Reduced-intensity Immunoablation and Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for Multiple Sclerosis

Multiple Sclerosis Clinical Trial

Official title:

Evaluation of the Safety and Efficacy of Reduced-intensity Immunoablation and Autologous Hematopoietic Stem Cell Transplantation (AHSCT) in Multiple Sclerosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03113162
• Other study ID #: MMCIRB 2015-024
• Status: Recruiting
• Phase: Phase 1
• First received: April 10, 2017
• Last updated: May 3, 2017
• Start date: May 29, 2015
• Est. completion date: May 29, 2022

Study information

• Verified date: May 2017
• Source: Makati Medical Center
• Contact: Marviel T Berboso, RN
• Phone: 8888999
• Email: Inquiry.CTC[@]makatimed.net.ph
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a patient-sponsored study that evaluates the safety and efficacy of reduced-intensity immunoablation followed by a single dose autologous hematopoetic stem cell transplantation in patients diagnosed with multiple sclerosis. Patients are followed-up after 1 month, 3 months, 6 months and 12 months post-transplantation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: May 29, 2022
• Est. primary completion date: May 29, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Diagnosed with progressive multiple sclerosis with or without relapses

• EDSS score between 1.5 and 7.0, including documented rapid progression over the previous year unresponsive to conventional therapies or no available treatment options

• Aged between 18 and 60 with a history of at least one enhancing lesion on brain MRI

• With absolute neutrophil count = 1,000/mm^3, platelet count = 100,000/mm^3 and hemoglobin = 9.0 g/dL

Exclusion Criteria:

• Patients with cardiac, renal, pulmonary, hepatic, or other organ impairment that would limit their ability to receive dose-intensive immunosuppressive therapy, high-dose chemotherapy, and/or Autologous HSCT

• Patients with any active or chronic infection e.g. uncontrolled viral, fungal, or bacterial infection

• Uncontrolled diabetes

• Patients who are seropositive for HIV1, HIV2, Hepatitis B Surface Antigen, and Hepatitis C

• Patients whose life expectancy is severely limited by another illness

• Patients with evidence of myelodysplasia or other non-autoimmune cytopenia

• Patients having received a cytotoxic agent within one month prior to this study

• Patients who are pregnant or at risk of pregnancy, including those unwilling to practice

• Patients with psychiatric illness, mental deficiency, or cognitive dysfunction

• Patients unable to give written informed consent in accordance with research ethics board guidelines

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Biological:
• Autologous Hematopoietic Stem Cell

Drug:
• BEAM Regimen
Reduced-intensity BEAM for Immunoablation

Locations

Country	Name	City	State
Philippines	Makati Medical Center	Makati

Sponsors (1)

Lead Sponsor	Collaborator
Makati Medical Center

Country where clinical trial is conducted

Philippines, 

References & Publications (21)

Akkök CA, Liseth K, Hervig T, Ryningen A, Bruserud Ø, Ersvaer E. Use of different DMSO concentrations for cryopreservation of autologous peripheral blood stem cell grafts does not have any major impact on levels of leukocyte- and platelet-derived soluble mediators. Cytotherapy. 2009;11(6):749-60. doi: 10.3109/14653240902980443. — View Citation

Appelbaum FR, Bacigalupo A, Soiffer R. Anti-T cell antibodies as part of the preparative regimen in hematopoietic cell transplantation--a debate. Biol Blood Marrow Transplant. 2012 Jan;18(1 Suppl):S111-5. doi: 10.1016/j.bbmt.2011.11.002. Review. — View Citation

Brück W. The pathology of multiple sclerosis is the result of focal inflammatory demyelination with axonal damage. J Neurol. 2005 Nov;252 Suppl 5:v3-9. Review. — View Citation

