Multiple Sclerosis, Relapsing-RemittingNCT05482542
Optimal Conditioning Regimen for Autologous Transplantation of Relapsing Remitting Multiple Sclerosis
A study testing Autologous hematopoietic stem cell transplantation, Cyclophosphamide/ATG and Cyclophosphamide/Rituximab in people with Multiple Sclerosis, Relapsing-Remitting, run by Scripps Health at 1 site in United States.
Trial summary
This study is designed to compare two non-myeloablative conditioning regimens (combination of chemotherapy and immune specific proteins against immune cells) for relapsing remitting multiple sclerosis (RRMS). 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?
- Autologous hematopoietic stem cell transplantation, Cyclophosphamide/ATG and Cyclophosphamide/Rituximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2023to 1 Jul 2027
- Phase
- Interventional
- 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 58 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age 18-58 years old
- MRI T2 hyperintense lesions with at least 1 lesion in two or more of the following locations: periventricular, cortical or juxtacortical, infratentorial, or 1 spinal lesion
- Since diagnosis a new MRI T2 lesion or since diagnosis a gadolinium positive lesion and at least one T2 weighted lesion
- RRMS with a history of:
- 2 or more "active flares" in the prior 12 months despite either copaxone or interferon; or
- 1 or more "active flares" in the prior year despite a 2nd or 3rd generation DMT; or
- Active secondary progressive MS (aSPMS) with 2 or more gadolinium enhancing lesions with at least 1 gadolinium enhancing lesion > 5 mm in longest dimension within the last 9 months
Who cannot join
- CIS- clinically isolated lesion
- isolated optic neuritis
- Primary progressive MS b) Nonactive SPSM (defined as no new or enhancing lesions in last 12 months)
- spasticity or clinical stiffness of leg(s) unless there is documented new MRI enhancement within the past 12 months.
- hyperreflexia or clonus
- other immune neurologic disease such as NMO, CIDP, Stiff person syndrome, myasthenia gravis
Show all 51Show fewer
- genetic neurologic diseases such as CMT or spinal cerebellar degeneration
- another autoimmune diagnosis such as systemic lupus erythematosus, systemic sclerosis, Behcets, or crohn's disease, etc (with the exception of hypo or hyperthyroidism or history of ITP or AIHA that is in remission)
- insulin dependent diabetes mellitus
- sickle cell disease
- thalassemia major
- porphyria
- a current or prior cancer / malignancy except for cutaneous basal cell carcinoma or carcinoma in situ (completely excised)
- Hepatic:
- Liver function test (AST or ALT) > 2 x upper limit of normal or
- bilirubin > 2.0 mg /dl
- Pulmonary:
- DLCO < 60% of normal or;
- Asthma not easily corrected with bronchodilator therapy or;
- Pulmonary artery hypertension (pulmonary artery systolic pressure (PASP) > 40 mmHg on echocardiogram or by cardiac catheterization a mean pulmonary artery pressure (mPAP) > 25 mmHg; a cardiac catheterization for pulmonary artery pressures is only performed if clinically indicated)
- Renal:
- creatinine > 2.0 mg/dl, or
- nephrotic syndrome
- Cardiac:
- Acute myocardial infarction (AMI) within the last year, and if history of AMI not being approved by cardiology as low risk or not at increased risk for another AMI: or
- Persistent arrythmia not controlled with medication;
- Any patient requiring medication for an arrhythmia must be pre-approved by cardiology, or
- left ventricular ejection fraction < 45%
- Hematology
- Hereditary coagulopathy or currently receiving anticoagulation therapy
- platelets < 100,000
- myelodysplastic syndrome
- Infection:
- HIV,
- hepatitis B
- hepatitis C
- positive quantiferon gold (tuberculosis test) (may start HSCt once seen by ID and started on anti-tuberculous therapy, that will be continued throughout transplant, if asymptomatic),
- active infection at time of hospital admission (except UTI)
- EDSS < 2.0 at time of enrollment or insurance submission
- Inability to comprehend or give or sign informed consent
- Pregnancy (positive serum or urine HCG test) or breast feeding
- Failure to comprehend infertility as a complication.
