A phase 2 randomized dose-ranging study of the JAK2-selective inhibitor fedratinib (SAR302503) in patients with myelofibrosis

Blood Cancer Journal

Volumn 5, Issue 8, 2015, Pages

  Pardanani, A ^a   Tefferi, A ^a   Jamieson, C ^b   Gabrail, N ^c   Lebedinsky, C ^d   Gao, G ^d   Liu, F ^d   Xu, C ^d   Cao, H ^d   Talpaz, M ^e  

^a MAYO CLINIC   (United States)

^b UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^c Gabrail Cancer Center   (United States)

^d Sanofi ^*  (United States)

^e UNIVERSITY OF MICHIGAN HOSPITALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; AMYLASE; ASPARTATE AMINOTRANSFERASE; BILIRUBIN; CREATININE; FEDRATINIB; JANUS KINASE 2; STAT3 PROTEIN; TRIACYLGLYCEROL LIPASE; ANTINEOPLASTIC AGENT; CYTOKINE; JAK2 PROTEIN, HUMAN; PYRROLIDINE DERIVATIVE; SULFONAMIDE;

ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALLELE; AMYLASE BLOOD LEVEL; ANEMIA; AREA UNDER THE CURVE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; BILIRUBIN BLOOD LEVEL; CLINICAL ARTICLE; CONSTIPATION; CONTROLLED STUDY; CREATININE BLOOD LEVEL; DIARRHEA; DRUG ACCUMULATION; DRUG DOSE REDUCTION; DRUG SAFETY; DRUG WITHDRAWAL; DYSPNEA; FATIGUE; FEMALE; HUMAN; LEUKOCYTOSIS; LIMB PAIN; LIVER FAILURE; MALE; MAXIMUM PLASMA CONCENTRATION; MULTIPLE CYCLE TREATMENT; MYELOFIBROSIS; NAUSEA; PERIPHERAL EDEMA; PHARMACODYNAMICS; PHASE 2 CLINICAL TRIAL; PROTEIN PHOSPHORYLATION; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SPLEEN SIZE; STEADY STATE; THROMBOCYTOPENIA; TREATMENT DURATION; TREATMENT RESPONSE; TRIACYLGLYCEROL LIPASE BLOOD LEVEL; VOMITING; WERNICKE ENCEPHALOPATHY; ANTAGONISTS AND INHIBITORS; BLOOD; CLINICAL TRIAL; DOSE RESPONSE; DRUG EFFECTS; GENE FREQUENCY; GENETICS; MIDDLE AGED; MISSENSE MUTATION; MULTICENTER STUDY; PRIMARY MYELOFIBROSIS; SPLEEN; TREATMENT OUTCOME; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS; CYTOKINES; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; GENE FREQUENCY; HUMANS; JANUS KINASE 2; MALE; MIDDLE AGED; MUTATION, MISSENSE; PRIMARY MYELOFIBROSIS; PYRROLIDINES; SPLEEN; SULFONAMIDES; TREATMENT OUTCOME;

EID: 84975231524     PISSN: None     EISSN: 20445385     Source Type: Journal    
DOI: 10.1038/bcj.2015.63     Document Type: Article

References (32)

