Neuromyelitis OpticaPhase 2/3ATTENDNCT03829566
Autologous Transplant To End NMO Spectrum Disorder
A Phase 2/3 study testing Rituximab, Cyclophosphamide and Mesna in people with Neuromyelitis Optica and Devic's Disease, run by Northwestern University at 2 sites in United States.
Trial summary
This study is designed to treat your disease with an autologous stem cell transplant using a regimen of immune suppressant drugs and chemotherapy to reset your immune system and to determine if your disease will go into long-term remission. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Neuromyelitis Optica, Devic's Disease, NMO Spectrum Disorder
- What is being tested?
- Rituximab, Cyclophosphamide and Mesna
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 2019to 28 Nov 2025
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 - 65 years old at the time of pre-transplant evaluation
- An established diagnosis of NMOSD (with or without aquaporin 4 (AQP4)-IgG antibody)
Who cannot join
- Under age of 18 or over age of 65
- Prisoners
- Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible, or any adult who is unable to consent (for adults cognitively impaired due to disease, consent may be obtained from the closest living relative).
- Paraplegia or quadriplegia (must be able to use a walker if even for only a few feet)
- Extensive subcortical white matter lesions
- Uncontrolled diabetes mellitus or any other illness that in the opinion of the investigators would jeopardize the ability of the patient to tolerate aggressive treatment
Show all 30Show fewer
- Myocardial infarction within the last 12 months. If longer than 12 months, must pass a dobutamine stress test and be cleared by cardiology.
- Active systemic lupus erythematous, Sjogren's, myasthenia gravis, or another autoimmune disease
- Sickle cell disease, sickle cell disease, or coagulopathy
- Prior history of malignancy that required any radiotherapy, chemotherapy, or biological therapy
- Positive pregnancy test, inability or unable to pursue effective means of birth control, or failure to willingly accept or comprehend irreversible sterility as a side effect of therapy
- Women who are breastfeeding
- Untreated life-threatening cardiac arrhythmia on electrocardiogram (EKG) or 24-hour holter
- Left ventricular ejection fraction (LVEF) <50%
- Tiffeneau-Pinelli index (FEV1/FVC) <70% of predicted after bronchodilator therapy (if necessary), or diffusing capacity of lung for carbon monoxide (DLCO) hemoglobin corrected <70 % predicted
- Serum creatinine >2.0 mg/dl
- Liver cirrhosis, transaminases >2x of normal limits, or bilirubin >2.0 mg/dl unless due to Gilbert's disease
- Major hematological abnormalities such as platelet count < 100,000/μl or absolute neutrophil count (ANC) < 1000/μl
- Active infection except asymptomatic bacteriuria
- Presence of metallic objects implanted in the body that would preclude the ability of the patient to safely have magnetic resonance imaging (MRI) exams
- Known hypersensitivity to mouse, rabbit, or E. coli derived proteins
- Human immunodeficiency virus (HIV) positive
- Hepatitis B or C positive
- Use of natalizumab (Tysabri) within the previous six months
- Use of fingolimod (Gilenya) within the previous three months
- Use of dimethyl fumarate (Tecfidera) within the previous three months
- Use of teriflunomide (Aubagio) 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 alemtuzumab (Lemtrada/Campath) within previous 12 months
- Use of rituximab (Rituxan) or ocrelizumab (Ocrevus) within previous six months
- Prior treatment with mitoxantrone (Novantrone)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Northwestern University, Feinberg School of Medicine
Chicago, Illinois, 60611
Northwestern University
Chicago, Illinois, 60611
About this study
Official title: Autologous Hematopoietic Stem Cell Transplant for Neuromyelitis Optica Spectrum Disorder (NMOSD)
This study is designed to treat your disease with an autologous stem cell transplant using a regimen of immune suppressant drugs and chemotherapy to reset your immune system and to determine if your disease will go into long-term remission.
Read the detailed description
The autologous stem cell transplant used in this research study is an investigational procedure that uses cyclophosphamide (chemotherapy), rabbit antithymocyte globulin (rATG) (a protein that kills the immune cells that are thought to be causing your disease), rituximab (a biologic drug that targets B cells of your immune system), and intravenous immunoglobulin (IVIg) (pooled IgG antibodies from plasma donors with immunomodulatory and anti-inflammatory effects), followed by return of your own previously collected blood stem cells (autologous stem cell transplant). One day of plasmapheresis will also be performed the day prior to admission for stem cell transplant to remove disease-causing antibodies. The ability of this experimental treatment to stop relapses and progression (worsening) of your NMOSD will be assessed.
- Conditions
- Neuromyelitis Optica, Devic's Disease, NMO Spectrum Disorder
- Being tested
- Rituximab, Cyclophosphamide, Mesna, rATG, Methylprednisolone
- Keywords
- Autologous Stem Cell Transplantation, Hematopoietic Stem Cell Transplant
- Medical subject headings
- Neuromyelitis Optica
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Rituxan
Monoclonal antibody therapy used to treat certain autoimmune diseases and types of cancer
CyclophosphamideDrug
Also called Cytoxan
A medication used as chemotherapy and to suppress the immune system
MesnaDrug
Also called Mesnex
A medication used in those taking cyclophosphamide or ifosfamide to decrease the risk of bleeding from the bladder
rATGDrug
Also called Thymoglobulin, Anti-Thymocyte Globulin
A rabbit polyclonal antibody to lymphocytes
Also called Solu-Medrol, Depo-Medrol
A corticosteroid medication used to suppress the immune system and decrease inflammation
G-CSFDrug
Also called Neupogen, Filgrastim, Granix, Zarxio
A glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream
IVIgBiological
Also called Bivigam, Carimune Nanofiltered (NF), Gammagard, Privigen
Pooled immunoglobulin (IgG) from thousands of plasma donors that has immunomodulatory and anti-inflammatory effects
Autologous Stem CellsBiological
Infusion of patient's own stem cells
| Study group | Role | What they receive |
|---|---|---|
| Hematopoietic Stem Cell Transplantation | Experimental | Hematopoietic Stem Cell Therapy will be performed as follows: Autologous stem cells will be infused after conditioning with rituximab, cyclophosphamide, mesna, rATG (rabbit), and methylprednisolone. Granulocyte-colony stimulating factor (G-CSF) and intravenous immunoglobulin (IVIg) will be administered post-transplant. Receives: Drug: Rituximab; 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.
Progression-Free Survival
Disease progression defined as: 1.0-point increase in the Expanded Disability Status Scale (EDSS) on consecutive evaluations at least six months apart and not due to a non-NMO disease process. The EDSS scale ranges from 0 to 10 in 0.5 increments that represent higher levels of disability.
Measured: 5 years
Secondary outcomes (9)
Relapse-Free Survival
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, drugs or related pseudo-exacerbation. Supportive confirmation by enhancement on MRI is preferred but not mandatory.
Measured: 5 years
Expanded Disability Status Scale (EDSS) Improvement
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
Measured: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Scripps Neurological Rating Scale (NRS) Improvement
The NRS scale ranges from 0 to 100 in 1 point increments that represent lower levels of disability.
Measured: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Improvement in Quality of Life
Measured using the short form (SF)-36 health survey.
Measured: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Paced Auditory Serial Addition Test (PASAT) Improvement
The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Improvement measured with the 2" and 3" versions
Measured: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Ambulation Index Improvement
The subject's walk of 25 feet is timed and a score from 0 to 10 is assigned based on their walk/gait and/or assistance required.
Measured: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
9 Hole Peg Test (9-HPT) Improvement
The 9-HPT is a brief, standardized, quantitative test of upper extremity function. Both the dominant and non-dominant hands are tested twice, with the total time to complete the task each time recorded and then averaged.
Measured: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Change in NMO IgG (aquaporin-4) Antibody Titer
Evaluation of the antibody titer, looking for a change from positive to negative.
Measured: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Improvement in Visual Acuity
A visual acuity test is an eye exam that checks how well one sees the details of a letter or symbol from a specific distance.
Measured: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2019
- Study startNov 2019 (estimated)
- Primary completionJan 2025 (estimated)
- Study completion28 Nov 2025 (estimated)
Why it stopped: Discontinued by Investigator
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuromyelitis OpticaStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 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
- NCT03829566
- Sponsor's protocol ID
- DIAD.ATTEND.2018
- Acronym
- ATTEND
- Status last verified
- Nov 2019
- First submitted
- 1 Feb 2019
- Last updated
- 20 Nov 2019
- Results posted
- No
- 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 20 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autologous Hematopoietic Stem Cell Transplant for Neuromyelitis Optica Spectrum Disorder (NMOSD)
- ClinicalTrials.gov ID
- NCT03829566
- Acronym / sponsor ID
- ATTEND / DIAD.ATTEND.2018
- Conditions
- Neuromyelitis Optica, Devic's Disease, NMO Spectrum Disorder
- Keywords
- Autologous Stem Cell Transplantation, Hematopoietic Stem Cell Transplant
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Discontinued by Investigator
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- Nov 2019 (estimated)
- Primary completion
- Jan 2025 (estimated)
- Study completion
- 28 Nov 2025 (estimated)
- First posted
- 4 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to treat your disease with an autologous stem cell transplant using a regimen of immune suppressant drugs and chemotherapy to reset your immune system and to determine if your disease will go into long-term remission.
