Safety and Efficacy of an Immunoablative Nonmyeloablative Conditioning Protocol for Autologous Bone Marrow Transplantation (BMT) in Patients With Multiple Sclerosis (MS)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of an immunoablative nonmyeloablative conditioning protocol for autologous bone marrow transplantation in patients with Multiple Sclerosis. Patients meeting inclusion and exclusion criteria will start an immunoablative nonmyeloablative conditioning regimen followed by autologous bone marrow transplantation. Patients will be followed for one year by a neurologist to evaluate the course of the disease after treatment.

Official Title
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Safety and Efficacy of an Immunoablative Nonmyeloablative Conditioning Protocol for Autologous Bone Marrow Transplantation in Patients With Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Procedure: Autologous bone marrow transplantation
* Drug: Fludarabine
* Drug: Cyclophosphamide
* Drug: Alemtuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consenting patients fulfilling the Poser's clinical criteria for definite MS Age: 18-65, males and females Relapsing and secondary progressive forms of MS with evidence of significant activity of MS (clinical and on the MRI). EDSS score of 2.0 to 7.0 (see table 1). Failure to at least one line of the currently available treatment, registered treatments (i.e. interferons, Copaxone, Tysabri, Gilenya, Tecfidera, immunosuppression) for MS. The lack of response to these treatments will be determined/defined by either an increase (deterioration) of one degree (or more) in the EDSS score, when baseline EDSS is less than 5.0 or 0.5 degree, when baseline EDSS is 5.0 or more, during the last year or the appearance of one major relapse of MS during the same period of time (under treatment), or evidence for new activity of MS (new T2 lesions or gadolinium enhancing lesions) during the last 12 months. Duration of disease: >2 years, except cases with rapid progression, i.e. annual relapse rate ≥2 per 2 years on a conventional treatment or malignant multiple sclerosis with very intense symptoms (types is in most cases deadly). Exclusion Criteria: Patients suffering from significant cardiac, renal or hepatic failure or any other disease that may risk the patient or interfere with the ability to undergo high dose immunosuppression associated toxicities (according to the existing limitations for autologous transplantation). Patients with active infections. Patients with severe cognitive decline or inability to understand and sign the informed consent. Patients who were treated with investigational protocols during the last 3 months prior to the inclusion. Patients who received high dose immunosuppression with autologous stem cell rescue in the past with no effect.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Fludarabine 30mg/m2 for 4 days, Cyclophosphamide 50mg/kg for 2 days, Alemtuzumab administered subcutaneously 24mg total dose. Autologous bone marrow transplantation | Procedure: Autologous bone marrow transplantation<br>* IMMUNOABLATIVE NONMYELOABLATIVE AUTOLOGOUS BONE MARROW TRANSPLANTATION on Day 0<br>Drug: Fludarabine<br>* 30mg/m2 on days -6 through -3<br>Drug: Cyclophosphamide<br>* 50mg/kg on days -5 through -4<br>Drug: Alemtuzumab<br>* 3mg on day -3, 9mg on day -2, 12 mg on day -1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Engraftment parameters of Neutrophils and Platelets | Absolute Neutrophil count >500 /microliter, Platelets>20,000/microliter | 1 year | 
| Transplant related mortality by Day 100 |  | Day 100 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the Expanded Disability Status Scale (EDSS score, as compared to baseline) |  | 1 year | 
| Overall survival (OS) at 1 year |  | 1 year | 
| Progression-free survival (PFS) at 1 year |  | 1 year | 
| Changes in MRI activity | T2 number | 1 year | 
| Changes in MRI activity | Volume of gadolinium enhancing lesions | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MS, BMT