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

Not Applicable

• Conditions: Multiple Sclerosis
• Interventions: Procedure: Autologous bone marrow transplantation; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Alemtuzumab

• Registration Number: NCT02529839
• Lead Sponsor: Hadassah Medical Organization

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2015-04
• Study First Submitted: 2015-06-10
• Study First Submitted QC: 2015-08-19
• Last Update Submitted: 2015-08-19
• Study First Posted: 2015-08-20
• Last Update Posted: 2015-08-20
• Study Start: 2015-10
• Primary Completion: 2017-10
• Study Completion: 2017-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Consenting patients fulfilling the Poser's clinical criteria for definite MS
2. Age: 18-65, males and females
3. Relapsing and secondary progressive forms of MS with evidence of significant activity of MS (clinical and on the MRI).
4. EDSS score of 2.0 to 7.0 (see table 1).
5. 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.
6. 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

1. 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).
2. Patients with active infections.
3. Patients with severe cognitive decline or inability to understand and sign the informed consent.
4. Patients who were treated with investigational protocols during the last 3 months prior to the inclusion.
5. Patients who received high dose immunosuppression with autologous stem cell rescue in the past with no effect.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental	Autologous bone marrow transplantation	Fludarabine 30mg/m2 for 4 days, Cyclophosphamide 50mg/kg for 2 days, Alemtuzumab administered subcutaneously 24mg total dose. Autologous bone marrow transplantation
Experimental	Fludarabine	Fludarabine 30mg/m2 for 4 days, Cyclophosphamide 50mg/kg for 2 days, Alemtuzumab administered subcutaneously 24mg total dose. Autologous bone marrow transplantation
Experimental	Cyclophosphamide	Fludarabine 30mg/m2 for 4 days, Cyclophosphamide 50mg/kg for 2 days, Alemtuzumab administered subcutaneously 24mg total dose. Autologous bone marrow transplantation
Experimental	Alemtuzumab	Fludarabine 30mg/m2 for 4 days, Cyclophosphamide 50mg/kg for 2 days, Alemtuzumab administered subcutaneously 24mg total dose. Autologous bone marrow transplantation

Primary Outcome Measures

Name	Time	Method
Engraftment parameters of Neutrophils and Platelets	1 year	Absolute Neutrophil count \>500 /microliter, Platelets\>20,000/microliter
Transplant related mortality by Day 100	Day 100

Secondary Outcome Measures

Name	Time	Method
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	1 year	Volume of gadolinium enhancing lesions