Phase II High-Dose Cyclophosphamide for Multiple Sclerosis

July 21, 2009 updated by: Stony Brook University

Phase II Trial of High-dose Cyclophosphamide for Moderate to Severe Refractory Multiple Sclerosis

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

25

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Stony Brook, New York, United States, 11794-8174
        • Stony Brook University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Outcome Measure
The secondary endpoint of this study is to evaluate time to EDSS score progression.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stony Brook University

Investigators

  • Principal Investigator: Douglas E Gladstone, MD, Stony Brook University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2003

Study Completion (Anticipated)

February 1, 2006

Study Registration Dates

First Submitted

February 23, 2006

First Submitted That Met QC Criteria

February 23, 2006

First Posted (Estimate)

February 24, 2006

Study Record Updates

Last Update Posted (Estimate)

July 22, 2009

Last Update Submitted That Met QC Criteria

July 21, 2009

Last Verified

October 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20055203

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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