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

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

• Биопрепарат Orca-Q
  Allogeneic (donor) stem cell graft
• Препарат myeloablative regimen
  Myeloablative regimen of busulfan, fludarabine, and thiotepa.

Первичные конечные точки

• Severe acute Graft-versus-Host-Disease-free survival [Срок оценки: 365 days after infusion]

Вторичные конечные точки (2)

• Evaluate treatment response [Срок оценки: Measurements will be taken at 9 and 12 months after infusion]
• Evaluate safety of treatment [Срок оценки: Measured from time of enrollment to end of study participation (from date of consent to month 12).]

Критерии участия

Inclusion Criteria (Recipient):

• 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.

Критерии исключения

• 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.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06900192 · 75412

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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