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Stem Cell Therapy for Patients With Multiple Sclerosis Failing Alternate Approved Therapy- A Randomized Study

Information source: Northwestern University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Multiple Sclerosis

Intervention: Hematopoietic Stem Cell Therapy (Procedure); Standard treatment with a conventional drug (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Northwestern University

Official(s) and/or principal investigator(s):
Richard Burt, MD, Principal Investigator, Affiliation: Northwestern University

Overall contact:
Dzemila Spahovic, MD, Phone: 312-695-4960, Email: d-spahovic@northwestern.edu

Summary

Multiple sclerosis (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 or 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, glatiramer acetate, mitoxantrone, natalizumab, fingolimod, or tecfidera) in patients with inflammatory (relapsing) MS despite treatment with alternate approved therapy.

Clinical Details

Official title: Hematopoietic Stem Cell Therapy for Patients With Inflammatory Multiple Sclerosis Failing Alternate Approved Therapy: A Randomized Study

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: EDSS

Detailed description: To assess the efficacy of autologous PBSCT versus FDA approved standard of care ( i. e. interferon, glatiramer acetate, mitoxantrone, natalizumab, fingolimod, or tecfidera) for inflammatory multiple sclerosis (MS) failing failing alternate approved therapy. The endpoints to be considered in this study are: 2. 1 Primary Endpoint: Disease progression, defined as a 1 point increase in the Expanded Disability Status Scale (EDSS) on consecutive evaluations at least 6 months apart and not due to a non-MS disease process. Patients will be followed for 5 years after randomization. 2. 2 Secondary Endpoints: 1. Number of relapses, defined as acute neurologic deterioration occurring after engraftment and lasting more than 24 hours, accompanied by objective worsening on neurological examination that are documented by a blinded neurologist and not explained by fever, infection, stress or heat related pseudo-exacerbation. Supportive confirmation by enhancement on MRI is preferred but not mandatory. 2. Ambulation index 3. Twenty-five foot timed walk 4. Nine hole PEG test

5. PASAT- 3 second and PASAT - 2 second

6. MSFC 7. MRI enhancing lesions and T1 and T2 burden of disease per MRI-AC MRI protocol 8. SF-36 9. Scripps NRS 10. Survival

Eligibility

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. 1. Age between18-55, inclusive. 2. Diagnosis of MS using revised McDonald criteria of clinically definite MS (Appendix I). 3. An EDSS score of 2. 0 to 6. 0 (Appendix II). 4. Inflammatory disease despite treatment with standard disease modifying therapy including at least 6 months of interferon or copaxone. Inflammatory disease is defined based on both MRI (gadolinium enhancing lesions) and clinical activity (acute relapses *treated with IV or oral high dose corticosteroids and prescribed by a neurologist). Minimum disease activity required for failure is defined as: a) two or more *steroid treated clinical relapses with documented new objective signs on neurological examination documented by a neurologist within the year prior to the study, or b) one *steroid treated clinical relapse within the year prior to study and evidence on MRI of active inflammation (i. e., gadolinium enhancement) within the last 12 months on an occasion separate from the clinical relapse (3 months before or after the clinical relapse).

- A steroid treated relapse will include a relapse that was severe enough to

justify treatment but due to patient intolerance of steroids, or a history of non-response to steroids, they were offered but not used. 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 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. 3. Positive pregnancy test 4. Inability or unwillingness to pursue effective means of birth control from the time of evaluation for eligibility until 6 months posttransplant (if on transplant) or until appropriate for non-transplant treatment (if on control arm). Effective birth control is defined as 1) abstinence defined as refraining from all acts of vaginal intercourse; 2) consistent use of birth control pills; 3) injectable birth control methods (Depo-provera, Norplant); 4) tubal sterilization or male partner who has undergone vasectomy; 5) placement of an intrauterine device (IUD); or 6) use, with every act of intercourse, of diaphragm with contraceptive jelly and/or condoms with contraceptive foam. 5. Failure to willingly accept or comprehend irreversible sterility as a side effect of therapy 6. FEV1/FVC < 60% of predicted after bronchodilator therapy (if necessary) 7. DLCO < 50% of predicted (for the transplant arm) 8. Resting LVEF < 50 % 9. Bilirubin > 2. 0 mg/dl 10. Serum creatinine > 2. 0 mg/dl 11. Known hypersensitivity to mouse, rabbit, or E. Coli derived proteins, or to iron compounds/medications 12. Presence of metallic objects implanted in the body that would preclude the ability of the patient to safely have MRI exams 13. Diagnosis of primary progressive MS 14. Diagnosis of secondary 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 bacteriuria 18. Use of natalizumab (Tysabri) within the previous 6 months 19. Use of fingolimod (Gilenya) within the previous 3 months 20. Use of Teriflunomide (Aubagio) within the previous 2 years unless cleared from the body (plasma concentration < 0. 02mcg/ml) following elimination from the body with cholestyramine 8g three times a day for 11 days 21. Prior treatment with CAMPATH (alemtuzumab) 22. Prior treatment with mitoxantrone 23. Any hereditary neurological disease such as Charcot-Marie-Tooth disease (CMT) or Spinocerebellar ataxia (SCA) are contraindications 24. Use of tecfidera within the previous 3 months

- For patients who clearly have inflamatory disease, an exception can be made if

agreed upon by study PI and at least two study neurologists.

Locations and Contacts

Dzemila Spahovic, MD, Phone: 312-695-4960, Email: d-spahovic@northwestern.edu

Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, United States; Recruiting
Dzemila Spahovic, MD, Phone: 312-695-4960, Email: d-spahovic@northwestern.edu
Richard Burt, MD, Principal Investigator
Additional Information

Starting date: January 2006
Last updated: March 23, 2015

Page last updated: August 23, 2015

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