High Dose Chemo With Stem Cell Transplant as Treatment for Multiple Sclerosis That Failed Prior Treatment
NCT ID: NCT01679041
Last Updated: 2013-11-25
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
TERMINATED
PHASE2
1 participants
INTERVENTIONAL
2012-11-30
2013-11-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Currently, MS is the most common autoimmune disease that have been treated with autologous HPC transplants (Fagius et al, 2009; Burt et al, 2009; Saccardi et al, 2006). More than 350 consecutive cases have been reported by the EBMT over the last decade. Most patients who underwent autologous HPC transplant for MS in the early studies had secondary progressive MS, and relatively fewer had relapsing remitting disease, with a Kurtzke Expanded Disability Status Scale (EDSS) of 3.0-9.5 at the time of transplant. Significant objective and subjective improvements have been reported in up to 70% of these patients.
The following conditioning regimens will be used, with Alemtuzumab, Fludarabine, and Cyclophosphamide will be used for all patients. Prophylaxis of Acyclovir, Levaquin, and Fluconazole will be given to prevent infections. The autologous HPC will be infused within 48-72 hours of completing the chemotherapy. The patients will receive additional supportive care medications and treatments as necessary. Neutrophil engraftment will be defined as the day on which the ANC rises to \> 500 cells/ml for two consecutive days. Platelet engraftment will be defined as the first day on which the platelet count rises to \> 20,000/ml over a 7-day interval without transfusion support.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Single Arm
Conditioning regimens with Alemtuzumab, Fludarabine, and Cyclophosphamide will be used for all patients.
Alemtuzumab
Alemtuzumab 10 mg given IV on day 1 of the 5 day conditional regimen
Fludarabine
Fludarabine 25mg/m2 daily given IV on days 1-5 of the 5 day conditioning regimen
Cyclophosphamide
Cyclophosphamide is given 3 gm/m2 for mobilization, and then repeated during 5 day conditioning regimen w/ doses of 50mg/kg/day on days 1-4
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Alemtuzumab
Alemtuzumab 10 mg given IV on day 1 of the 5 day conditional regimen
Fludarabine
Fludarabine 25mg/m2 daily given IV on days 1-5 of the 5 day conditioning regimen
Cyclophosphamide
Cyclophosphamide is given 3 gm/m2 for mobilization, and then repeated during 5 day conditioning regimen w/ doses of 50mg/kg/day on days 1-4
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
Patients carry a diagnosis of multiple sclerosis, according to the McDonald's criteria for diagnosis (Polman et al, 2011).
Must have a neurologist providing the primary care for the MS and be willing to be evaluated for the multiple sclerosis by the two neurologists who are the co-investigators in the protocol.
Must be documented to be HIV negative.
An EDSS of 3.5 - 5.5
Patients must be able to give written consent.
Inflammatory disease despite primary disease modifying therapy with at least 6 months of interferon and another disease modifying therapy, including fingolimod,glativamir, natalizumab, and mitoxantrone. Failure is defined as two or more clinical relapses with documented neurologic changes (excluding sensory changes) within the year prior to the study. (NOTE: Relapses must have required treatment with corticosteroids). Failure may also be defined as one relapse (excluding sensory changes) treated with methylprednisone and, on a separate occasion within the previous 12 months, evidence of active inflammation (i.e. gadolinium enhancement on MRI scan of the CNS).
No previous history of allergic reaction to cyclophosphamide, G-CSF or mesna
Patients must not be pregnant
Failure to accept or comprehend irreversible sterility as a potential side effect of therapy.
Life expectancy of more than 6 months
No evidence of myelodysplastic syndrome on peripheral blood smear
Not allergic to cyclophosphamide, mesna, fludarabine or alemtuzumab
Baseline serum creatinine must be \<1.5 mg/dL, left ventricular ejection fraction \>55%, adequate pulmonary functions (oxygen saturation at room air of \>90%), and AST and ALT not \> 2x upper limits of normal, and no history of previous or active malignancy, except for localized cutaneous basal or squamous cell carcinoma in situ of the cervix.
Exclusion Criteria
18 Years
60 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Seah Lim M.D.
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Seah Lim M.D.
Sponsor-Principal Investigator (MD)
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Seah Lim, MD
Role: PRINCIPAL_INVESTIGATOR
Texas Oncology
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Amarillo Diagnostic Clinic
Amarillo, Texas, United States
Dr Ruby Saulog
Amarillo, Texas, United States
Texas Oncology
Amarillo, Texas, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
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.
