High Dose Cyclophosphamide Followed by Glatiramer Acetate in the Treatment of Relapsing Remitting Multiple Sclerosis

• Status: Withdrawn
• Trial end date: 2010-11-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine if high-dose cyclophosphamide followed by a maintenance dose of glatiramer acetate is safe in patients with relapsing remitting multiple sclerosis (MS). The investigators hypothesize that institution of glatiramer acetate treatment following high-dose cyclophosphamide treatment will extend the period of disease free activity and further reduce the disability in patients with relapsing remitting multiple sclerosis. The investigators plan to investigate the properties of glatiramer acetate against the recurrence of MS disease activity following high dose cyclophosphamide induced cessation detectable autoimmunity. The investigators hypothesize that glatiramer acetate, given in the phase of immune reconstitution after high-dose cyclophosphamide, may bias the immune system to a more tolerated state, thus leading to more stable and potentially permanent remissions.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Johns Hopkins University; Sidney Kimmel Comprehensive Cancer Center
• Treatments: (T,G)-A-L; Cyclophosphamide; Glatiramer Acetate

Criteria

Inclusion criteria

1. Males and females between the ages of 18 and 70 years, inclusive.

2. Diagnosis of clinically definite MS according to the McDonald Criteria.

3. Must have been on conventional immunomodulatory treatment (interferon beta-1a, glatiramer acetate, or natalizumab) for at least 3 months OR have not tolerated conventional treatment OR have refused to start conventional treatment.

4. 2 or more total gadolinium enhancing lesions on each of two pretreatment MRI scans at screening and enrollment.

5. Subject must have EDSS ranging from 1.5 to 6.5.

6. Subject must have had at least one clinical exacerbation in the last year and this must have occurred after having been on Avonex, Betaseron, Copaxone, Rebif or Natalizumab therapy for at least 3 months. This does not apply if subject has refused to start conventional therapy.

7. Subject must have had a sustained (≥ 3 months) increase of > 1.0 on the EDSS (historical estimate allowed) between 3.0 and 5.5 or > 0.5 between 5.5 and 6.5 (while on therapy).

8. Written informed consent prior to any testing under this protocol, including screening tests and evaluations that are not considered part of the subject's routine care.

9. Women of childbearing potential should have a negative pregnancy test prior to entry into the study.

Exclusion criteria

1. Any risk of pregnancy--ALL female patients must have an effective means of birth control or be infertile due to hysterectomy, fallopian tube surgery, or premature menopause.

2. Cardiac ejection fraction of < 45%.

3. Serum creatinine > 2.0.

4. Patients who are pre-terminal or moribund.

5. Bilirubin > 2.0, transaminases > 2x normal.

6. Patients with EDSS < 3.0 or > 6.5.

7. Patients with pacemakers and implants who cannot get serial MRIs.

8. Patients with active infections until infection is resolved.

9. Patients with WBC count < 3000 cells/µl, platelets < 100,000 cells/µl and untransfused hemoglobin < 10 g/dl.