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

Primary Purpose

Multiple Sclerosis

Status

Unknown status

Phase

Not Applicable

Locations

Study Type

Interventional

Intervention

Autologous bone marrow transplantation

Fludarabine

Cyclophosphamide

Alemtuzumab

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring MS, BMT

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental

Arm Description

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

Outcomes

Primary Outcome Measures

Engraftment parameters of Neutrophils and Platelets

Absolute Neutrophil count >500 /microliter, Platelets>20,000/microliter

Transplant related mortality by Day 100

Secondary Outcome Measures

Changes in the Expanded Disability Status Scale (EDSS score, as compared to baseline)

Overall survival (OS) at 1 year

Progression-free survival (PFS) at 1 year

Changes in MRI activity

T2 number

Changes in MRI activity

Volume of gadolinium enhancing lesions

Full Information

NCT ID

NCT02529839

First Posted

June 10, 2015

Last Updated

August 19, 2015

Sponsor

Hadassah Medical Organization

1. Study Identification

Unique Protocol Identification Number

NCT02529839

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2015

Overall Recruitment Status

Unknown status

Study Start Date

October 2015 (undefined)

Primary Completion Date

October 2017 (Anticipated)

Study Completion Date

October 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hadassah Medical Organization

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis

Keywords

MS, BMT

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Experimental

Arm Type

Experimental

Arm Description

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

Intervention Type

Procedure

Intervention Name(s)

Autologous bone marrow transplantation

Intervention Description

IMMUNOABLATIVE NONMYELOABLATIVE AUTOLOGOUS BONE MARROW TRANSPLANTATION on Day 0

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Intervention Description

30mg/m2 on days -6 through -3

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

50mg/kg on days -5 through -4

Intervention Type

Drug

Intervention Name(s)

Alemtuzumab

Intervention Description

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

Primary Outcome Measure Information:

Title

Engraftment parameters of Neutrophils and Platelets

Description

Absolute Neutrophil count >500 /microliter, Platelets>20,000/microliter

Time Frame

1 year

Title

Transplant related mortality by Day 100

Time Frame

Day 100

Secondary Outcome Measure Information:

Title

Changes in the Expanded Disability Status Scale (EDSS score, as compared to baseline)

Time Frame

1 year

Title

Overall survival (OS) at 1 year

Time Frame

1 year

Title

Progression-free survival (PFS) at 1 year

Time Frame

1 year

Title

Changes in MRI activity

Description

T2 number

Time Frame

1 year

Title

Changes in MRI activity

Description

Volume of gadolinium enhancing lesions

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Igor Resnick, Prof.

Phone

972-50-787-4663

gashka.resnick@gmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Igor Resnick, Prof.

Organizational Affiliation

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

Official's Role

Principal Investigator

12. IPD Sharing Statement

Learn more about this trial

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

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