A Study of Allogeneic Hematopoietic Cell Transplantation for Primary Progressive Multiple Sclerosis

NCT06900192 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 75412
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

A study of alloHCT with Orca-Q for the treatment of primary progressive multiple sclerosis (MS).

Conditions

Primary Progressive Multiple Sclerosis; Multiple Sclerosis; Multiple Sclerosis, Primary Progressive; Multiple Sclerosis, Secondary Progressive

Outcome Measures

Primary Outcomes (1)

• Severe acute Graft-versus-Host-Disease-free survival

  Alive without a history of moderate to severe aGVHD

  365 days after infusion

Secondary Outcomes (2)

• Evaluate treatment response

  Measurements will be taken at 9 and 12 months after infusion

• Evaluate safety of treatment

  Measured from time of enrollment to end of study participation (from date of consent to month 12).

Study Arms (1)

Orca-Q Graft with lymphodepleting conditioning regimen

EXPERIMENTAL

Donor Orca-Q stem cell graft

Biological: Orca-Q; Drug: myeloablative regimen

Interventions

Orca-Q BIOLOGICAL

Allogeneic (donor) stem cell graft

Orca-Q Graft with lymphodepleting conditioning regimen

myeloablative regimen DRUG

Myeloablative regimen of busulfan, fludarabine, and thiotepa.

Also known as: busulfan, fludarabine, thiotepa

Orca-Q Graft with lymphodepleting conditioning regimen

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Stanford University: lead
• Orca Biosystems, Inc.: collaborator

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis

Interventions

Busulfan; fludarabine; Thiotepa

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Multiple Sclerosis and Neuroimmunology Study Team

CONTACT

650-319-5522; neuroimmunologyresearch@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: February 3, 2025
• First Posted: March 28, 2025
• Study Start: March 1, 2025
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: March 28, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share