Burt RK, Balabanov R, Han X, Sharrack B, Morgan A, Quigley K, Yaung K, Helenowski IB, Jovanovic B, Spahovic D, Arnautovic I, Lee DC, Benefield BC, Futterer S, Oliveira MC, Burman J. Association of nonmyeloablative hematopoietic stem cell transplantation with neurological disability in patients with relapsing-remitting multiple sclerosis. JAMA. 2015 Jan 20;313(3):275-84. doi: 10.1001/jama.2014.17986. — View Citation

Burt RK, Loh Y, Cohen B, Stefoski D, Balabanov R, Katsamakis G, Oyama Y, Russell EJ, Stern J, Muraro P, Rose J, Testori A, Bucha J, Jovanovic B, Milanetti F, Storek J, Voltarelli JC, Burns WH. Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study. Lancet Neurol. 2009 Mar;8(3):244-53. doi: 10.1016/S1474-4422(09)70017-1. Epub 2009 Jan 29. Erratum in: Lancet Neurol. 2009 Apr;8(4):309. Stefosky, Dusan [corrected to Stefoski, Dusan]. — View Citation

Cabezudo E, Dalmases C, Ruz M, Sanchez JA, Torrico C, Sola C, Querol S, García J. Leukapheresis components may be cryopreserved at high cell concentrations without additional loss of HPC function. Transfusion. 2000 Oct;40(10):1223-7. — View Citation

Costantino CM, Baecher-Allan C, Hafler DA. Multiple sclerosis and regulatory T cells. J Clin Immunol. 2008 Nov;28(6):697-706. doi: 10.1007/s10875-008-9236-x. Epub 2008 Sep 2. Review. — View Citation

De Boer F, Dräger AM, Van der Wall E, Pinedo HM, Schuurhuis GJ. Changes in L-selectin expression on CD34-positive cells upon cryopreservation of peripheral blood stem cell transplants. Bone Marrow Transplant. 1998 Dec;22(11):1103-10. — View Citation

Farge D, Labopin M, Tyndall A, Fassas A, Mancardi GL, Van Laar J, Ouyang J, Kozak T, Moore J, Kötter I, Chesnel V, Marmont A, Gratwohl A, Saccardi R. Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years' experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases. Haematologica. 2010 Feb;95(2):284-92. doi: 10.3324/haematol.2009.013458. Epub 2009 Sep 22. — View Citation

Fassas A, Anagnostopoulos A, Kazis A, Kapinas K, Sakellari I, Kimiskidis V, Tsompanakou A. Peripheral blood stem cell transplantation in the treatment of progressive multiple sclerosis: first results of a pilot study. Bone Marrow Transplant. 1997 Oct;20(8):631-8. — View Citation

Fassas A, Kimiskidis VK. Autologous hemopoietic stem cell transplantation in the treatment of multiple sclerosis: rationale and clinical experience. J Neurol Sci. 2004 Aug 15;223(1):53-8. Review. — View Citation

Frischer JM, Bramow S, Dal-Bianco A, Lucchinetti CF, Rauschka H, Schmidbauer M, Laursen H, Sorensen PS, Lassmann H. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain. 2009 May;132(Pt 5):1175-89. doi: 10.1093/brain/awp070. Epub 2009 Mar 31. — View Citation

Iannalfi A, Bambi F, Tintori V, Lacitignola L, Bernini G, Mariani MP, Sanvito MC, Pagliai F, Brandigi F, Muscarella E, Tapinassi F, Faulkner L. Peripheral blood progenitor uncontrolled-rate freezing: a single pediatric center experience. Transfusion. 2007 Dec;47(12):2202-6. Epub 2007 Aug 21. — View Citation

Mancardi GL, Sormani MP, Gualandi F, Saiz A, Carreras E, Merelli E, Donelli A, Lugaresi A, Di Bartolomeo P, Rottoli MR, Rambaldi A, Amato MP, Massacesi L, Di Gioia M, Vuolo L, Currò D, Roccatagliata L, Filippi M, Aguglia U, Iacopino P, Farge D, Saccardi R; ASTIMS Haemato-Neurological Collaborative Group, On behalf of the Autoimmune Disease Working Party (ADWP) of the European Group for Blood and Marrow Transplantation (EBMT).; ASTIMS Haemato-Neurological Collaborative Group On behalf of the Autoimmune Disease Working Party ADWP of the European Group for Blood and Marrow Transplantation EBMT.. Autologous hematopoietic stem cell transplantation in multiple sclerosis: a phase II trial. Neurology. 2015 Mar 10;84(10):981-8. doi: 10.1212/WNL.0000000000001329. Epub 2015 Feb 11. — View Citation