- Failure to offer sperm or oocyte collection and storage
- Before HSCT failure to be Free of alemtuzumab for 12 months
- Before HSCT failure to be Free of natalizumab for 5 months
- Before HSCT failure to be Free of rituximab or ocrelizumab for 5 months
- Before HSCT failure to be Free of fingolimod for 3 months
- Before HSCT failure to be Free of dimethyl fumarate (tecfidera) for 3 months
- Before HSCT failure of teriflunomide to have plasma levels < 0.02 mg/L after either oral cholestyramine or activated charcoal clearance.
- Prior mitoxantrone
- Prior cladribine
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Optimal Conditioning Regimen Protocol for Autologous Hematopoietic Stem Cell Transplantation of Relapsing Remitting Multiple Sclerosis
This study is designed to compare two non-myeloablative conditioning regimens (combination of chemotherapy and immune specific proteins against immune cells) for relapsing remitting multiple sclerosis (RRMS). The two conditioning regimens are the most commonly used world wide in clinical practice for the treatment of multiple sclerosis (MS). The first investigational conditioning regimen is cyclophosphamide (chemotherapy) and rATG (rabbit anti-thymocyte globulin, a protein against immune cells). The second investigational conditioning regimen includes the same dose of cyclophosphamide (chemotherapy) and rituximab (a protein against immune cells). Both cyclophosphamide and either rATG or rituximab are given to kill immune cells that are thought to be causing MS, followed by return of one's own previously collected blood stem cells (autologous stem cell transplant) to hasten recovery. The goal of this study is to assess the difference of these treatments in terms of toxicity and efficacy.
Read the detailed description
Autologous hematopoietic stem cell transplantation (HSCT) in patients with active relapsing remitting multiple sclerosis (RRMS) halts disease progression, improves neurologic disability and quality of life, and provides a prolonged drug-free remission. A "position paper" by neurologists and hematologists under the American Society of Transplant and Cellular Therapy (ASTCT) has recommended autologous HSCT as standard of care, clinical evidence available, for treatment-refractory relapsing MS with high risk of future disability. Similarly, the EBMT has recommended the use of HSCT as "standard or care" for patients with highly active RRMS failing at least one DMT. Currently, the optimal conditioning regimen in terms of safety and efficacy is unknown. Herein, we will compare the two most commonly used regimens cyclophosphamide/ATG, or cyclophosphamide/rituximab in terms of safety and efficacy.
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Being tested
- Autologous hematopoietic stem cell transplantation, Cyclophosphamide/ATG, Cyclophosphamide/Rituximab
- Keywords
- Autologous Hematopoietic Stem Cell Transplant
- 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.
Autologous hematopoietic stem cell transplantationOther
Autologous hematopoietic stem cell transplantation
Cyclophosphamide/ATGDrug
Cyclophosphamide/ATG
Cyclophosphamide/RituximabDrug
Cyclophosphamide/Rituximab
| Study group | Role | What they receive |
|---|---|---|
| Cyclophosphamide/ATG Conditioning Regimen | Other | Cyclophosphamide (200 mg /kg) / rabbit antithymocyte globulin (6.0 mg/kg) Receives: Other: Autologous hematopoietic stem cell transplantation; Drug: Cyclophosphamide/ATG |
| Cyclophosphamide/Rituximab Conditioning Regimen | Other | Cyclophosphamide (200 mg/kg) / rituximab (1000 mg). Receives: Other: Autologous hematopoietic stem cell transplantation; Drug: Cyclophosphamide/Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Durability of remission between two arms
Defined as the time to first confirmed acute relapse or 5 years after treatment which ever comes first
Measured: Time to first confirmed acute relapse or 5 years after treatment which ever comes first
Secondary outcomes (1)
Neurologic Disability
Defined by change in EDSS (Expanded Disability Status Scale, ranges from 0 to 10 with 0 normal and 10 worst)
Measured: From initiation of study to completion, up until 5 years after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2022
- Study start1 Jan 2023
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Jul 2027 (estimated)
Why it stopped: lack of funding for support staff
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Scripps Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David J Hermel, MD, Principal investigator, Scripps Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05482542
- Sponsor's protocol ID
- IRB-21-7874
- Status last verified
- Dec 2022
- First submitted
- 12 Jul 2022
- Last updated
- 9 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimal Conditioning Regimen Protocol for Autologous Hematopoietic Stem Cell Transplantation of Relapsing Remitting Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT05482542
- Acronym / sponsor ID
- IRB-21-7874
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Keywords
- Autologous Hematopoietic Stem Cell Transplant
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: lack of funding for support staff
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Scripps HealthUniversity, hospital or other
- Study start
- 1 Jan 2023 (actual)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 1 Jul 2027 (estimated)
- First posted
- 1 Aug 2022 (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 compare two non-myeloablative conditioning regimens (combination of chemotherapy and immune specific proteins against immune cells) for relapsing remitting multiple sclerosis (RRMS). The two conditioning regimens are the most commonly used world wide in clinical practice for the treatment of multiple sclerosis (MS). The first investigational conditioning regimen is cyclophosphamide (chemotherapy) and rATG (rabbit anti-thymocyte globulin, a protein against immune cells). The second investigational conditioning regimen includes the same dose of cyclophosphamide (chemotherapy) and rituximab (a protein against immune cells). Both cyclophosphamide and either rATG or rituximab are given to kill immune cells that are thought to be causing MS, followed by return of one's own previously collected blood stem cells (autologous stem cell transplant) to hasten recovery. The goal of this study is to assess the difference of these treatments in terms of toxicity and efficacy.
