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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01679041
Recruitment Status : Terminated (Insufficient accruals; PI leaving site)
First Posted : September 5, 2012
Last Update Posted : November 25, 2013
Information provided by (Responsible Party):
Seah Lim M.D., Texas Oncology Cancer Center

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

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Drug: Alemtuzumab Drug: Fludarabine Drug: Cyclophosphamide Phase 2

Detailed Description:

Multiple sclerosis is an inflammatory autoimmune disease characterized by loss of myelin and axonal damage, having typical contrast-enhanced MRI foci as an imaging counterpart. MS shows three main patterns of clinical course: relapsing/remitting, primary progressive and secondary progressive.Concerning disease pattern, secondary progressive is the standard indication, to avoid overtreatment in relapsing/remitting patients or ineffectual treatment in primary relapsing patients.

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of High Dose Chemotherapy With Autologous Hematopoietic Progenitor Cell Transplant for Multiple Sclerosis That Failed at Least Two Lines of Therapy
Study Start Date : November 2012
Actual Primary Completion Date : November 2013
Actual Study Completion Date : November 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Single Arm
Conditioning regimens with Alemtuzumab, Fludarabine, and Cyclophosphamide will be used for all patients.
Drug: Alemtuzumab
Alemtuzumab 10 mg given IV on day 1 of the 5 day conditional regimen

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

Drug: 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

Primary Outcome Measures :
  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 [ Time Frame: At 5 years post transplant ]
    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..

Secondary Outcome Measures :
  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 [ Time Frame: Assessed at baseline, tat 3 months, 6 months, 9 months, 12 months, and then after every 12 months until death ]
    hen rechecked Neurologic evaluations will be carried out in the offices of the two neurology co-Investigators and the information provided to the transplant physicians for record. Patient will also undergo a repeat MRI scan at 3 months, 6 months, 9 months, 12 months, and then after every 12 months until death, after the transplant to evaluate changes in the number of MS plaques. Subsequent MRI scan will be determined by the patient's neurologist as is needed clinically.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

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.

Exclusion Criteria:

Diagnosis of primary progressive MS.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01679041

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United States, Texas
Amarillo Diagnostic Clinic
Amarillo, Texas, United States, 79106
Dr Ruby Saulog
Amarillo, Texas, United States, 79106
Texas Oncology
Amarillo, Texas, United States, 79106
Sponsors and Collaborators
Seah Lim M.D.
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Principal Investigator: Seah Lim, MD Texas Oncology

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Responsible Party: Seah Lim M.D., Sponsor-Principal Investigator (MD), Texas Oncology Cancer Center Identifier: NCT01679041    
Other Study ID Numbers: 20112015
First Posted: September 5, 2012    Key Record Dates
Last Update Posted: November 25, 2013
Last Verified: November 2013
Additional relevant MeSH terms:
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Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological