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

NCT03113162 | Unknown Phase 1

• 1 other identifier: MMCIRB 2015-024
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Sclerosis

Keywords

multiple sclerosis; HSCT

Outcome Measures

Primary Outcomes (1)

• Safety: Adverse Events

  Type, occurence, severity, timing, seriousness and relatedness of adverse events and laboratory abnormalities

  12 months

Secondary Outcomes (2)

• Efficacy: EDSS Score

  1 month post-infusion, 3 months month post-infusion, 6 months month post-infusion, 12 months month post-infusion

• Efficacy: RAND-36 Score

  1 month post-infusion, 3 months month post-infusion, 6 months month post-infusion, 12 months month post-infusion

Study Arms (1)

Autologous Hematopoietic Stem Cell with BEAM Regimen

EXPERIMENTAL

Autologous HSCT following Reduced-Intensity BEAM Regimen

Biological: Autologous Hematopoietic Stem Cell; Drug: BEAM Regimen

Interventions

Autologous Hematopoietic Stem Cell BIOLOGICAL

Autologous Hematopoietic Stem Cell with BEAM Regimen

BEAM Regimen DRUG

Reduced-intensity BEAM for Immunoablation

Also known as: BCNU, Etoposide, Cytarabine, Melphalan

Autologous Hematopoietic Stem Cell with BEAM Regimen

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Makati Medical Center: lead

Study Sites (1)

Makati Medical Center

Makati, 1229, Philippines

RECRUITING

Related Publications (21)

• Akkok CA, Liseth K, Hervig T, Ryningen A, Bruserud O, 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.

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• 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. No abstract available.

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• 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.

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• Cabezudo E, Dalmases C, Ruz M, Sanchez JA, Torrico C, Sola C, Querol S, Garcia J. Leukapheresis components may be cryopreserved at high cell concentrations without additional loss of HPC function. Transfusion. 2000 Oct;40(10):1223-7. doi: 10.1046/j.1537-2995.2000.40101223.x.

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• 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.

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• De Boer F, Drager 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. doi: 10.1038/sj.bmt.1701495.

  PMID: 9877274 BACKGROUND

• Farge D, Labopin M, Tyndall A, Fassas A, Mancardi GL, Van Laar J, Ouyang J, Kozak T, Moore J, Kotter 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.

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• 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. doi: 10.1038/sj.bmt.1700944.

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• 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. doi: 10.1016/j.jns.2004.04.020.

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• 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.

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• 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. doi: 10.1111/j.1537-2995.2007.01447.x. Epub 2007 Aug 21.

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• 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, Curro 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.

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• Passweg JR, Baldomero H, Bregni M, Cesaro S, Dreger P, Duarte RF, Falkenburg JH, Kroger 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.

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• 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.

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• 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.

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MeSH Terms

Conditions

Multiple Sclerosis

Interventions

BEAM regimen; Carmustine; Etoposide; Cytarabine; Melphalan

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Darwin Albert A Dasig, MD

  Makati Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marviel T Berboso, RN

CONTACT

8888999; Inquiry.CTC@makatimed.net.ph

Jose Maria C Avila, MD

CONTACT

8888999; stemcell@makatimed.net.ph

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 10, 2017
• First Posted: April 13, 2017
• Study Start: May 29, 2015
• Primary Completion: May 29, 2020
• Study Completion: May 29, 2022
• Last Updated: May 5, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

PH (1)