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

NCT02529839 | Unknown

• 1 other identifier: 0105-15-HMO-CTIL
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Multiple Sclerosis

Keywords

MS; BMT

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• 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

• Changes in MRI activity

  1 year

Study Arms (1)

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; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Alemtuzumab

Interventions

Autologous bone marrow transplantation PROCEDURE

IMMUNOABLATIVE NONMYELOABLATIVE AUTOLOGOUS BONE MARROW TRANSPLANTATION on Day 0

Experimental

Fludarabine DRUG

30mg/m2 on days -6 through -3

Experimental

Cyclophosphamide DRUG

50mg/kg on days -5 through -4

Experimental

Alemtuzumab DRUG

3mg on day -3, 9mg on day -2, 12 mg on day -1

Experimental

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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 received high dose immunosuppression with autologous stem cell rescue in the past with no effect.

Sponsors & Collaborators

• Hadassah Medical Organization: lead

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

fludarabine; Cyclophosphamide; Alemtuzumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Igor Resnick, Prof.

  Bone Marrow Transplantation, Cancer Immunotherapy & Immunobiology Research Center, Hadassah University Hospital, Ein Kerem, Jerusalem, Israel

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Igor Resnick, Prof.

CONTACT

972-50-787-4663; gashka.resnick@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2015
• First Posted: August 20, 2015
• Study Start: October 1, 2015
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: August 20, 2015

Record last verified: 2015-04