Multiple Sclerosis
Conditions
Brief summary
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.
Interventions
BIOLOGICALHematopoietic stem cell transplantation
Autologous hematopoietic stem cell transplantation
Sponsors
Northwestern University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Progression | 3 years after transplant | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival | three years | 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 |
Participant flow
Recruitment details
Between January 2003 and February 2005 in Northwestern Memorial Hospital 21 patients with relapsing-remitting multiple sclerosis (MS) underwent autologous hematopoietic stem cell transplantation in order to evaluate the safety and clinical outcome of autologous non-myeloablative hematopoetic stem cell transplantation in MS.
Pre-assignment details
21 eligible patients had relapsing remitting MS not responding to interferon and had had two corticosteroid -treated relapses within the previous 12 months or one relapse and gadolinium-enhancing lesions seen on MRI and separate from the relapse.
Participants by arm
| Arm | Count |
|---|---|
| Stem Cell Transplantation All participants will undergo stem cell transplantation after receiving conditioning regimen.
hematopoietic stem cell transplantation : Autologous hematopoietic stem cell transplantation | 21 |
| Total | 21 |
Baseline characteristics
| Characteristic | Stem Cell Transplantation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants |
| Age, Continuous | 21 years STANDARD_DEVIATION 2 |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 21 |
| serious Total, serious adverse events | 0 / 21 |
Outcome results
Primary
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.
Time frame: 3 years after transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stem Cell Transplantation | Disease Progression | 4 participants |
Secondary
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
Time frame: three years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stem Cell Transplantation | Survival | 21 participants |