Combination of Ibuprofen, G-CSF and Plerixafor as Stem Cells Mobilization Regimen in Patients Affected by X-CGD

Summary

This is a phase II exploratory study conducted to evaluate the safety and efficacy of the combination of Ibuprofen, G-CSF and Plerixafor as stem cell mobilization regimen in patients affected by X-CGD.

Timeline

Start

2015-11-06

Primary completion

2023-07-13

Completion

2026-07-18

Publications

• Background Aiuti A, Bacchetta R, Seger R, Villa A, Cavazzana-Calvo M. Gene therapy for primary immunodeficiencies: Part 2. Curr Opin Immunol. 2012 Oct;24(5):585-91. doi: 10.1016/j.coi.2012.07.012. Epub 2012 Aug 18.
• Background Chiriaco M, Farinelli G, Capo V, Zonari E, Scaramuzza S, Di Matteo G, Sergi LS, Migliavacca M, Hernandez RJ, Bombelli F, Giorda E, Kajaste-Rudnitski A, Trono D, Grez M, Rossi P, Finocchi A, Naldini L, Gentner B, Aiuti A. Dual-regulated lentiviral vector for gene therapy of X-linked chronic granulomatosis. Mol Ther. 2014 Aug;22(8):1472-1483. doi: 10.1038/mt.2014.87. Epub 2014 May 29.
• Background Di Matteo G, Giordani L, Finocchi A, Ventura A, Chiriaco M, Blancato J, Sinibaldi C, Plebani A, Soresina A, Pignata C, Dellepiane RM, Trizzino A, Cossu F, Rondelli R, Rossi P, De Mattia D, Martire B; IPINET (Italian Network for Primary Immunodeficiencies). Molecular characterization of a large cohort of patients with Chronic Granulomatous Disease and identification of novel CYBB mutations: an Italian multicenter study. Mol Immunol. 2009 Jun;46(10):1935-41. doi: 10.1016/j.molimm.2009.03.016. Epub 2009 May 1.
• Background Edmonson JH, Hartmann LC, Long HJ, Colon-Otero G, Fitch TR, Jefferies JA, Braich TA, Maples WJ. Granulocyte-macrophage colony-stimulating factor. Preliminary observations on the influences of dose, schedule, and route of administration in patients receiving cyclophosphamide and carboplatin. Cancer. 1992 Nov 15;70(10):2529-39. doi: 10.1002/1097-0142(19921115)70:103.0.co;2-h.
• Background Gennery AR, Slatter MA, Grandin L, Taupin P, Cant AJ, Veys P, Amrolia PJ, Gaspar HB, Davies EG, Friedrich W, Hoenig M, Notarangelo LD, Mazzolari E, Porta F, Bredius RG, Lankester AC, Wulffraat NM, Seger R, Gungor T, Fasth A, Sedlacek P, Neven B, Blanche S, Fischer A, Cavazzana-Calvo M, Landais P; Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation; European Society for Immunodeficiency. Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: entering a new century, do we do better? J Allergy Clin Immunol. 2010 Sep;126(3):602-10.e1-11. doi: 10.1016/j.jaci.2010.06.015. Epub 2010 Jul 31.
• Background Grez M, Reichenbach J, Schwable J, Seger R, Dinauer MC, Thrasher AJ. Gene therapy of chronic granulomatous disease: the engraftment dilemma. Mol Ther. 2011 Jan;19(1):28-35. doi: 10.1038/mt.2010.232. Epub 2010 Nov 2.
• Background Gungor T, Teira P, Slatter M, Stussi G, Stepensky P, Moshous D, Vermont C, Ahmad I, Shaw PJ, Telles da Cunha JM, Schlegel PG, Hough R, Fasth A, Kentouche K, Gruhn B, Fernandes JF, Lachance S, Bredius R, Resnick IB, Belohradsky BH, Gennery A, Fischer A, Gaspar HB, Schanz U, Seger R, Rentsch K, Veys P, Haddad E, Albert MH, Hassan M; Inborn Errors Working Party of the European Society for Blood and Marrow Transplantation. Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study. Lancet. 2014 Feb 1;383(9915):436-48. doi: 10.1016/S0140-6736(13)62069-3. Epub 2013 Oct 23.
