov 6;124(19):2987-95. doi: 10.1182/blood-2014-02-558015. Epub 2014 Sep 5.
• Background Pizzi M, Silver RT, Barel A, Orazi A. Recombinant interferon-alpha in myelofibrosis reduces bone marrow fibrosis, improves its morphology and is associated with clinical response. Mod Pathol. 2015 Oct;28(10):1315-23. doi: 10.1038/modpathol.2015.93. Epub 2015 Aug 14.
• Background Liu E, Jelinek J, Pastore YD, Guan Y, Prchal JF, Prchal JT. Discrimination of polycythemias and thrombocytoses by novel, simple, accurate clonality assays and comparison with PRV-1 expression and BFU-E response to erythropoietin. Blood. 2003 Apr 15;101(8):3294-301. doi: 10.1182/blood-2002-07-2287. Epub 2002 Dec 19.
• Background King KY, Matatall KA, Shen CC, Goodell MA, Swierczek SI, Prchal JT. Comparative long-term effects of interferon alpha and hydroxyurea on human hematopoietic progenitor cells. Exp Hematol. 2015 Oct;43(10):912-918.e2. doi: 10.1016/j.exphem.2015.05.013. Epub 2015 Jun 11.
• Background Xiong Z, Liu E, Yan Y, Silver RT, Yang F, Chen IH, Chen Y, Verstovsek S, Wang H, Prchal J, Yang XF. An unconventional antigen translated by a novel internal ribosome entry site elicits antitumor humoral immune reactions. J Immunol. 2006 Oct 1;177(7):4907-16. doi: 10.4049/jimmunol.177.7.4907.
• Background Xiong Z, Yan Y, Liu E, Silver RT, Verstovsek S, Yang F, Wang H, Prchal J, Yang XF. Novel tumor antigens elicit anti-tumor humoral immune reactions in a subset of patients with polycythemia vera. Clin Immunol. 2007 Mar;122(3):279-87. doi: 10.1016/j.clim.2006.10.006. Epub 2006 Nov 17.
• Background Xiong Z, Liu E, Yan Y, Silver RT, Yang F, Chen IH, Hodge I, Verstovsek S, Segura FJ, Wang H, Prchal J, Yang XF. A novel unconventional antigen MPD5 elicits anti-tumor humoral immune responses in a subset of patients with polycythemia vera. Int J Immunopathol Pharmacol. 2007 Apr-Jun;20(2):373-80. doi: 10.1177/039463200702000218.
• Background Gilbert HS. Long term treatment of myeloproliferative disease with interferon-alpha-2b: feasibility and efficacy. Cancer. 1998 Sep 15;83(6):1205-13. doi: 10.1002/(sici)1097-0142(19980915)83:63.0.co;2-8.
• Background Magenau JM, Pawarode A, Riwes MM, et al: A Phase I/II Clinical Trial of Type 1 Interferon for Reduction of Relapse after HCT in High Risk AML. Biology of Blood and Marrow Transplantation 25:S12-S13, 2019
• Background Mesa RA, Li CY, Ketterling RP, Schroeder GS, Knudson RA, Tefferi A. Leukemic transformation in myelofibrosis with myeloid metaplasia: a single-institution experience with 91 cases. Blood. 2005 Feb 1;105(3):973-7. doi: 10.1182/blood-2004-07-2864. Epub 2004 Sep 23.
• Background Jain AG, Gerds AT. How I treat anemia in myelofibrosis. Blood. 2025 Apr 17;145(16):1738-1746. doi: 10.1182/blood.2023022414.
• Background Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.

Drugs

Indications