Hematopoietic Stem Cell Therapy for Patients with Inflammatory Multiple Sclerosis Failing Alternate Approved Therapy: A Randomized Study

Phase 1

• Conditions: Inflammatory Multiple Sclerosis; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2012-004165-41-GB
• Lead Sponsor: orthwestern University

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-09-19
• Study Completion: 2019-10-18
• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 0

Inclusion Criteria

1. Age between 18-55, inclusive
2. Diagnosis of MS using McDonald criteria of clinically definite MS
3. An EDSS of 2.0 to 6.0
4. Inflammatory disease despite treatment with standard disease modifying therapy including at least 6 months of interferon or copaxone. Inflammatory disease is defined based on both MRI (gadolinium enhancing lesions) and clinical activity (acute relapses *treated with IV or oral high dose corticosteroids and prescribed by a neurologist).
Minimum disease activity required for failure is defined as: a) two or more *steroid treated clinical relapses with documented new objective signs on neurological examination documented by a neurologist and treated with steroids within the year prior to the study, or b) one *steroid treated clinical relapse within the year prior to
study and evidence on MRI of active inflammation (i.e., gadolinium enhancement) within the last 12 months on an occasion separate from the clinical relapse (3 months before or after the clinical relapse).
*A steroid treated relapse will include a relapse that was severe enough to justify treatment but due to patient intolerance of steroids, or a history of nonresponse
to steroids, they were offered but not used.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

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 from the time of evaluation for eligibility until 6 months posttransplant (if on transplant) or until appropriate for nontransplant treatment (if on control arm). Effective birth control is defined as 1) abstinence defined as refraining from all acts of vaginal intercourse; 2) consistent use of birth control pills; 3) injectable birth control methods (Depoprovera,
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. FEV1/FVC < 60% of predicted after bronchodilator therapy (if necessary)
7. DLCO < 50% of predicted (for the transplant arm)
8. Resting 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 MS
14. Diagnosis of secondary progressive MS
15. Platelet count < 100,000/ul, WBC < 1,500 cells/mm3
16. Psychiatric illness, mental deficiency or cognitive dysfunction making compliance with treatment or informed consent impossible
17. Active infection except asymptomatic bacteriuria
18. Use of natalizumab (Tysabri) within the previous 6 months
19. Use of fingolimod (Gilenya) within the previous 3 months
20. Use of Teriflunomide (Aubagio) within the previous 2 years unless cleared from the body (plasma concentration < 0.02mcg/ml) following elimination from the body with cholestyramine 8g three times a day for 11 days
21. Prior treatment with CAMPATH (alemtuzumab)
22. Prior treatment with mitoxantrone
23. Any hereditary neurological disease such as CharcotMarieTooth disease (CMT) or Spinocerebellar ataxia (SCA) are contraindications
24. Use of tecfidera within the previous 3 months

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of autologous PBSCT versus standard of care [i.e. Tysabri (natalizumab), Gilenya (fingolimod) or Tecfidera (dimethyl fumarate)] in patients with inflammatory MS failing alternate approved therapy. <br><br>;Secondary Objective: N/A;Primary end point(s): Disease progression, defined as a 1-point increase in the EDSS on consecutive evaluations at least 6 months apart and not due to a non-MS disease process. Patients will be followed for 5 years after randomization.