Detailed description
Autologous hematopoietic stem cell transplantation (HSCT) in patients with active relapsing remitting multiple sclerosis (RRMS) halts disease progression, improves neurologic disability and quality of life, and provides a prolonged drug-free remission. A "position paper" by neurologists and hematologists under the American Society of Transplant and Cellular Therapy (ASTCT) has recommended autologous HSCT as standard of care, clinical evidence available, for treatment-refractory relapsing MS with high risk of future disability. Similarly, the EBMT has recommended the use of HSCT as "standard or care" for patients with highly active RRMS failing at least one DMT. Currently, the optimal conditioning regimen in terms of safety and efficacy is unknown. Herein, we will compare the two most commonly used regimens cyclophosphamide/ATG, or cyclophosphamide/rituximab in terms of safety and efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cyclophosphamide/ATG Conditioning Regimen | Other | Other: Autologous hematopoietic stem cell transplantation, Drug: Cyclophosphamide/ATGCyclophosphamide (200 mg /kg) / rabbit antithymocyte globulin (6.0 mg/kg) |
| Cyclophosphamide/Rituximab Conditioning Regimen | Other | Other: Autologous hematopoietic stem cell transplantation, Drug: Cyclophosphamide/RituximabCyclophosphamide (200 mg/kg) / rituximab (1000 mg). |
Who may qualify
- Ages
- 18 to 58 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Age 18-58 years old
- MRI T2 hyperintense lesions with at least 1 lesion in two or more of the following locations: periventricular, cortical or juxtacortical, infratentorial, or 1 spinal lesion
- Since diagnosis a new MRI T2 lesion or since diagnosis a gadolinium positive lesion and at least one T2 weighted lesion
- RRMS with a history of:
Key exclusion criteria (51 listed)
- CIS- clinically isolated lesion
- isolated optic neuritis
- Primary progressive MS b) Nonactive SPSM (defined as no new or enhancing lesions in last 12 months)
- spasticity or clinical stiffness of leg(s) unless there is documented new MRI enhancement within the past 12 months.
- hyperreflexia or clonus
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 |
|---|---|---|
| Autologous hematopoietic stem cell transplantationAutologous hematopoietic stem cell transplantation | Other | Cyclophosphamide/ATG Conditioning Regimen, Cyclophosphamide/Rituximab Conditioning Regimen |
| Cyclophosphamide/ATGCyclophosphamide/ATG | Drug | Cyclophosphamide/ATG Conditioning Regimen |
| Cyclophosphamide/RituximabCyclophosphamide/Rituximab | Drug | Cyclophosphamide/Rituximab Conditioning Regimen |
Primary outcome
Durability of remission between two arms
Time frame: Time to first confirmed acute relapse or 5 years after treatment which ever comes first
Defined as the time to first confirmed acute relapse or 5 years after treatment which ever comes first
1 secondary outcome
Neurologic Disability
Time frame: From initiation of study to completion, up until 5 years after treatment
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 9 Nov 2023.
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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.
David J Hermel, MD principal investigator
Scripps Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Autologous hematopoietic stem cell transplantation, Cyclophosphamide/ATG and Cyclophosphamide/Rituximab in people with Multiple Sclerosis, Relapsing-Remitting, run by Scripps Health 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 7 inclusion and 51 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 9 Nov 2023. 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.
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?
Durability of remission between two arms (time frame: Time to first confirmed acute relapse or 5 years after treatment which ever comes first). 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 9 Nov 2023.