Phase II High-Dose Cyclophosphamide for Multiple Sclerosis

This study has been withdrawn prior to enrollment.
(I am changing locations to Johns Hopkins Medical Center)
Sponsor:
Information provided by:
Stony Brook University
ClinicalTrials.gov Identifier:
NCT00296205
First received: February 23, 2006
Last updated: July 21, 2009
Last verified: October 2006
  Purpose

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 Intervention Phase
Multiple Sclerosis
Drug: Cyclophosphamide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of High-dose Cyclophosphamide for Moderate to Severe Refractory Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by Stony Brook University:

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

Estimated Enrollment: 25
Study Start Date: October 2003
Estimated Study Completion Date: February 2006
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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00296205

Locations
United States, New York
Stony Brook University Hospital
Stony Brook, New York, United States, 11794-8174
Sponsors and Collaborators
Stony Brook University
Investigators
Principal Investigator: Douglas E Gladstone, MD Stony Brook University
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00296205     History of Changes
Other Study ID Numbers: 20055203
Study First Received: February 23, 2006
Last Updated: July 21, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Stony Brook University:
Multiple Sclerosis
Cyclophosphamide
autoimmune

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on April 17, 2014