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

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

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.

Study Overview

• Status: Unknown
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Procedure: Autologous bone marrow transplantation; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Alemtuzumab

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; 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; IMMUNOABLATIVE NONMYELOABLATIVE AUTOLOGOUS BONE MARROW TRANSPLANTATION on Day 0; Drug: Fludarabine; 30mg/m2 on days -6 through -3; Drug: Cyclophosphamide; 50mg/kg on days -5 through -4; Drug: Alemtuzumab; 3mg on day -3, 9mg on day -2, 12 mg on day -1

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hadassah Medical Organization
• Investigators: Principal Investigator: Igor Resnick, Prof., Bone Marrow Transplantation, Cancer Immunotherapy & Immunobiology Research Center, Hadassah University Hospital, Ein Kerem, Jerusalem, Israel

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Anticipated): October 1, 2017
• Study Completion (Anticipated): October 1, 2017

Study Registration Dates

• First Submitted: June 10, 2015
• First Submitted That Met QC Criteria: August 19, 2015
• First Posted (Estimate): August 20, 2015

Study Record Updates

• Last Update Posted (Estimate): August 20, 2015
• Last Update Submitted That Met QC Criteria: August 19, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: MS; BMT
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Cyclophosphamide; Fludarabine; Alemtuzumab
• Other Study ID Numbers: 0105-15-HMO-CTIL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No