• Background Holland SM. Chronic granulomatous disease. Clin Rev Allergy Immunol. 2010 Feb;38(1):3-10. doi: 10.1007/s12016-009-8136-z.
• Background Hong KT, Kang HJ, Kim NH, Kim MS, Lee JW, Kim H, Park KD, Shin HY, Ahn HS. Successful mobilization using a combination of plerixafor and G-CSF in pediatric patients who failed previous chemomobilization with G-CSF alone and possible complications of the treatment. J Hematol Oncol. 2012 Mar 30;5:14. doi: 10.1186/1756-8722-5-14.
• Background Hoggatt J, Mohammad KS, Singh P, Hoggatt AF, Chitteti BR, Speth JM, Hu P, Poteat BA, Stilger KN, Ferraro F, Silberstein L, Wong FK, Farag SS, Czader M, Milne GL, Breyer RM, Serezani CH, Scadden DT, Guise TA, Srour EF, Pelus LM. Differential stem- and progenitor-cell trafficking by prostaglandin E2. Nature. 2013 Mar 21;495(7441):365-9. doi: 10.1038/nature11929. Epub 2013 Mar 13.
• Background Kang EM, Choi U, Theobald N, Linton G, Long Priel DA, Kuhns D, Malech HL. Retrovirus gene therapy for X-linked chronic granulomatous disease can achieve stable long-term correction of oxidase activity in peripheral blood neutrophils. Blood. 2010 Jan 28;115(4):783-91. doi: 10.1182/blood-2009-05-222760. Epub 2009 Dec 1.
• Background Kang HJ, Bartholomae CC, Paruzynski A, Arens A, Kim S, Yu SS, Hong Y, Joo CW, Yoon NK, Rhim JW, Kim JG, Von Kalle C, Schmidt M, Kim S, Ahn HS. Retroviral gene therapy for X-linked chronic granulomatous disease: results from phase I/II trial. Mol Ther. 2011 Nov;19(11):2092-101. doi: 10.1038/mt.2011.166. Epub 2011 Aug 30.
• Background Martinez CA, Shah S, Shearer WT, Rosenblatt HM, Paul ME, Chinen J, Leung KS, Kennedy-Nasser A, Brenner MK, Heslop HE, Liu H, Wu MF, Hanson IC, Krance RA. Excellent survival after sibling or unrelated donor stem cell transplantation for chronic granulomatous disease. J Allergy Clin Immunol. 2012 Jan;129(1):176-83. doi: 10.1016/j.jaci.2011.10.005. Epub 2011 Nov 12.
• Background Ott MG, Schmidt M, Schwarzwaelder K, Stein S, Siler U, Koehl U, Glimm H, Kuhlcke K, Schilz A, Kunkel H, Naundorf S, Brinkmann A, Deichmann A, Fischer M, Ball C, Pilz I, Dunbar C, Du Y, Jenkins NA, Copeland NG, Luthi U, Hassan M, Thrasher AJ, Hoelzer D, von Kalle C, Seger R, Grez M. Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nat Med. 2006 Apr;12(4):401-9. doi: 10.1038/nm1393. Epub 2006 Apr 2.
• Background Panch SR, Yau YY, Kang EM, De Ravin SS, Malech HL, Leitman SF. Mobilization characteristics and strategies to improve hematopoietic progenitor cell mobilization and collection in patients with chronic granulomatous disease and severe combined immunodeficiency. Transfusion. 2015 Feb;55(2):265-74. doi: 10.1111/trf.12830. Epub 2014 Aug 21.
• Background Pham HP, Patel N, Semedei-Pomales M, Bhatia M, Schwartz J. The use of plerixafor in hematopoietic progenitor cell collection in pediatric patients: a single center experience. Cytotherapy. 2012 Apr;14(4):467-72. doi: 10.3109/14653249.2012.658912. Epub 2012 Feb 20.
