Multiple Sclerosis, Relapsing-RemittingPhase 3MOSTNCT03342638
Maximizing Outcome of Multiple Sclerosis Transplantation
A Phase 3 study testing Cyclophosphamide, Mesna and rATG in people with Multiple Sclerosis, Relapsing-Remitting, run by Northwestern University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 58 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting
- What is being tested?
- Cyclophosphamide, Mesna and rATG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Nov 2017to 9 Oct 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 58 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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
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- 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
- Resting left ventricular ejection fraction (LVEF) < 50 %
- Bilirubin > 2.0 mg/dl
- Serum creatinine > 2.0 mg/dl
- Known hypersensitivity to mouse, rabbit, or E. Coli derived proteins or to iron compounds/medications
- Presence of metallic objects implanted in the body that would preclude the ability of the patient to safely have MRI exams
- Platelet count < 100,000/ul
- White blood cell count (WBC) < 1,500 cells/mm3
- Psychiatric illness, mental deficiency or cognitive dysfunction making compliance with treatment or informed consent impossible
- Active infection except asymptomatic bacteriuria
- Use of Tysabri (natalizumab) within the previous six months
- Use of Gilenya (fingolimod) within the previous three months
- Use of Tecfidera (dimethyl fumarate) within the previous three months
- Use of Aubagio (teriflunomide) 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
- Use of Lemtrada/Campath (alemtuzumab) within previous 12 months
- Use of Rituxan (rituximab) or Ocrevus (ocrelizumab) within previous four months
- Prior treatment with Novantrone (mitoxantrone)
- Any hereditary neurological disease such as Charcot-Marie-Tooth disease (CMT), Spinocerebellar ataxia (SCA), or Parkinson's Disease
- Severe or symptomatic cervical spinal stenosis unless surgically corrected
- Myocardial infarction within last 12 months; if longer than 12 months, must pass dobutamine stress test and be cleared by cardiology
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Maximizing Outcome of Multiple Sclerosis Transplantation: "MOST" Trial
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).
Read the detailed description
Multiple sclerosis (MS) is at onset an immune-mediated demyelinating disease. In most cases, it starts as a relapsing-remitting disease with distinct attacks and no symptoms between flares. Over years or decades, virtually all cases transition into a progressive disease in which insidious and slow neurologic deterioration occurs with or without acute flares. Relapsing-remitting disease is often responsive to immune suppressive or modulating therapies, while immune based therapies are generally ineffective in patients with a progressive clinical course. This clinical course and response to immune suppression, as well as neuropathology and neuroimaging studies, suggest that disease progression is associated with axonal atrophy. Disability correlates better with measures of axonal atrophy than immune mediated demyelination. Therefore, immune based therapies, in order to be effective, need to be started early in the disease course while MS is predominantly an immune-mediated and inflammatory disease. While current immune based therapies delay disability, no intervention has been proven to prevent progressive disability.The investigators propose a randomized study of autologous unmanipulated peripheral blood hematopoietic stem cell transplant (HSCT) comparing two different conditioning regimens: (1) cyclophosphamide and rabbit anti-thymoglobulin (rATG) versus (2) cyclophosphamide, rATG, and Intravenous Immunoglobulin (IVIg).
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Being tested
- Cyclophosphamide, Mesna, rATG, Methylprednisolone, G-CSF
- Keywords
- Autologous Stem Cell Transplantation, Stem Cells, Hematopoietic Stem Cell Transplantation
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Also called Cytoxan, Neosar
Potent immunosuppressive agent; an alkylating agent
MesnaDrug
Also called Mesnex
Medication used to decrease the risk of hemorrhagic cystitis prophylaxis
rATGDrug
Also called Thymoglobulin
A predominantly lymphocyte-specific immunosuppressive agent which contains antibodies specific to the antigens commonly found on the surface of T cells
Also called Solu-Medrol
Steroid
G-CSFDrug
Also called Neupogen, Filgrastim, Granix, Zarxio
Granulocyte-colony stimulating factor; a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream
IVIgBiological
Also called Gammagard, Carimune Nanofiltered (NF), Bivagam, Privigen
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).
