NCT02674217

Brief Summary

Multiple sclerosis (MS) is a chronic, inflammatory, debilitating disease that causes destruction of central nervous system (CNS) myelin, with varying degrees of axonal damage. It mainly affects young adults and is twice as common in women as in men (1). Studies published from the 1990s brought animal models and theoretical considerations of hematopoietic stem cell transplantation (HSCT) being useful in the prevention and treatment of autoimmune diseases, with clinical responses in some patients, suggesting that high-dose chemotherapy followed by HSCT rescue could "reset" the immunological changes through the control of autoreactive clones, followed by immunological tolerance after immune reconstitution (2); this led to the conclusion that HSCT may be a viable therapeutic option for MS (1-6). Autologous HSCT have been done in patients with MS since 1996 and more than 700 HSCTs have been performed around the world (1-6). Most patients have been treated in small trials or in multicenter studies. In retrospective analyzes, a progression-free survival of more than five years after transplant has been observed, the neurological outcomes being considerably more favorable in patients with the relapsing-remitting type and/or those who showed an inflammatory pattern in magnetic resonance imaging (MRI) during the pre-transplant screening. Reports of good results, particularly in the aggressive forms of MS reinforce the effectiveness HSCT in MS patients with prominent inflammatory activity. The risk of transplant related mortality in HSCT for MS was conventionally considered very high but has declined since 2001 to 1.3% (2-6), this probably being the result of the changes in the conditioning regimens, thus reducing toxicity. Recent data, with more than 700 autologous transplants for MS in Europe, showed an overall survival of 92% in five years and a progression-free survival of 46%, the main cause of mortality and morbidity being the recurrence of the autoimmune disease (2-6). The consensus provides an indication of HSCT in patients with progressive MS unresponsive to conventional therapy and Expanded Disability Status Scale (EDSS) (1) between 3.0 and 6.0. The forms of the disease that might benefit from transplantation are: relapsing remitting, primary or secondary progressive, and the "malignant" form, provided there is evidence of inflammatory activity at the time of transplant indication.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
1,000

participants targeted

Target at P75+ for not_applicable multiple-sclerosis

Timeline
Completed

Started May 2015

Longer than P75 for not_applicable multiple-sclerosis

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2015

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

August 31, 2015

Completed
5 months until next milestone

First Posted

Study publicly available on registry

February 4, 2016

Completed
9.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2025

Completed
Last Updated

September 7, 2023

Status Verified

September 1, 2023

Enrollment Period

10.6 years

First QC Date

August 31, 2015

Last Update Submit

September 5, 2023

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

  • Expanded Disability Status Scale

    EDSS

    4 years

Secondary Outcomes (1)

  • Overall survival

    4 years

Study Arms (1)

Multiple sclerosis autografted patients

EXPERIMENTAL

Individuals with a relapsing-remitting (RRMS) course, secondary progressive (SPMS) or primary progressive (PPMS) were included. Patients should have a Karnofsky performance status (18) above 70% and a EDSS score (1) of 6 or below. The study is approved by the Etichs Committee of the Clinica RUIZ and all patients signed a consent form after being fully informed about procedure an possible complications. Patients included will de treated with Hematopoietic stem cell transplantation

Procedure: Hematopoietic stem cell transplantation

Interventions

Hematopoietic stem cell transplantationPROCEDURE

autologous transplant using non-frozen peripheral blood stem cells

Also known as: autologous transplant
Multiple sclerosis autografted patients

Eligibility Criteria

Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with MS having a relapsing-remitting course, even though other forms could also qualify: Secondary progressive (SPMS) or primary progressive (PPMS)
  • Patients must have a Karnofsky performance status above 70% and a EDSS score of 8 or below.
  • In cases of patients with score between 6 and 8 patients will be accepted provided a carer accompanies the patient.
  • A recent central nervous system (CNS) MRI study (less than two months).
  • Patient has to be able to travel to and remain in Puebla, México during an 4-week period, accompanied by a caregiver.
  • Discontinue Immune Modulation or suppression medications 3 months before.

