Stem Cell Therapy for Patients With Multiple Sclerosis Failing Alternate Approved Therapy- A Randomized Study

• ClinicalTrials.gov Identifier: NCT00273364
• Recruitment Status: Completed
• First Posted: January 9, 2006
• Results First Posted: August 12, 2020
• Last Update Posted: August 12, 2020
• Sponsor: Northwestern University
• Collaborators: Uppsala University; Sheffield Teaching Hospitals NHS Foundation Trust; University of Sao Paulo
• Information provided by (Responsible Party): Richard Burt, MD, Northwestern University

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Sclerosis
• Interventions: Procedure: Hematopoietic Stem Cell Therapy; Drug: Standard treatment with a conventional drug
• Enrollment: 110

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Hematopoietic Stem Cell Transplantation	Standard Therapy for MS
Arm/Group Description	Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with Cyclophosphamide and rATG Hematopoietic Stem Cell Therapy: After mobilization and harvest of stem cells, stem cells will be infused following conditioning regimen	Standard treatment with a conventional drug is the treatment with one of the following drugs: Avonex (interferon beta 1a), Betaseron (interferon beta 1b), Copaxone (glatiramer acetate), Aubagio (teriflunomide), Tysabri (natalizumab), Gilenya (fingolimod) or Dimethyl fumarate (Tecfidera or BG-12) Standard treatment with a conventional drug: Standard treatment with a conventional drug is the treatment with one of the following drugs: Avonex (interferon beta 1a), Betaseron (interferon beta 1b), Copaxone (glatiramer acetate), Aubagio (teriflunomide), Tysabri (natalizumab), or Gilenya (fingolimod)
Period Title: Overall Study
Started	55	55
Completed	55	55
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Hematopoietic Stem Cell Transplantation	Standard Therapy for MS	Total
Arm/Group Description		Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with Cyclophosphamide and rATG Hematopoietic Stem Cell Therapy: After mobilization and harvest of stem cells, stem cells will be infused following conditioning regimen	Standard treatment with a conventional drug is the treatment with one of the following drugs: Avonex (interferon beta 1a), Betaseron (interferon beta 1b), Copaxone (glatiramer acetate), Aubagio (teriflunomide), Tysabri (natalizumab), Gilenya (fingolimod) or Dimethyl fumarate (Tecfidera or BG-12) Standard treatment with a conventional drug: Standard treatment with a conventional drug is the treatment with one of the following drugs: Avonex (interferon beta 1a), Betaseron (interferon beta 1b), Copaxone (glatiramer acetate), Aubagio (teriflunomide), Tysabri (natalizumab), or Gilenya (fingolimod)	Total of all reporting groups
Overall Number of Baseline Participants		55	55	110
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	55 participants	55 participants	110 participants
		35.6; (18 to 54)	35.6; (19 to 52)	35.6; (18 to 54)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	55 participants	55 participants	110 participants
	Female	34 61.8%	39 70.9%	73 66.4%
	Male	21 38.2%	16 29.1%	37 33.6%
Expanded Disability Status Scale (EDSS) [1] [2]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	52 participants	54 participants	106 participants
		3.4 (1.2)	3.3 (1.0)	3.35 (.05)
		[1] Measure Description: The EDSS provides a total disability score on a scale that ranges from 0 (no disability) to 10 (worst neurologic disability).; [2] Measure Analysis Population Description: The number analyzed in rows differs from the overall enrolled because EDSS were not analyzed on patients who did not receive intervention or who were lost to follow up.

Outcome Measures

1. Primary Outcome

Title	Expanded Disability Status Scale (EDSS) Improvement
Description	The EDSS scale ranges from 0 to 10 in 0.5 increments that represent higher levels of disability. Improvement in EDSS is defined by both a 0.5 or 1.0 points sustained for more than 6 months.
Time Frame	Pre Treatment, 6 and 12 months Post Treatment

Outcome Measure Data

Analysis Population Description

The number analyzed in one or more rows differs from the overall number analyzed because not all patients had their EDSS evaluated and some patients were lost to followed up.