• Background Roos D, Kuhns DB, Maddalena A, Bustamante J, Kannengiesser C, de Boer M, van Leeuwen K, Koker MY, Wolach B, Roesler J, Malech HL, Holland SM, Gallin JI, Stasia MJ. Hematologically important mutations: the autosomal recessive forms of chronic granulomatous disease (second update). Blood Cells Mol Dis. 2010 Apr 15;44(4):291-9. doi: 10.1016/j.bcmd.2010.01.009. Epub 2010 Feb 18.
• Background Sevilla J, Schiavello E, Madero L, Pardeo M, Guggiari E, Baragano M, Luksch R, Massimino M. Priming of hematopoietic progenitor cells by plerixafor and filgrastim in children with previous failure of mobilization with chemotherapy and/or cytokine treatment. J Pediatr Hematol Oncol. 2012 Mar;34(2):146-50. doi: 10.1097/MPH.0b013e31821c2cb8.
• Background Seger RA. Modern management of chronic granulomatous disease. Br J Haematol. 2008 Feb;140(3):255-66. doi: 10.1111/j.1365-2141.2007.06880.x.
• Background Santilli G, Almarza E, Brendel C, Choi U, Beilin C, Blundell MP, Haria S, Parsley KL, Kinnon C, Malech HL, Bueren JA, Grez M, Thrasher AJ. Biochemical correction of X-CGD by a novel chimeric promoter regulating high levels of transgene expression in myeloid cells. Mol Ther. 2011 Jan;19(1):122-32. doi: 10.1038/mt.2010.226. Epub 2010 Oct 26.
• Background Seger RA. Chronic granulomatous disease: recent advances in pathophysiology and treatment. Neth J Med. 2010 Nov;68(11):334-40.
• Background Son MH, Kang ES, Kim DH, Lee SH, Yoo KH, Sung KW, Koo HH, Kim DW, Kim JY, Cho EJ. Efficacy and toxicity of plerixafor for peripheral blood stem cell mobilization in children with high-risk neuroblastoma. Pediatr Blood Cancer. 2013 Aug;60(8):E57-9. doi: 10.1002/pbc.24506. Epub 2013 Mar 4.
• Background Stein S, Ott MG, Schultze-Strasser S, Jauch A, Burwinkel B, Kinner A, Schmidt M, Kramer A, Schwable J, Glimm H, Koehl U, Preiss C, Ball C, Martin H, Gohring G, Schwarzwaelder K, Hofmann WK, Karakaya K, Tchatchou S, Yang R, Reinecke P, Kuhlcke K, Schlegelberger B, Thrasher AJ, Hoelzer D, Seger R, von Kalle C, Grez M. Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease. Nat Med. 2010 Feb;16(2):198-204. doi: 10.1038/nm.2088. Epub 2010 Jan 24.
• Background Yannaki E, Karponi G, Zervou F, Constantinou V, Bouinta A, Tachynopoulou V, Kotta K, Jonlin E, Papayannopoulou T, Anagnostopoulos A, Stamatoyannopoulos G. Hematopoietic stem cell mobilization for gene therapy: superior mobilization by the combination of granulocyte-colony stimulating factor plus plerixafor in patients with beta-thalassemia major. Hum Gene Ther. 2013 Oct;24(10):852-60. doi: 10.1089/hum.2013.163.
• Background Yannaki E, Papayannopoulou T, Jonlin E, Zervou F, Karponi G, Xagorari A, Becker P, Psatha N, Batsis I, Kaloyannidis P, Tahynopoulou V, Constantinou V, Bouinta A, Kotta K, Athanassiadou A, Anagnostopoulos A, Fassas A, Stamatoyannopoulos G. Hematopoietic stem cell mobilization for gene therapy of adult patients with severe beta-thalassemia: results of clinical trials using G-CSF or plerixafor in splenectomized and nonsplenectomized subjects. Mol Ther. 2012 Jan;20(1):230-8. doi: 10.1038/mt.2011.195. Epub 2011 Sep 27.
• Background Wu C, Dunbar CE. Stem cell gene therapy: the risks of insertional mutagenesis and approaches to minimize genotoxicity. Front Med. 2011 Dec;5(4):356-71. doi: 10.1007/s11684-011-0159-1. Epub 2011 Dec 27.

Drugs

Indications