Primary Progressive Multiple SclerosisPhase 1NCT06900192
A Study of Allogeneic Hematopoietic Cell Transplantation for Primary Progressive Multiple Sclerosis
A Phase 1 study testing Orca-Q and myeloablative regimen in people with Primary Progressive Multiple Sclerosis and Multiple Sclerosis, run by Stanford University.
Trial summary
A study of alloHCT with Orca-Q for the treatment of primary progressive multiple sclerosis (MS). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Primary Progressive Multiple Sclerosis, Multiple Sclerosis, Multiple Sclerosis, Primary Progressive
- What is being tested?
- Orca-Q and myeloablative regimen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- No sites listed yet
- Study dates
- Mar 2025to Aug 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Participants aged ≥18 and ≤65 years with primary progressive multiple sclerosis
- A diagnosis of PPMS by 2017 McDonald criteria and 2013 clinical course revision102
- CSF with elevated IgG index or 2 or more oligoclonal bands
- EDSS (see Appendix 9) between 2.0 and 5.5 inclusive
- Based on review of the clinical records, there must be a deterioration in the EDSS of at least 1 or more points over the previous 4 years (or less).
- Eligibility criteria confirmed by the Eligibility Review Group (Appendix 10)
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- Recipients who have been treated with ocrelizumab, rituximab, ofatumumab, ublituximab, or alemtuzumab must undergo a washout period as described in Appendix 14 prior to their planned day 0.
- Recipients must be willing to undergo mobilized autologous peripheral blood stem cell collection to create a cryopreserved rescue product prior to alloHCT.
- Ability to undergo MRI without general anesthesia
- Ability to undergo all tests and procedures in the study
- Patients who are not vaccinated for COVID-19 must have no symptoms of COVID-19 and have negative testing for COVID-19. For other vaccine-preventable illnesses, it is recommended that patients are current on their vaccination schedule.
Who cannot join
- History of Progressive Multifocal Leukoencephalopathy
- Organ dysfunction or disease that would jeopardize survival after hematopoietic cell transplantation, including but not limited to the following:
- Renal insufficiency as defined by an estimated GFR <60 mL/minute
- Cardiac dysfunction as defined by symptomatic coronary artery disease, congestive heart failure, valvular heart disease, cardiomyopathy, uncontrolled arrhythmia(s), or left ventricular ejection fraction <50%. Participants with a history of these conditions may enroll if they are demonstrated to have optimal cardiac function (as defined by echocardiography or multi-gated acquisition scan)
- Pulmonary dysfunction that poses a risk of mortality after transplant, defined as pre-transplant pulmonary function testing demonstrating a FEV1 <70% expected and/or a DLCOadj <70% expected.
- Necroinflammatory or fibrotic liver disease with evidence of liver dysfunction, including but not limited to jaundice, hepatic encephalopathy, or portal hypertension
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- Marrow dysfunction that poses a risk of peri-transplant mortality, defined as an absolute neutrophil count (<1000/mm3) below the lower limit of normal, or a platelet count below 50,000/mm3.
- Poorly controlled hypertension despite appropriate therapy, defined as a diastolic blood pressure greater than 90 mm Hg while on therapy.
- Poorly controlled diabetes mellitus, defined as HgbA1c ≥ 6.5% despite therapy or recurrent hypoglycemia while on therapy.
- Extreme protein-calorie malnutrition defined by Body Mass Index <18 and unintentional weight loss (3 kg in the last month or 6 kg in the last 6 months.)
- History of smoking either tobacco or other herbal products in the last 3 months.
- Planned pharmaceutical in vivo or ex vivo T cell depletion (TCD), eg, cladribine, or peritransplant antithymocyte globulin (ATG). For participants who have previously been exposed to a TCD agent, a 5-half-life washout of the agent must occur prior to planned day 0 (day 0 is defined as the day of infusion Orca-Q Prime). The washout period for alemtuzumab is listed in Appendix 14.
- HIV seropositive.
- HBV serology results indicating chronic HBV infection per https://www.cdc.gov/hepatitis/hbv/interpretationOfHepBSerologicResults.htm, unless HBV PCR negative. HBV seropositive participants should be on antiviral therapy after transplant.
- HCV seropositive, unless PCR negative and having undergone 'curative' antiviral therapy.
- Participant has active uncontrolled infection
- Participant has demonstrated lack of compliance with prior medical care
- Participants with known active malignancy. It is recommended that patients are current on cancer screening tests for their age and family history as per the NCCN [The National Comprehensive Cancer Network®] Guidelines. Screening should be performed, if indicated, per NCCN guidelines prior to study treatment.
- Participants whose life expectancy is severely limited by illness other than multiple sclerosis
- Females who are pregnant or breast feeding.
- Medical or psychiatric conditions that compromise ability to give informed consent or to comply with treatment protocol
- Inability to undergo an MRI scan
- Currently receiving treatment with investigational agents
- Positive for JC virus DNA in the CSF or blood during screening.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
Multiple Sclerosis and Neuroimmunology Study Team contact
About this study
Official title: A Multicenter Phase 1 Study of Allogeneic Hematopoietic Cell Transplantation for Primary Progressive Multiple Sclerosis Using Orca-Q, an Engineered Donor Graft Derived From Mobilized Peripheral Blood
A study of alloHCT with Orca-Q for the treatment of primary progressive multiple sclerosis (MS).