Arm/Group Title		Hematopoietic Stem Cell Transplantation	Standard Therapy for MS
Arm/Group Description:		Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with Cyclophosphamide and rATG Hematopoietic Stem Cell Therapy: After mobilization and harvest of stem cells, stem cells will be infused following conditioning regimen	Standard treatment with a conventional drug is the treatment with one of the following drugs: Avonex (interferon beta 1a), Betaseron (interferon beta 1b), Copaxone (glatiramer acetate), Aubagio (teriflunomide), Tysabri (natalizumab), Gilenya (fingolimod) or Dimethyl fumarate (Tecfidera or BG-12) Standard treatment with a conventional drug: Standard treatment with a conventional drug is the treatment with one of the following drugs: Avonex (interferon beta 1a), Betaseron (interferon beta 1b), Copaxone (glatiramer acetate), Aubagio (teriflunomide), Tysabri (natalizumab), or Gilenya (fingolimod)
Overall Number of Participants Analyzed		52	54
Mean (Standard Deviation); Unit of Measure: units on a scale
Pre Treatment	Number Analyzed	52 participants	54 participants
		3.4 (1.2)	3.3 (1.0)
6 Months Post Treatment	Number Analyzed	52 participants	54 participants
		2.5 (1.4)	3.7 (1.5)
12 Months Post Treatment	Number Analyzed	50 participants	48 participants
		2.4 (1.4)	4 (1.7)

Adverse Events

Time Frame	Adverse events were collected during transplant and at 1 year post Treatment
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Hematopoietic Stem Cell Transplantation		Standard Therapy for MS
Arm/Group Description	Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with Cyclophosphamide and rATG Hematopoietic Stem Cell Therapy: After mobilization and harvest of stem cells, stem cells will be infused following conditioning regimen		Standard treatment with a conventional drug is the treatment with one of the following drugs: Avonex (interferon beta 1a), Betaseron (interferon beta 1b), Copaxone (glatiramer acetate), Aubagio (teriflunomide), Tysabri (natalizumab), Gilenya (fingolimod) or Dimethyl fumarate (Tecfidera or BG-12) Standard treatment with a conventional drug: Standard treatment with a conventional drug is the treatment with one of the following drugs: Avonex (interferon beta 1a), Betaseron (interferon beta 1b), Copaxone (glatiramer acetate), Aubagio (teriflunomide), Tysabri (natalizumab), or Gilenya (fingolimod)
All-Cause Mortality
	Hematopoietic Stem Cell Transplantation		Standard Therapy for MS
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/52 (0.00%)		0/55 (0.00%)
Serious Adverse Events
	Hematopoietic Stem Cell Transplantation		Standard Therapy for MS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/52 (0.00%)		0/55 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Hematopoietic Stem Cell Transplantation		Standard Therapy for MS
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/52 (32.69%)		0/55 (0.00%)
General disorders
Febrile Neutropenia (culture negative) †	13/52 (25.00%)	13	0/55 (0.00%)	0
Metabolism and nutrition disorders
Hypophosphatemia †	17/52 (32.69%)	17	0/55 (0.00%)	0
Hypokalemia †	13/52 (25.00%)	13	0/55 (0.00%)	0
Hypergylcemia †	5/52 (9.62%)	5	0/55 (0.00%)	0
† Indicates events were collected by systematic assessment

Limitations and Caveats

Limitations to the study are the relatively small number of patients who were treated compared with pharmaceutical sponsored trials, and the relatively small sample size resulted in small numbers of patients available to assess longer term outcomes.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Kathleen Quigley
• Organization: Northwestern University
• Phone: 312-695-8192
• EMail: k-quigley@northwestern.edu

Publications of Results:

Burt RK, Balabanov R, Burman J, Sharrack B, Snowden JA, Oliveira MC, Fagius J, Rose J, Nelson F, Barreira AA, Carlson K, Han X, Moraes D, Morgan A, Quigley K, Yaung K, Buckley R, Alldredge C, Clendenan A, Calvario MA, Henry J, Jovanovic B, Helenowski IB. Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression in Patients With Relapsing-Remitting Multiple Sclerosis: A Randomized Clinical Trial. JAMA. 2019 Jan 15;321(2):165-174. doi: 10.1001/jama.2018.18743.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Burman J, Fransson M, Totterman TH, Fagius J, Mangsbo SM, Loskog AS. T-cell responses after haematopoietic stem cell transplantation for aggressive relapsing-remitting multiple sclerosis. Immunology. 2013 Oct;140(2):211-9. doi: 10.1111/imm.12129.

• Responsible Party: Richard Burt, MD, Northwestern University
• ClinicalTrials.gov Identifier: NCT00273364
• Obsolete Identifiers: NCT03133403
• Other Study ID Numbers: DI MS.Randomized2004
• First Submitted: January 5, 2006
• First Posted: January 9, 2006
• Results First Submitted: July 15, 2020
• Results First Posted: August 12, 2020
• Last Update Posted: August 12, 2020