Multiple SclerosisPhase 2NCT00296205
Phase II High-Dose Cyclophosphamide for Multiple Sclerosis
A Phase 2 study testing Cyclophosphamide in people with Multiple Sclerosis, run by Stony Brook University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Cyclophosphamide
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2003to Feb 2006
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
Show all 9Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Stony Brook University Hospital
Stony Brook, New York, 11794-8174
About this study
Official title: 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.
Read the 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.
- Conditions
- Multiple Sclerosis
- Being tested
- Cyclophosphamide
- Keywords
- Multiple Sclerosis, Cyclophosphamide, autoimmune
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
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 outcomes (1)
The secondary endpoint of this study is to evaluate time to EDSS score progression.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2006 (estimated)
- Study startOct 2003
- Study completionFeb 2006 (estimated)
Why it stopped: I am changing locations to Johns Hopkins Medical Center
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stony Brook University
- Sponsor type
- University, hospital or other
- Investigators
- Douglas E Gladstone, MD, Principal investigator, Stony Brook University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00296205
- Sponsor's protocol ID
- 20055203
- Status last verified
- Oct 2006
- First submitted
- 23 Feb 2006
- Last updated
- 22 Jul 2009
- Results posted
- No
Publications
Gladstone DE, Zamkoff KW, Krupp L, Peyster R, Sibony P, Christodoulou C, Locher E, Coyle PK. High-dose cyclophosphamide for moderate to severe refractory multiple sclerosis. Arch Neurol. 2006 Oct;63(10):1388-93. doi: 10.1001/archneur.63.10.noc60076. Epub 2006 Aug 14.
PubMed 16908728
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of High-dose Cyclophosphamide for Moderate to Severe Refractory Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT00296205
- Acronym / sponsor ID
- 20055203
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple Sclerosis, Cyclophosphamide, autoimmune
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: I am changing locations to Johns Hopkins Medical Center
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Stony Brook UniversityUniversity, hospital or other
- Study start
- Oct 2003
- Study completion
- Feb 2006 (estimated)
- First posted
- 24 Feb 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cyclophosphamide | Drug | – |
Primary outcome
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.
1 secondary outcome
The secondary endpoint of this study is to evaluate time to EDSS score progression.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2009.
- Results publication: PubMed 16908728Gladstone DE, Zamkoff KW, Krupp L, Peyster R, Sibony P, Christodoulou C, Locher E, Coyle PK. High-dose cyclophosphamide for moderate to severe refractory multiple sclerosis. Arch Neurol. 2006 Oct;63(10):1388-93. doi: 10.1001/archneur.63.10.noc60076. Epub 2006 Aug 14.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Douglas E Gladstone, MD principal investigator
Stony Brook University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cyclophosphamide in people with Multiple Sclerosis, run by Stony Brook University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 22 Jul 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary 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.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00296205, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2009.