Read the detailed description
This study will evaluate alloHCT with Orca-Q, an allogeneic hematopoietic graft isolated from a donor's hematopoietic cells for the treatment of primary progressive MS.
- Conditions
- Primary Progressive Multiple Sclerosis, Multiple Sclerosis, Multiple Sclerosis, Primary Progressive, Multiple Sclerosis, Secondary Progressive
- Being tested
- Orca-Q, myeloablative regimen
- Medical subject headings
- Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Orca-QBiological
Allogeneic (donor) stem cell graft
myeloablative regimenDrug
Also called busulfan, fludarabine, thiotepa
Myeloablative regimen of busulfan, fludarabine, and thiotepa.
| Study group | Role | What they receive |
|---|---|---|
| Orca-Q Graft with lymphodepleting conditioning regimen | Experimental | Donor Orca-Q stem cell graft Receives: Biological: Orca-Q; Drug: myeloablative regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Severe acute Graft-versus-Host-Disease-free survival
Alive without a history of moderate to severe aGVHD
Measured: 365 days after infusion
Secondary outcomes (2)
Evaluate treatment response
Neurologically stable. Assessment of neurological function will be measured by employing the expanded disability status scale (EDSS)
Measured: Measurements will be taken at 9 and 12 months after infusion
Evaluate safety of treatment
Regimen-related toxicity, incidence and severity of GVHD, primary and secondary graft failure
Measured: Measured from time of enrollment to end of study participation (from date of consent to month 12).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2025
- Study startMar 2025 (estimated)
- Primary completionAug 2029 (estimated)
- Study completionAug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Progressive Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Stanford 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Orca Biosystems, Inc.
- Responsible party
- Principal investigator, Everett Meyer, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06900192
- Sponsor's protocol ID
- 75412
- Status last verified
- Mar 2025
- First submitted
- 3 Feb 2025
- Last updated
- 28 Mar 2025
- 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 28 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase 1 Study of Allogeneic Hematopoietic Cell Transplantation for Primary Progressive Multiple Sclerosis Using Orca-Q, an Engineered Donor Graft Derived From Mobilized Peripheral Blood
- ClinicalTrials.gov ID
- NCT06900192
- Acronym / sponsor ID
- 75412
- Conditions
- Primary Progressive Multiple Sclerosis, Multiple Sclerosis, Multiple Sclerosis, Primary Progressive, Multiple Sclerosis, Secondary Progressive
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- Orca Biosystems, Inc.
- Study start
- Mar 2025 (estimated)
- Primary completion
- Aug 2029 (estimated)
- Study completion
- Aug 2029 (estimated)
- First posted
- 28 Mar 2025 (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.
A study of alloHCT with Orca-Q for the treatment of primary progressive multiple sclerosis (MS).
Detailed description
This study will evaluate alloHCT with Orca-Q, an allogeneic hematopoietic graft isolated from a donor's hematopoietic cells for the treatment of primary progressive MS.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Orca-Q Graft with lymphodepleting conditioning regimen | Experimental | Biological: Orca-Q, Drug: myeloablative regimenDonor Orca-Q stem cell graft |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Participants aged ≥18 and ≤65 years with primary progressive multiple sclerosis
- A diagnosis of PPMS by 2017 McDonald criteria and 2013 clinical course revision102
- CSF with elevated IgG index or 2 or more oligoclonal bands
- EDSS (see Appendix 9) between 2.0 and 5.5 inclusive
- Based on review of the clinical records, there must be a deterioration in the EDSS of at least 1 or more points over the previous 4 years (or less).
Key exclusion criteria (24 listed)
- History of Progressive Multifocal Leukoencephalopathy
- Organ dysfunction or disease that would jeopardize survival after hematopoietic cell transplantation, including but not limited to the following:
- History of smoking either tobacco or other herbal products in the last 3 months.
- Planned pharmaceutical in vivo or ex vivo T cell depletion (TCD), eg, cladribine, or peritransplant antithymocyte globulin (ATG). For participants who have previously been exposed to a TCD agent, a 5-half-life washout of the agent must occur prior to planned day 0 (day 0 is defined as the day of infusion Orca-Q Prime). The washout period for alemtuzumab is listed in Appendix 14.
- HIV seropositive.
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 |
|---|---|---|
| Orca-QAllogeneic (donor) stem cell graft | Biological | Orca-Q Graft with lymphodepleting conditioning regimen |
| myeloablative regimenAlso: busulfan, fludarabine, thiotepaMyeloablative regimen of busulfan, fludarabine, and thiotepa. | Drug | Orca-Q Graft with lymphodepleting conditioning regimen |
Primary outcome
Severe acute Graft-versus-Host-Disease-free survival
Time frame: 365 days after infusion
Alive without a history of moderate to severe aGVHD
2 secondary outcomes
Evaluate treatment response
Time frame: Measurements will be taken at 9 and 12 months after infusion
Evaluate safety of treatment
Time frame: Measured from time of enrollment to end of study participation (from date of consent to month 12).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2025.
- 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.
Multiple Sclerosis and Neuroimmunology Study Team contact
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Orca-Q and myeloablative regimen in people with Primary Progressive Multiple Sclerosis and Multiple Sclerosis, run by Stanford University.
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 11 inclusion and 24 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: opening soon, as of the sponsor's last update on 28 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Multiple Sclerosis and Neuroimmunology Study Team (650-319-5522, neuroimmunologyresearch@stanford.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Severe acute Graft-versus-Host-Disease-free survival (time frame: 365 days after infusion). 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 28 Mar 2025.