Hematopoietic Stem Cell Therapy for Patients With Multiple Sclerosis

Hematopoietic Stem Cell Therapy for Patients With Inflammatory Multiple Sclerosis Failing Interferon Therapy: A Phase II Multi-Center Trial

Multiple sclerosis is disease believed to be due to immune cells, cells which normally protect the body, but are now attacking the tissue in the brain and possibly the spinal cord. The likelihood of progression of this disease is high. This study is designed to examine whether treating patients with high dose cyclophosphamide and CAMPATH-1H (drugs which reduce the function of the immune system) followed by return of previously collected blood stem cells will stop the progression of your multiple sclerosis. Stem cells are undeveloped cells that have the capacity to grow into mature blood cells, which normally circulate in the blood stream. The purpose of the cyclophosphamide and CAMPATH-1H is to destroy the cells in your immune system which are thought to be causing your disease. The purpose of the stem cell infusion is to restore the body's blood production, which will be severely impaired by the high dose chemotherapy and to produce a normal immune system that will no longer attack the body.

Study Overview

• Status: Terminated
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Biological: Hematopoietic stem cell transplantation

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age between 18-50, inclusive.
2. Diagnosis of Multiple Sclerosis (MS) using Poser criteria (Appendix A).
3. An Expanded Disability Status Scale (EDSS) of 2.0 - 5.5 (Appendix B).
4. Inflammatory disease despite primary disease modifying therapy with at least 3 months of interferon. Failure is defined as two or more clinical relapses with documented neurologic changes within the year prior to the study. (NOTE: Relapses must have required treatment with corticosteroids. Sensory only relapses are excluded.) Failure may also be defined as one relapse within the year prior to study if there is evidence on MRI of active inflammation (i.e., gadolinium enhancement).

Exclusion Criteria:

1. Any illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive chemotherapy.
2. Prior history of malignancy except localized basal cell, squamous skin cancer or carcinoma in situ of the cervix. Other malignancies for which the patient is judged to be cured, such as head and neck cancer, or breast cancer will be considered on an individual basis.
3. Positive pregnancy test.
4. Inability or unwillingness to pursue effective means of birth control. Effective birth control is defined as 1) refraining from all acts of vaginal intercourse (ABSTINENCE); 2) consistent use of birth control pills; 3) injectable birth control methods (Depo-provera, Norplant); 4) tubal sterilization or male partner who has undergone vasectomy; 5) placement of an intrauterine device (IUD); or 6) use, with every act of intercourse, of diaphragm with contraceptive jelly and/or condoms with contraceptive foam.
5. Failure to willingly accept or comprehend irreversible sterility as a side effect of therapy.
6. Forced expiratory volume in 1 second (FEV1) / forced vital capacity (FVC) < 60% of predicted after bronchodilator therapy (if necessary).
7. Diffusing capacity of the lung for carbon monoxide (DLCO) < 50% of predicted.
8. Resting left ventricular ejection fraction (LVEF) < 50 %.
9. Bilirubin > 2.0 mg/dl.
10. Serum creatinine > 2.0 mg/dl.
11. Known hypersensitivity to mouse, rabbit, or E. Coli derived proteins, or to iron compounds/medications.
12. Presence of metallic objects implanted in the body that would preclude the ability of the patient to safely have MRI exams.
13. Diagnosis of primary progressive multipole sclerosis (MS).
14. Platelet count < 100,000/ul.
15. Psychiatric illness, mental deficiency or cognitive dysfunction making compliance with treatment or informed consent impossible.
16. Active infection except asymptomatic bacteruria.

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: Hematopoietic stem cell transplantation; All participants will undergo hematopoietic stem cell transplantation after receiving conditioning regimen.	Biological: Hematopoietic stem cell transplantation; Autologous hematopoietic stem cell transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Progression	Data are reporting number of participants with disease progression. Disease progression is defined as a 1 point increase in the Expanded Disability Status Scale (EDSS) on consecutive evaluations at least 3 months apart.	3 years after transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	Data are reporting the number of participants who survived three years after the transplant Survival of 21 participants was evaluated at three years after the transplant	three years

Collaborators and Investigators

• Sponsor: Northwestern University

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: January 16, 2006
• First Submitted That Met QC Criteria: January 16, 2006
• First Posted (Estimate): January 18, 2006

Study Record Updates

• Last Update Posted (Estimate): May 1, 2014
• Last Update Submitted That Met QC Criteria: March 31, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• 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
• Other Study ID Numbers: DIAD MS.Auto2002