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Phase II High-Dose Cyclophosphamide for Multiple Sclerosis

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: NCT00296205
Recruitment Status : Withdrawn (I am changing locations to Johns Hopkins Medical Center)
First Posted : February 24, 2006
Last Update Posted : July 22, 2009
Information provided by:
Stony Brook University

Brief Summary:
The purpose of this study is to determine what percentage of patients receiving high-dose Cyclophosphamide may experience a halt in the worsening of their disease or experience improvement of their disease and for how long the benefit may last.

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

Detailed Description:

Multiple sclerosis (MS) is the major disabling neurologic disease of young adults,and represents the most common immune-mediated inflammatory and demyelinating disorder of the central nervous system (CNS). Active inflammatory lesions contain components that include T cells, macrophages, and activated microglia. Within these lesions myelin is removed, axons are damaged and oligodendrocytes may be lost. In lesions undergoing inflammatory demyelination axonal injury also occurs. The disability MS produces is underscored by the nearly fifty percent of patients who will require ambulatory aids within 15 years after disease onset.

Currently, there is no cure for MS. Therapy is targeted at changing the short-term natural history of MS: to decrease attack rates and to postpone long-term disability. At present, interferon beta and glatiramer acetate form the foundation of therapy for relapsing MS. Mitoxantrone is approved for more severe cases of relapsing MS, such as those with rapidly accumulating neurologic impairments.

High-dose cyclophosphamide (HDC) is a non-bone marrow transplant treatment option for those afflicted by severe, refractory immune-mediated illnesses by pathologic autoreactive lymphocytes. The goal of this therapy is to induce immunoablation without myeloablation: that is, to eradicate offending B and T cells responsible for the illness while sparing the pluripotent blood stem cell of any ill effect. Since 1966, multiple publications on numerous immune-mediated illnesses have shown HDC without stem-cell rescue to decrease disease activity and improve quality of life

In this protocol we study HDC for severe, refractory MS. The primary goal is to assess the safety of HDC in this population, where no data exists regarding the tolerability of high-dose chemotherapy without stem-cell rescue. The treatment goal is not to induce disease regression (resolution of fixed neurologic deficits), but rather to stop disease progression without further remittive therapy.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of High-dose Cyclophosphamide for Moderate to Severe Refractory Multiple Sclerosis
Study Start Date : October 2003
Estimated Study Completion Date : February 2006

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. The primary endpoint of this study is to evaluate the response rate of MS patients after high-dose cyclophosphamide therapy as determined by a sustained (greater than 6 months) decrease of greater than or equal to 1.0 in their EDSS score.

Secondary Outcome Measures :
  1. The secondary endpoint of this study is to evaluate time to EDSS score progression.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of secondary progressive (SPMS), primary progressive (PPMS) or progressive relapsing (PRMS) multiple sclerosis
  • A diagnosis of MS will be established by fulfilling criteria "Recommended Diagnostic Criteria for Multiple Sclerosis: Guidelines from the Internal Panel on the Diagnosis of Multiple Sclerosis"
  • The subtype of MS will be established by the natural history of the disease
  • Age >18 but < 75 years
  • An extended disability status scale (EDSS) score of >3.5 after two standard treatment regimens IFNB1a IFNB1b Glatiramer acetate Mitoxanthrone Steroids, plasmapheresis or IVIG individually or in combination constitute a single treatment regimen
  • Patient must have a left ventricular ejection fraction of > 45%
  • Serum Creatinine <3mg/dL
  • For women of childbearing potential, serum βHCG (less than seven days before start of cyclophosphamide)
  • Willingness to participate in a clinical trial

Exclusion Criteria:

  • Patients who are preterminal or moribund
  • Patients with active malignancies
  • Patients with chromosomal abnormalities or peripheral blood counts suggestive of myelodysplastic syndrome
  • Patients with active bacterial or fungal infections requiring oral or intravenous antimicrobials are not eligible until resolution of the infection
  • Pregnant women and breast-feeding women
  • Patients with known intolerance to G-CSF

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): NCT00296205

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United States, New York
Stony Brook University Hospital
Stony Brook, New York, United States, 11794-8174
Sponsors and Collaborators
Stony Brook University
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Principal Investigator: Douglas E Gladstone, MD Stony Brook University
Publications of Results:
Layout table for additonal information Identifier: NCT00296205    
Other Study ID Numbers: 20055203
First Posted: February 24, 2006    Key Record Dates
Last Update Posted: July 22, 2009
Last Verified: October 2006
Keywords provided by Stony Brook University:
Multiple Sclerosis
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