High Dose Chemo With Stem Cell Transplant as Treatment for Multiple Sclerosis That Failed Prior Treatment

NCT01679041 | Terminated Phase 2 DMC

• 1 other identifier: 20112015
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate the toxicity and the effectiveness of high dose chemotherapy with HPC transplant Multiple Sclerosis that has failed at least two lines of therapy

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• To evaluate the toxicity of autologous HPC transplant in patients with multiple sclerosis that have failed at least two lines of disease modifier therapy

  All follow-up appointments will be carried out at Texas Oncology-Amarillo Cancer Center. Patients will be monitored for clinical toxicities and using laboratory blood tests for renal functions, hepatic functions, and bone marrow functions at At discharge post-transplant, then again at 6 weeks, 3 months, 6 months, 9 months, 12 months and after that 6 monthly until death..

  At 5 years post transplant

Secondary Outcomes (1)

• To evaluate the effectiveness of high dose chemotherapy with HPC transplant for multiple sclerosis sclerosis that has failed at least two lines of therapy

  Assessed at baseline, tat 3 months, 6 months, 9 months, 12 months, and then after every 12 months until death

Study Arms (1)

Single Arm

EXPERIMENTAL

Conditioning regimens with Alemtuzumab, Fludarabine, and Cyclophosphamide will be used for all patients.

Drug: Alemtuzumab; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

Alemtuzumab DRUG

Alemtuzumab 10 mg given IV on day 1 of the 5 day conditional regimen

Single Arm

Fludarabine DRUG

Fludarabine 25mg/m2 daily given IV on days 1-5 of the 5 day conditioning regimen

Single Arm

Cyclophosphamide DRUG

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

Single Arm

Eligibility Criteria

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

You may qualify if:

• Age between 18-60, inclusive
• 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.

You may not qualify if:

• Diagnosis of primary progressive MS.

Sponsors & Collaborators

• Seah Lim M.D.: lead

Study Sites (3)

Amarillo Diagnostic Clinic

Amarillo, Texas, 79106, United States

Location

Dr Ruby Saulog

Amarillo, Texas, 79106, United States

Location

Texas Oncology

Amarillo, Texas, 79106, United States

Location

Related Publications (12)

• 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.

  PMID: 19186105 BACKGROUND

• 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.

  PMID: 17133541 BACKGROUND

• 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.

  PMID: 18805841 BACKGROUND

• 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.

  PMID: 17942513 BACKGROUND

• 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.

  PMID: 9040585 BACKGROUND

• 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.

  PMID: 15957523 BACKGROUND

• 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.

  PMID: 20304084 BACKGROUND

• 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.

  PMID: 17961728 BACKGROUND

• 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.

  PMID: 21387374 BACKGROUND

• 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.

  PMID: 18832930 BACKGROUND

• 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.

  PMID: 17263012 BACKGROUND

• 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.

  PMID: 19465851 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Alemtuzumab; fludarabine; Cyclophosphamide

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Seah Lim, MD

  Texas Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Principal Investigator (MD)

Study Record Dates

• First Submitted: August 29, 2012
• First Posted: September 5, 2012
• Study Start: November 1, 2012
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: November 25, 2013

Record last verified: 2013-11

Locations

US (3)