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

Phase 1

Not yet recruiting

• Conditions: Primary Progressive Multiple Sclerosis; Multiple Sclerosis; Multiple Sclerosis, Primary Progressive; Multiple Sclerosis, Secondary Progressive
• Interventions: Biological: Orca-Q; Drug: myeloablative regimen

• Registration Number: NCT06900192
• Lead Sponsor: Stanford University

Brief Summary

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 Timeline

• Study First Submitted: 2025-02-03
• Status Verified: 2025-03
• Study Start: 2025-03
• Study First Submitted QC: 2025-03-26
• Last Update Submitted: 2025-03-26
• Study First Posted: 2025-03-28
• Last Update Posted: 2025-03-28
• Primary Completion: 2029-08
• Study Completion: 2029-08

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

Not provided

Exclusion Criteria

1. History of Progressive Multifocal Leukoencephalopathy

2. Organ dysfunction or disease that would jeopardize survival after hematopoietic cell transplantation, including but not limited to the following:

   1. Renal insufficiency as defined by an estimated GFR <60 mL/minute
   2. 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)
   3. 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.
   4. Necroinflammatory or fibrotic liver disease with evidence of liver dysfunction, including but not limited to jaundice, hepatic encephalopathy, or portal hypertension
   5. 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.
   6. Poorly controlled hypertension despite appropriate therapy, defined as a diastolic blood pressure greater than 90 mm Hg while on therapy.
   7. Poorly controlled diabetes mellitus, defined as HgbA1c ≥ 6.5% despite therapy or recurrent hypoglycemia while on therapy.
   8. 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.)

3. History of smoking either tobacco or other herbal products in the last 3 months.

4. 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.

5. HIV seropositive.

6. 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.

7. HCV seropositive, unless PCR negative and having undergone 'curative' antiviral therapy.

8. Participant has active uncontrolled infection

9. Participant has demonstrated lack of compliance with prior medical care

10. 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.

11. Participants whose life expectancy is severely limited by illness other than multiple sclerosis

12. Females who are pregnant or breast feeding.

13. Medical or psychiatric conditions that compromise ability to give informed consent or to comply with treatment protocol

14. Inability to undergo an MRI scan

15. Currently receiving treatment with investigational agents

16. Positive for JC virus DNA in the CSF or blood during screening.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Orca-Q Graft with lymphodepleting conditioning regimen	Orca-Q	Donor Orca-Q stem cell graft
Orca-Q Graft with lymphodepleting conditioning regimen	myeloablative regimen	Donor Orca-Q stem cell graft

Primary Outcome Measures

Name	Time	Method
Severe acute Graft-versus-Host-Disease-free survival	365 days after infusion	Alive without a history of moderate to severe aGVHD

Secondary Outcome Measures

Name	Time	Method
Evaluate treatment response	Measurements will be taken at 9 and 12 months after infusion	Neurologically stable. Assessment of neurological function will be measured by employing the expanded disability status scale (EDSS)
Evaluate safety of treatment	Measured from time of enrollment to end of study participation (from date of consent to month 12).	Regimen-related toxicity, incidence and severity of GVHD, primary and secondary graft failure