Maximizing Outcome of Multiple Sclerosis Transplantation

NCT03342638 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: DIAD.MOST.2017
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized study of autologous un-manipulated peripheral blood hematopoietic stem cell transplant (HSCT) comparing two regimens: (1) cyclophosphamide and rabbit anti-thymoglobulin (rATG) versus (2) cyclophosphamide, rATG, and Intravenous Immunoglobulin (IVIg).

Conditions

Multiple Sclerosis, Relapsing-Remitting

Keywords

Autologous Stem Cell Transplantation; Stem Cells; Hematopoietic Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• Efficacy - Rate of Disease Activity

  Defined as no relapse (defined as acute neurologic deterioration occurring after engraftment and lasting more than 24 hours, accompanied by objective worsening on neurological examination that are documented by a neurologist and not explained by fever, infection, stress, heat or related pseudoexacerbation; supportive confirmation by enhancement on MRI is preferred), no disease progression (defined as a 1.0-point increase in the Expanded Disability Status Scale (EDSS) on consecutive evaluations at least 6 months apart and not due to a non-MS disease process), and no new or enhancing lesions on MRI

  5 years

Study Arms (2)

Control Arm

EXPERIMENTAL

Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with cyclophosphamide, mesna, rATG (rabbit), and methylprednisolone. Granulocyte-colony stimulating factor (G-CSF) will be administered post-transplant.

Drug: Cyclophosphamide; Drug: Mesna; Drug: rATG; Drug: Methylprednisolone; Drug: G-CSF; Biological: Autologous Stem Cells

IVIg Arm

EXPERIMENTAL

Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with cyclophosphamide, mesna, rATG (rabbit), and methylprednisolone. IVIg and G-CSF will be administered post-transplant.

Drug: Cyclophosphamide; Drug: Mesna; Drug: rATG; Drug: Methylprednisolone; Drug: G-CSF; Biological: IVIg; Biological: Autologous Stem Cells

Interventions

Cyclophosphamide DRUG

Potent immunosuppressive agent; an alkylating agent

Also known as: Cytoxan, Neosar

Control Arm; IVIg Arm

Mesna DRUG

Medication used to decrease the risk of hemorrhagic cystitis prophylaxis

Also known as: Mesnex

Control Arm; IVIg Arm

rATG DRUG

A predominantly lymphocyte-specific immunosuppressive agent which contains antibodies specific to the antigens commonly found on the surface of T cells

Also known as: Thymoglobulin

Control Arm; IVIg Arm

Methylprednisolone DRUG

Steroid

Also known as: Solu-Medrol

Control Arm; IVIg Arm

G-CSF DRUG

Granulocyte-colony stimulating factor; a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream

Also known as: Neupogen, Filgrastim, Granix, Zarxio

Control Arm; IVIg Arm

IVIg BIOLOGICAL

Sterile, purified immunoglobulin G (IgG) products manufactured from pooled human plasma and typically contain more than 95% unmodified IgG, which has intact Fc-dependent effector functions and only trace amounts of immunoglobulin A (IgA) or immunoglobulin M (IgM).

Also known as: Gammagard, Carimune Nanofiltered (NF), Bivagam, Privigen

IVIg Arm

Autologous Stem Cells BIOLOGICAL

Infusion of participant's own stem cells

Control Arm; IVIg Arm

Eligibility Criteria

• Age: 18 Years - 58 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 18-58 years
• Diagnosis of MS using revised McDonald criteria of clinically definite MS (Appendix A)
• An EDSS score of 2.0 to 6.0 (Appendix B).
• An EDSS \>6.0 may be included if still relapsing-remitting disease and at least two enhancing lesions on MRI within the last three months
• Inflammatory disease despite treatment with standard disease modifying therapy (DMT) including at least 6 months of interferon or Copaxone. Inflammatory disease is defined based on either MRI (gadolinium enhancing lesion, new T2 lesion) or \*steroid-treated clinical relapses (prescribed by a neurologist)
• Minimum disease activity required:
• Failed a first line DMT (Copaxone or Interferon), defined as two or more \*steroid treated clinical relapses within the last 12 months. A clinical relapse may also be evidence of active inflammation on MRI (gadolinium enhancing lesion or new T2 lesion) in the last 12 months on two MRIs at least three months apart
• Failed a second or third line MS Drug: Zinbryta (daclizumab), Aubagio (teriflunomide), Gilenya (fingolimod), Tecifidera (dimethyl fumarate), Lemtrada (alemtuzumab), Ocrevus (ocrelizumab), Tysabri (natalizumab), Rituxan (rituximab) or IVIg, defined as one \*steroid treated clinical relapse within the last 12 months or evidence of active inflammation on MRI (gadolinium enhancing lesion or new T2 lesion) in the last 12 months.
• Cognitive dysfunction that prevents gainful employment, but competent to comply with treatment and informed consent
• A steroid-treated relapse will include a relapse that was severe enough to justify treatment but due to patient intolerance of steroids, they were offered but not used.

You may not qualify if:

• Any adult who is unable to consent (for adults who are cognitively impaired due to MS, consent may be obtained from the closest living relative or person who has power of attorney)
• Individuals under the age of 18 or over the age of 58
• Diagnosis of Primary Progressive MS, Secondary Progressive MS, or Clinically Isolated Syndrome (CIS)
• Pregnant women (positive serum or urine human chorionic gonadotropin (HCG) test)
• Women who are breastfeeding
• Prisoners
• Any illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive chemotherapy
• Prior history of malignancy except localized basal cell, squamous skin cancer or carcinoma in situ of the cervix
• Any prior chemotherapy or radiation therapy (except for cyclophosphamide used to treat MS disease)
• History of sickle cell disease (SS), SC disease, coagulopathy, or if actively receiving anticoagulation therapy
• History of insulin-dependent diabetes
• Inability or unwillingness to pursue effective means of birth control from the time of evaluation for eligibility until 6 months post-transplant. 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 (Depo-provera, Norplant), (4) tubal sterilization or male partner who has undergone vasectomy, (5) placement of an intrauterine device (IUD), or (6) with every act of intercourse, use of diaphragm with contraceptive jelly and/or use of condom with contraceptive foam
• Failure to willingly accept or comprehend irreversible sterility as a side effect of therapy
• Forced expiratory volume at one second (FEV1)/ forced vital capacity (FVC) \< 60% of predicted after bronchodilator therapy (if necessary)
• Diffusing capacity of the lungs for carbon monoxide (DLCO) \< 60% of predicted

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Cyclophosphamide; Mesna; thymoglobulin; Methylprednisolone; Methylprednisolone Hemisuccinate; Granulocyte Colony-Stimulating Factor; Filgrastim; Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Kathleen Quigley
• Organization: Northwestern University

k-quigley@northwestern.edu

312-695-8192

Study Officials

• Richard Burt, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 9, 2017
• First Posted: November 17, 2017
• Study Start: November 8, 2017
• Primary Completion: July 23, 2019
• Study Completion: October 9, 2019
• Last Updated: January 11, 2021
• Results First Posted: January 11, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)