1. Vannucchi AM, Guglielmelli P, Tefferi A. Advances in understanding and management of myeloproliferative neoplasms. CA Cancer J Clin 2009; 59: 171-191.
2. Levine RL, Gilliland DG. Myeloproliferative disorders. Blood 2008; 112: 2190-2198.
3. Tefferi A. Myelofibrosis with myeloid metaplasia. N Engl J Med 2000; 342: 1255-1265.
4. Tefferi A. JAK inhibitors for myeloproliferative neoplasms: clarifying facts from myths. Blood 2012; 119: 2721-2730.
5. Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 2009; 113: 2895-2901.
6. Levine RL, Pardanani A, Tefferi A, Gilliland DG. Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders. Nat Rev Cancer 2007; 7: 673-683.
7. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR et al. A gain-offunction mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005; 352: 1779-1790.
8. Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005; 365: 1054-1061.
9. James C, Ugo V, Le Couédic JP, Staerk J, Delhommeau F, Lacout C et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005; 434: 1144-1148.
10. Pardanani A, Lasho TL, Finke CM, Tefferi A. Infrequent occurrence of MPL exon 10 mutations in polycythemia vera and post-polycythemia vera myelofibrosis. Am J Hematol 2011; 86: 701-702.
11. Pikman Y, Lee B, Mercher T, McDowell E, Ebert BL, Gozo M et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PloS Med 2006; 3: e270.
12. Guglielmelli P, Pancrazzi A, Bergamaschi G, Rosti V, Villani L, Antonioli E et al. Anaemia characterises patients with myelofibrosis harbouring Mpl mutation. Br J Haematol 2007; 137: 244-247.
13. Wernig G, Mercher T, Okabe R, Levine RL, Lee BH, Gilliland DG. Expression of Jak2V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow transplant. Blood 2006; 107: 4274-4281.
14. Hasselbalch HC. The role of cytokines in the initiation and progression of myelofibrosis. Cytokine Growth Factor Rev 2013; 24: 133-145.
15. Verstosvek S, Mesa R, Gotlib J, Levy RS, Gupta V, DiPersio JF et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. NEnglJMed2012; 366: 799-807.
16. Harrison C, Kiladjian J, Al-Ali H, Gisslinger H, Waltzman R, Stalbovskaya V et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. NEngl J Med 2012; 366: 787-798.
17. Lasho TL, Tefferi A, Hood JD, Verstosvek S, Gilliland DG, Pardanani A. TG101348, a JAK2-selective antagonist, inhibits primary hematopoietic cells derived from myeloproliferative disorder patients with JAK2V617F, MPLW515K or JAK2 exon 12 mutations as well as mutation negative patients. Leukemia 2008; 22: 1790-1792.
18. Geron I, Abrahamsson AE, Barroga CF, Kavalerchik E, Gotlib J, Hood JD et al. Selective inhibition of JAK2-driven erythroid differentiation of polycythemia vera progenitors. Cancer Cell 2008; 13: 321-330.
19. Wernig G, Kharas MG, Okabe R, Moore SA, Leeman DS, Cullen DE et al. Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. Cancer Cell 2008; 13: 311-320.
20. Pardanani A, Gotlib JR, Jamieson C, Cortes JE, Talpaz M, Stone RM et al. Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis. J Clin Oncol 2011; 29: 789-796.
21. Gotlib J, Pardanani A, Jamieson C, Cortes J, Talpaz M, Stone R et al. Long-term follow-up of a phase 1/2 study of SAR302503, an oral JAK2 selective inhibitor, in patients with myelofibrosis (MF). Haematologica 2012; 97, Abstract 0361.
22. Vardimann JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A et al. The2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009; 114: 937-951.
23. Scherber R, Dueck AC, Johansson P, Barbui T, Barosi G, Vannucchi AM et al. The myeloproliferative neoplasm symptom assessment form; international prospective validation and reliability trial in 402 patients. Blood 2011; 118: 401-408.
24. EuroQol Group. EQ-5DTM . Available at http://www.euroqol.org/home.html. Accessed 19 December 2013.
25. Mendoza TR, Wang XS, Cleeland MS, Morrissey M, Johnson BA, Wendt JK. The rapid assessment of fatigue severity in cancer patients: use of the Brief Fatigue Inventory. Cancer 1999; 85: 1186-1196.
26. Lui F, Talpaz M, Pardanani A, Jamieson C, Gabrail N, Tefferi A et al. Determination of JAK2V617F allele burden reduction in a Phase 2 study of patients with myelofibrosis treated with SAR302503 using a sensitive and robust allele-specific qPCR assay. American Association of Cancer Research, 6-10 April 2013; Washington, DC, USA. Abstract No. LB-294.
27. Jovanovic JV, Ivey A, Vannucchi AM, Lippert E, Oppliger Leibundgut E, Cassinat B et al. Establishing optimal quantitative-polymerase chain reaction assays for routine diagnosis and tracking of minimal residual disease in JAK2-V617Fassociated myeloproliferative neoplasms: a joint European LeukemiaNet/ MPN&MPNr-EuroNet (COST action BM0902) study. Leukemia 2013; 27: 2032-2039.
28. Harrison CN, Kiladjian J, Gisslinger H, Passamonti F, Sirulnik A, Wang L et al. Association of cytokine levels and reductions in spleen size in COMFORT-II: a phase 3 study comparing ruxolitinib with best available therapy (BAT). Haematologica 2012; 97, Abstract No. 0379.
29. Fleischman AG, Aichberger KJ, Luty SB, Bumm TG, Petersen CL, Doratotaj S et al. TNFα facilitates clonal expansion of JAK2V167F positive cells in myeloproliferative neoplasms. Blood 2011; 118: 6392-6398.
30. Krenning G, Moonen JR, Harmsen MC. Pleiotropism of adiponectin: inflammation, neovascularization, and fibrosis. Circ Res 2009; 104: 1029-1031.
31. Fang F, Liu L, Yang Y, Tamaki Z, Wei J, Marangoni RG et al. The adipokine adiponectin has potent anti-fibrotic effects mediated via adenosine monophosphate-activated protein kinase: novel target for fibrosis therapy. Arthritis Res Ther 2012; 14: R229.
32. Gale RP, Barosi G, Barbui T, Cervantes F, Dohner K, Dupriez B et al. What are RBCtransfusion-dependence and independence? Leuk Res 2011; 35: 8-11.