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

Hadassah Medical Center

Status: Unknown

Conditions: Multiple Sclerosis

Treatments: Drug: Alemtuzumab; Procedure: Autologous bone marrow transplantation; Drug: Fludarabine; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Other

Identifiers

NCT02529839

0105-15-HMO-CTIL

Details and patient eligibility

About

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.

Enrollment: 20 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

Experimental

Experimental group

Description:

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

Treatment:

Drug: Alemtuzumab

Procedure: Autologous bone marrow transplantation

Drug: Cyclophosphamide

Drug: Fludarabine