Detailed description
The autologous stem cell transplant used in this research study is an investigational procedure that uses cyclophosphamide (chemotherapy), rabbit antithymocyte globulin (rATG) (a protein that kills the immune cells that are thought to be causing your disease), rituximab (a biologic drug that targets B cells of your immune system), and intravenous immunoglobulin (IVIg) (pooled IgG antibodies from plasma donors with immunomodulatory and anti-inflammatory effects), followed by return of your own previously collected blood stem cells (autologous stem cell transplant). One day of plasmapheresis will also be performed the day prior to admission for stem cell transplant to remove disease-causing antibodies. The ability of this experimental treatment to stop relapses and progression (worsening) of your NMOSD will be assessed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hematopoietic Stem Cell Transplantation | Experimental | Drug: Rituximab, 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 rituximab, cyclophosphamide, mesna, rATG (rabbit), and methylprednisolone. Granulocyte-colony stimulating factor (G-CSF) and intravenous immunoglobulin (IVIg) will be administered post-transplant. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age 18 - 65 years old at the time of pre-transplant evaluation
- An established diagnosis of NMOSD (with or without aquaporin 4 (AQP4)-IgG antibody)
Key exclusion criteria (30 listed)
- Under age of 18 or over age of 65
- Prisoners
- Psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible, or any adult who is unable to consent (for adults cognitively impaired due to disease, consent may be obtained from the closest living relative).
- Paraplegia or quadriplegia (must be able to use a walker if even for only a few feet)
- Extensive subcortical white matter lesions
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 |
|---|---|---|
| RituximabAlso: RituxanMonoclonal antibody therapy used to treat certain autoimmune diseases and types of cancer | Drug | Hematopoietic Stem Cell Transplantation |
| CyclophosphamideAlso: CytoxanA medication used as chemotherapy and to suppress the immune system | Drug | Hematopoietic Stem Cell Transplantation |
| MesnaAlso: MesnexA medication used in those taking cyclophosphamide or ifosfamide to decrease the risk of bleeding from the bladder | Drug | Hematopoietic Stem Cell Transplantation |
| rATGAlso: Thymoglobulin, Anti-Thymocyte GlobulinA rabbit polyclonal antibody to lymphocytes | Drug | Hematopoietic Stem Cell Transplantation |
| MethylprednisoloneAlso: Solu-Medrol, Depo-MedrolA corticosteroid medication used to suppress the immune system and decrease inflammation | Drug | Hematopoietic Stem Cell Transplantation |
| G-CSFAlso: Neupogen, Filgrastim, Granix, ZarxioA glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream | Drug | Hematopoietic Stem Cell Transplantation |
| IVIgAlso: Bivigam, Carimune Nanofiltered (NF), Gammagard, PrivigenPooled immunoglobulin (IgG) from thousands of plasma donors that has immunomodulatory and anti-inflammatory effects | Biological | Hematopoietic Stem Cell Transplantation |
| Autologous Stem CellsInfusion of patient's own stem cells | Biological | Hematopoietic Stem Cell Transplantation |
Primary outcome
Progression-Free Survival
Time frame: 5 years
Disease progression defined as: 1.0-point increase in the Expanded Disability Status Scale (EDSS) on consecutive evaluations at least six months apart and not due to a non-NMO disease process. The EDSS scale ranges from 0 to 10 in 0.5 increments that represent higher levels of disability.
9 secondary outcomes
Relapse-Free Survival
Time frame: 5 years
Expanded Disability Status Scale (EDSS) Improvement
Time frame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Scripps Neurological Rating Scale (NRS) Improvement
Time frame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Improvement in Quality of Life
Time frame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Paced Auditory Serial Addition Test (PASAT) Improvement
Time frame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Ambulation Index Improvement
Time frame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
9 Hole Peg Test (9-HPT) Improvement
Time frame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Change in NMO IgG (aquaporin-4) Antibody Titer
Time frame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Improvement in Visual Acuity
Time frame: 6 months, 1 year, 2 years, 3 years, 4 years, 5 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2019.
- 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
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Rituximab, Cyclophosphamide and Mesna in people with Neuromyelitis Optica and Devic's Disease, run by Northwestern University at 2 sites 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 2 inclusion and 30 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: withdrawn, as of the sponsor's last update on 20 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Progression-Free Survival (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 20 Nov 2019.