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

NCT00939549 | Withdrawn Phase 2 DMC

• 1 other identifier: NA_00016884
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Relapsing Remitting Multiple Sclerosis

Keywords

High dose cyclophosphamide

Outcome Measures

Primary Outcomes (1)

• Safety - Serious adverse events

  2 years

Secondary Outcomes (3)

• Radiologic - reduction in the number of gadolinium enhancing lesions, T2 plaque burden, and change in brain parenchymal fraction.

  2 years

• Clinical/Neurological - Change in disability

  2 years

• Immunological - change in immune profile

  2 years

Study Arms (1)

High-dose cyclohosphamide

EXPERIMENTAL

Drug: Cyclophosphamide/Glatiramer acetate

Interventions

Cyclophosphamide/Glatiramer acetate DRUG

Cyclophosphamide 50 mg/kg IV each day for four consecutive days. Glatiramer acetate 20 mg SC daily for 1 year.

High-dose cyclohosphamide

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females between the ages of 18 and 70 years, inclusive.
• Diagnosis of clinically definite MS according to the McDonald Criteria.
• 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.
• or more total gadolinium enhancing lesions on each of two pretreatment MRI scans at screening and enrollment.
• Subject must have EDSS ranging from 1.5 to 6.5.
• 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.
• 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).
• 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.
• Women of childbearing potential should have a negative pregnancy test prior to entry into the study.

You may not qualify if:

• 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.
• Cardiac ejection fraction of \< 45%.
• Serum creatinine \> 2.0.
• Patients who are pre-terminal or moribund.
• Bilirubin \> 2.0, transaminases \> 2x normal.
• Patients with EDSS \< 3.0 or \> 6.5.
• Patients with pacemakers and implants who cannot get serial MRIs.
• Patients with active infections until infection is resolved.
• Patients with WBC count \< 3000 cells/µl, platelets \< 100,000 cells/µl and untransfused hemoglobin \< 10 g/dl.

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins Hospital Multiple Sclerosis Center

Baltimore, Maryland, 21287, United States

Location

Related Publications (1)

• Krishnan C, Kaplin AI, Brodsky RA, Drachman DB, Jones RJ, Pham DL, Richert ND, Pardo CA, Yousem DM, Hammond E, Quigg M, Trecker C, McArthur JC, Nath A, Greenberg BM, Calabresi PA, Kerr DA. Reduction of disease activity and disability with high-dose cyclophosphamide in patients with aggressive multiple sclerosis. Arch Neurol. 2008 Aug;65(8):1044-51. doi: 10.1001/archneurol.65.8.noc80042. Epub 2008 Jun 9.

  PMID: 18541787 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Cyclophosphamide; Glatiramer Acetate

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Justin McArthur, MBBS, MPH

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Robert Brodsky, M.D

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Daniel Harrison, MD

  Johns Hopkins University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2009
• First Posted: July 15, 2009
• Study Start: November 1, 2010
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: September 26, 2018

Record last verified: 2018-09

Locations

US (1)