Burt RK, Marmont A, Oyama Y, Slavin S, Arnold R, Hiepe F, Fassas A, Snowden J, Schuening F, Myint H, Patel DD, Collier D, Heslop H, Krance R, Statkute L, Verda L, Traynor A, Kozak T, Hintzen RQ, Rose JW, Voltarelli J, Loh Y, Territo M, Cohen BA, Craig RM, Varga J, Barr WG. Randomized controlled trials of autologous hematopoietic stem cell transplantation for autoimmune diseases: the evolution from myeloablative to lymphoablative transplant regimens. Arthritis Rheum. 2006 Dec;54(12):3750-60. doi: 10.1002/art.22256. No abstract available.
Fagius J, Lundgren J, Oberg G. Early highly aggressive MS successfully treated by hematopoietic stem cell transplantation. Mult Scler. 2009 Feb;15(2):229-37. doi: 10.1177/1352458508096875. Epub 2008 Sep 19.
Kimiskidis V, Sakellari I, Tsimourtou V, Kapina V, Papagiannopoulos S, Kazis D, Vlaikidis N, Anagnostopoulos A, Fassas A. Autologous stem-cell transplantation in malignant multiple sclerosis: a case with a favorable long-term outcome. Mult Scler. 2008 Mar;14(2):278-83. doi: 10.1177/1352458507082604. Epub 2007 Oct 17.
Lim SH, Kell J, al-Sabah A, Bashi W, Bailey-Wood R. Peripheral blood stem-cell transplantation for refractory autoimmune thrombocytopenic purpura. Lancet. 1997 Feb 15;349(9050):475. doi: 10.1016/S0140-6736(05)61187-7. No abstract available.
Mancardi GL, Murialdo A, Rossi P, Gualandi F, Martino G, Marmont A, Ciceri F, Schenone A, Parodi RC, Capello E, Comi G, Uccelli A. Autologous stem cell transplantation as rescue therapy in malignant forms of multiple sclerosis. Mult Scler. 2005 Jun;11(3):367-71. doi: 10.1191/1352458505ms1181cr.
Pasquini MC, Griffith LM, Arnold DL, Atkins HL, Bowen JD, Chen JT, Freedman MS, Kraft GH, Mancardi GL, Martin R, Muraro PA, Nash RA, Racke MK, Storek J, Saccardi R. Hematopoietic stem cell transplantation for multiple sclerosis: collaboration of the CIBMTR and EBMT to facilitate international clinical studies. Biol Blood Marrow Transplant. 2010 Aug;16(8):1076-83. doi: 10.1016/j.bbmt.2010.03.012. Epub 2010 Mar 18.
Passweg J, Tyndall A. Autologous stem cell transplantation in autoimmune diseases. Semin Hematol. 2007 Oct;44(4):278-85. doi: 10.1053/j.seminhematol.2007.08.001.
Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011 Feb;69(2):292-302. doi: 10.1002/ana.22366.
Saccardi R, Di Gioia M, Bosi A. Haematopoietic stem cell transplantation for autoimmune disorders. Curr Opin Hematol. 2008 Nov;15(6):594-600. doi: 10.1097/MOH.0b013e3283136700.
Saccardi R, Kozak T, Bocelli-Tyndall C, Fassas A, Kazis A, Havrdova E, Carreras E, Saiz A, Lowenberg B, te Boekhorst PA, Gualandio F, Openshaw H, Longo G, Pagliai F, Massacesi L, Deconink E, Ouyang J, Nagore FJ, Besalduch J, Lisukov IA, Bonini A, Merelli E, Slavino S, Gratwohl A, Passweg J, Tyndall A, Steck AJ, Andolina M, Capobianco M, Martin JL, Lugaresi A, Meucci G, Saez RA, Clark RE, Fernandez MN, Fouillard L, Herstenstein B, Koza V, Cocco E, Baurmann H, Mancardi GL; Autoimmune Diseases Working Party of EBMT. Autologous stem cell transplantation for progressive multiple sclerosis: update of the European Group for Blood and Marrow Transplantation autoimmune diseases working party database. Mult Scler. 2006 Dec;12(6):814-23. doi: 10.1177/1352458506071301.
Tyndall A, Gratwohl A. Adult stem cell transplantation in autoimmune disease. Curr Opin Hematol. 2009 Jul;16(4):285-91. doi: 10.1097/MOH.0b013e32832aacb3.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
20112015
Identifier Type: -
Identifier Source: org_study_id