Autologous Stem CellsBiological
Infusion of participant's own stem cells
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Cyclophosphamide; Drug: Mesna; Drug: rATG; Drug: Methylprednisolone; Drug: G-CSF; Biological: IVIg; Biological: Autologous Stem Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study start8 Nov 2017
- Primary completion23 Jul 2019
- Study completion9 Oct 2019
Why it stopped: PI Sabbatical
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Richard Burt, MD, Northwestern University
- Investigators
- Richard Burt, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03342638
- Sponsor's protocol ID
- DIAD.MOST.2017
- Acronym
- MOST
- Status last verified
- Jan 2021
- First submitted
- 9 Nov 2017
- Last updated
- 11 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Maximizing Outcome of Multiple Sclerosis Transplantation: "MOST" Trial
- ClinicalTrials.gov ID
- NCT03342638
- Acronym / sponsor ID
- MOST / DIAD.MOST.2017
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Keywords
- Autologous Stem Cell Transplantation, Stem Cells, Hematopoietic Stem Cell Transplantation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI Sabbatical
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- 8 Nov 2017 (actual)
- Primary completion
- 23 Jul 2019 (actual)
- Study completion
- 9 Oct 2019 (actual)
- First posted
- 17 Nov 2017 (actual)
- Results
- Posted 11 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Multiple sclerosis (MS) is at onset an immune-mediated demyelinating disease. In most cases, it starts as a relapsing-remitting disease with distinct attacks and no symptoms between flares. Over years or decades, virtually all cases transition into a progressive disease in which insidious and slow neurologic deterioration occurs with or without acute flares. Relapsing-remitting disease is often responsive to immune suppressive or modulating therapies, while immune based therapies are generally ineffective in patients with a progressive clinical course. This clinical course and response to immune suppression, as well as neuropathology and neuroimaging studies, suggest that disease progression is associated with axonal atrophy. Disability correlates better with measures of axonal atrophy than immune mediated demyelination. Therefore, immune based therapies, in order to be effective, need to be started early in the disease course while MS is predominantly an immune-mediated and inflammatory disease. While current immune based therapies delay disability, no intervention has been proven to prevent progressive disability.The investigators propose a randomized study of autologous unmanipulated peripheral blood hematopoietic stem cell transplant (HSCT) comparing two different conditioning regimens: (1) cyclophosphamide and rabbit anti-thymoglobulin (rATG) versus (2) cyclophosphamide, rATG, and Intravenous Immunoglobulin (IVIg).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control Arm | Experimental | Drug: Cyclophosphamide, Drug: Mesna, Drug: rATG, Drug: Methylprednisolone, Drug: G-CSF, Biological: Autologous Stem CellsHematopoietic 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. |
| IVIg Arm | Experimental | Drug: Cyclophosphamide, Drug: Mesna, Drug: rATG, Drug: Methylprednisolone, Drug: G-CSF, Biological: IVIg, Biological: Autologous Stem CellsHematopoietic 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. |
Who may qualify
- Ages
- 18 to 58 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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)
Key exclusion criteria (34 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CyclophosphamideAlso: Cytoxan, NeosarPotent immunosuppressive agent; an alkylating agent | Drug | Control Arm, IVIg Arm |
| MesnaAlso: MesnexMedication used to decrease the risk of hemorrhagic cystitis prophylaxis | Drug | Control Arm, IVIg Arm |
| rATGAlso: ThymoglobulinA predominantly lymphocyte-specific immunosuppressive agent which contains antibodies specific to the antigens commonly found on the surface of T cells | Drug | Control Arm, IVIg Arm |
| MethylprednisoloneAlso: Solu-MedrolSteroid | Drug | Control Arm, IVIg Arm |
| G-CSFAlso: Neupogen, Filgrastim, Granix, ZarxioGranulocyte-colony stimulating factor; a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream | Drug | Control Arm, IVIg Arm |
| IVIgAlso: Gammagard, Carimune Nanofiltered (NF), Bivagam, PrivigenSterile, 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). | Biological | IVIg Arm |
| Autologous Stem CellsInfusion of participant's own stem cells | Biological | Control Arm, IVIg Arm |
Primary outcome
Efficacy - Rate of Disease Activity
Time frame: 5 years
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Burt, MD principal investigator
Northwestern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cyclophosphamide, Mesna and rATG in people with Multiple Sclerosis, Relapsing-Remitting, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy - Rate of Disease Activity (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2021.