Passweg JR, Baldomero H, Bregni M, Cesaro S, Dreger P, Duarte RF, Falkenburg JH, Kröger N, Farge-Bancel D, Gaspar HB, Marsh J, Mohty M, Peters C, Sureda A, Velardi A, Ruiz de Elvira C, Madrigal A; European Group for Blood and Marrow Transplantation.. Hematopoietic SCT in Europe: data and trends in 2011. Bone Marrow Transplant. 2013 Sep;48(9):1161-7. doi: 10.1038/bmt.2013.51. Epub 2013 Apr 15. — View Citation

Reich-Slotky R, Colovai AI, Semidei-Pomales M, Patel N, Cairo M, Jhang J, Schwartz J. Determining post-thaw CD34+ cell dose of cryopreserved haematopoietic progenitor cells demonstrates high recovery and confirms their integrity. Vox Sang. 2008 May;94(4):351-7. doi: 10.1111/j.1423-0410.2007.001028.x. Epub 2008 Jan 2. — View Citation

Shevchenko JL, Kuznetsov AN, Ionova TI, Melnichenko VY, Fedorenko DA, Kartashov AV, Kurbatova KA, Gorodokin GI, Novik AA. Autologous hematopoietic stem cell transplantation with reduced-intensity conditioning in multiple sclerosis. Exp Hematol. 2012 Nov;40(11):892-8. doi: 10.1016/j.exphem.2012.07.003. Epub 2012 Jul 4. — View Citation

Snowden JA, Saccardi R, Allez M, Ardizzone S, Arnold R, Cervera R, Denton C, Hawkey C, Labopin M, Mancardi G, Martin R, Moore JJ, Passweg J, Peters C, Rabusin M, Rovira M, van Laar JM, Farge D; EBMT Autoimmune Disease Working Party (ADWP).; Paediatric Diseases Working Party (PDWP).. Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2012 Jun;47(6):770-90. doi: 10.1038/bmt.2011.185. Epub 2011 Oct 17. — View Citation

Steinman L. A molecular trio in relapse and remission in multiple sclerosis. Nat Rev Immunol. 2009 Jun;9(6):440-7. doi: 10.1038/nri2548. Review. — View Citation

von Büdingen HC, Kuo TC, Sirota M, van Belle CJ, Apeltsin L, Glanville J, Cree BA, Gourraud PA, Schwartzburg A, Huerta G, Telman D, Sundar PD, Casey T, Cox DR, Hauser SL. B cell exchange across the blood-brain barrier in multiple sclerosis. J Clin Invest. 2012 Dec;122(12):4533-43. doi: 10.1172/JCI63842. Epub 2012 Nov 19. — View Citation

Zozulya AL, Wiendl H. The role of regulatory T cells in multiple sclerosis. Nat Clin Pract Neurol. 2008 Jul;4(7):384-98. doi: 10.1038/ncpneuro0832. Epub 2008 Jun 24. Review. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Adverse Events	Type, occurence, severity, timing, seriousness and relatedness of adverse events and laboratory abnormalities	12 months
Secondary	Efficacy: EDSS Score	Measurement of disease progression by change in baseline of EDSS score	1 month post-infusion, 3 months month post-infusion, 6 months month post-infusion, 12 months month post-infusion
Secondary	Efficacy: RAND-36 Score	Measurement of Quality of Life by change in baseline of RAND-36 score	1 month post-infusion, 3 months month post-infusion, 6 months month post-infusion, 12 months month post-infusion