Location: Northwest University , Chicago, Il.

MS is at onset an immune-mediated demyelinating disease. In most cases, it starts as a relapsing-remitting disease with distinct attacks and no symptoms between flares. Over years or decades, virtually all cases transition into a progressive disease in which insidious and slow neurologic deterioration occurs with or without acute flares. Relapsing-remitting disease is often responsive to immune suppressive modulating therapies, while immune based therapies are generally ineffective in patients with a progressive clinical course. This clinical course and response to immune suppression, as well as neuropathology and neuroimaging studies, suggest that disease progression is associated with axonal atrophy. Disability correlates better with measures of axonal atrophy than immune mediated demyelination. Therefore, immune based therapies, in order to be effective, need to be started early in the disease course while MS is predominately an immune-mediated and inflammatory disease. While current immune-based therapies delay disability, no intervention has been proven to prevent progressive disability. We propose, as a randomized study, autologous unmanipulated PBSCT using a conditioning regimen of cyclophosphamide and rATG versus FDA approved standard of care (i.e., interferon, copaxone, or mitoxantrone) in patients with inflammatory (relapsing) MS despite treatment with interferon.

Eligibility:
Inclusion Criteria:
1. Age between 18–55, inclusive
2. Diagnosis of MS using Poser criteria of “clinically definite” MS
3. An EDSS of 2.0 to 6.0
4. Inflammatory disease despite primary disease modifying therapy with at
least 4 months of interferon. Inflammatory disease is defined by either MRI
showing adolinium enhancing lesions or clinically as acute relapses treated
with IV solumedrol. Failure is defined as two or more clinical relapses with
documented neurological changes within one year prior to the study. (Note:
Relapses must have required treatment with corticosteroids). Failure may
also be defined as one relapse within the year prior to the study if there is
evidence on MRI of active inflammation (i.e., gadolinium enhancement).

Exclusion Criteria:
1. Any illness that, in the opinion of the investigators, would jeopardize the
ability of the patient to tolerate aggressive chemotherapy.
2. Prior therapy with mitoxantrone.
3. Prior history of malignancy except localized basal cell, squamous skin
cancer or carcinoma in situ of the cervix. Other malignancies for which the
patient is judged to be cured, such as head and neck cancer, or breast
cancer will be considered on an individual basis.
4. Positive pregnancy test.
5. Inability or unwillingness to pursue effective means of birth control.
Effective birth control is defined as 1) refraining from all acts of vaginal
intercourse (abstinence); 2) consistent use of birth control pills; 3)
injectable birth control methods (Depo-Provera, Norplant); 4) tubal
sterilization or male who has undergone a vasectomy; 5) placement of an
IUD (intrauterine devise); or 6) use, with every act of intercourse, of
diaphragm with contraceptive jelly and/or condoms with contraceptive
foam.
6. Failure to willingly accept or comprehend irreversible sterility as a side
effect of therapy.
7. FEV1/FVC < 60% of predicted after bronchodilator therapy (if necessary).
8. DLCO < 50% of predicted.
9. Resting LVEF < 50%.
10. Bilirubin> 2.0mg/dl.
11. Serum Creatinine> 2.0 mg/dl
12. Known hypersensitivity to mouse, rabbit, or E. Coli derived proteins, or to
iron compounds/medications.
13. Presence of metallic objects implanted in the body that would preclude
the ability of the patient to safely have MRI exams.
14. Diagnosis of primary progressive MS.
15. Platelet count < 100,000/ul, WBC < 1,500 cells/mm3.
16. Psychiatric illness, mental deficiency or cognitive dysfunction making
compliance with treatment or informed consent impossible.
17. Active infection except asymptomatic bacteruria.

Procedure/Benefit: To compare the clinical outcomes for patients treated with standard therapy (including interferons, steroids, IVIG and chemotherapy), vs. those who undergo stem cell transplantation.

Information: Kathleen Quigley, RN, BSN, MBA, phone: 312-908-0059

This entry was posted on Monday, May 18th, 2009 at 8:33 am and is filed under All Articles, Clinical Trials. You can follow any responses to this entry through the RSS 2.0 feed.