You may not qualify if:

  • EDSS score higher than 8
  • Karnofsky performance status lower than 70%
  • Been exposed to chemotherapy in the past

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (5)

  • Gale RP, Gomez-Cruz GB, Olivares-Gazca JC, Leon-Pena AA, Gomez-Almaguer D, Gomez-De-Leon A, Gonzalez-Lopez EE, Ruiz-Arguelles A, Soto-Vega E, Munoz-Perez MJ, Ruiz-Delgado GJ, Ruiz-Arguelles GJ. Determine safety of outpatient chemotherapy and autotransplants using refrigerated, non-frozen grafts in persons with multiple sclerosis. Clin Transplant. 2019 Jun;33(6):e13567. doi: 10.1111/ctr.13567. Epub 2019 May 7.

    PMID: 31004516BACKGROUND

  • Ruiz-Arguelles GJ, Leon-Pena AA, Leon-Gonzalez M, Nunez-Cortes AK, Olivares-Gazca JC, Murrieta-Alvarez I, Vargas-Espinosa J, Medina-Ceballos E, Cantero-Fortiz Y, Ruiz-Arguelles A, Ruiz-Delgado MA, Ruiz-Delgado RJ, Ruiz-Reyes G, Priesca-Marin M, Torres-Priego MS, Blumenkron-Marroquin D, Ruiz-Delgado GJ. A Feasibility Study of the Full Outpatient Conduction of Hematopoietic Transplants in Persons with Multiple Sclerosis Employing Autologous Non-Cryopreserved Peripheral Blood Stem Cells. Acta Haematol. 2017;137(4):214-219. doi: 10.1159/000469655. Epub 2017 May 18.

    PMID: 28514773RESULT

  • Ruiz-Arguelles GJ, Olivares-Gazca JC, Olivares-Gazca M, Leon-Pena AA, Murrieta-Alvarez I, Cantero-Fortiz Y, Gomez-Cruz GB, Ruiz-Arguelles A, Priesca-Marin M, Ruiz-Delgado GJ. Self-reported changes in the expanded disability status scale score in patients with multiple sclerosis after autologous stem cell transplants: real-world data from a single center. Clin Exp Immunol. 2019 Dec;198(3):351-358. doi: 10.1111/cei.13358. Epub 2019 Aug 19.

    PMID: 31394007RESULT

  • Hernandez-Flores EJ, Gallardo-Perez MM, Robles-Nasta M, Montes-Robles MA, Sanchez-Bonilla D, Pastelin-Martinez ML, Ocana-Ramm G, Olivares-Gazca JC, Ruiz-Delgado GJ, Ruiz-Arguelles GJ. Second Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis: A Single-Center Prospective Experience. Transplant Proc. 2024 Jan-Feb;56(1):211-214. doi: 10.1016/j.transproceed.2023.12.004. Epub 2024 Jan 4.

    PMID: 38177042DERIVED

  • Montes-Robles MA, Gallardo-Perez MM, Hernandez-Flores EJ, Pastelin-Martinez ML, Sanchez-Bonilla D, Robles-Nasta M, Ocana-Ramm G, Olivares-Gazca JC, Ruiz-Delgado GJ, Ruiz-Arguelles GJ. In persons with CIDP, auto-HSCT can be conducted fully on an outpatient basis and induces significant clinical responses: A prospective study in a single center. Transpl Immunol. 2023 Dec;81:101944. doi: 10.1016/j.trim.2023.101944. Epub 2023 Oct 20.

    PMID: 37866669DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Hematopoietic Stem Cell TransplantationTransplantation, Autologous

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

Stem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, Operative

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director

Study Record Dates

First Submitted

August 31, 2015

First Posted

February 4, 2016

Study Start

May 1, 2015

Primary Completion

December 1, 2025

Study Completion

December 1, 2025

Last Updated

September 7, 2023

Record last verified: 2023-09

Data Sharing

IPD Sharing
Will not share