Addition of Cord Blood Tissue-Derived Mesenchymal Stromal Cells to Ruxolitinib for the Treatment of Steroid-Refractory Acute Graft Versus Host Disease

Официальное название

A Randomized Controlled Pilot Study of Two Doses of Cord Blood Tissue-Derived Mesenchymal Stromal Cells Combined With Ruxolitinib Versus Ruxolitinib Alone for Therapy of Steroid-Refractory Acute Graft Versus Host Disease

Обзор

This early phase I trial is to find out the effect of adding cord blood tissue-derived mesenchymal stromal cells (cb-MSCs) to ruxolitinib in treating patients with acute graft versus host disease that does not respond to steroid therapy (steroid-refractory). Ruxolitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. cb-MSCs are a type of tissue helper cell that can be removed from donated umbilical cord blood tissue and grown into many different cell types that can be used to treat cancer and other disease, such as graft versus host disease. This trial aims to learn if adding cb-MSCs to ruxolitinib may help control steroid-refractory acute graft versus host disease.

Подробное описание

PRIMARY OBJECTIVE:

I. To estimate between-arm differences (Arm 3 versus \[vs\] Arm 1, and Arm 2 vs Arm 1) for each of the 28-day co-primary outcome probabilities.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM 1: Patients receive ruxolitinib orally (PO) twice daily (BID) for at least 3 days and may consider tapering after 6 months of therapy if response occurs and therapeutic corticosteroid doses have been discontinued.

ARM 2: Patients receive ruxolitinib PO BID as in Arm 1. Patients also receive lower dose of cb-MSCs intravenously (IV) for up to 60 minutes twice weekly (at least 3 days apart) over 4 consecutive weeks for 8 total doses.

ARM 3: Patients receive ruxolitinib PO BID as in Arm 1. Patients also receive higher dose of cb-MSCs IV for up to 60 minutes twice weekly (at least 3 days apart) over 4 consecutive weeks for 8 total doses.

After completion of study treatment, patients are followed up on day 28 and then for up to 6 months.

Вмешательства

• Другое Cellular Therapy
  Given ds-MSCs IV
• Препарат Ruxolitinib
  Given PO

Первичные конечные точки

• Death from any cause [Срок оценки: Within 28 days from the start of active study treatment]
• Response [Срок оценки: At day 28 from start of therapy on study]
• Incidence of adverse events [Срок оценки: Within 28 days from the start of active study treatment]

Вторичные конечные точки (12)

• Graft versus host disease status [Срок оценки: At days 7, 14, 21 and 28 post treatment]
• Proportion of response [Срок оценки: At days 7, 14, 21 and 28 post treatment]
• Time to complete response [Срок оценки: Up to 6 months]
• Time to very good partial response [Срок оценки: Up to 6 months]
• Time to partial response [Срок оценки: Up to 6 months]
• Incidence of complete response for each organ [Срок оценки: Up to 6 months]
• Incidence of very good partial response for each organ [Срок оценки: Up to 6 months]
• Incidence of partial response for each organ [Срок оценки: Up to 6 months]
• Durability of organ response [Срок оценки: Up to 6 months]
• Cumulative incidence of non-relapse mortality (NRM) [Срок оценки: At 6 months post treatment]
• Cumulative incidence of relapse/progression of the primary disease [Срок оценки: At 6 months]
• Overall survival [Срок оценки: From enrollment to death from any cause, assessed at 6 months]

Критерии участия

Критерии включения

• Participants between the ages of 12 years and 80 years (inclusive).
• Steroid refractory grades II-IV acute GVHD of the Lower GI tract or Liver (including those developing these manifestations after previous acute GVHD of skin) secondary to allogeneic HCT or donor lymphocyte infusion. (Grading, see Appendix I) GVHD with: No improvement after treatment with methylprednisolone at ≥ 2.0 mg/kg/day or equivalent for minimum 7 days, or progressive symptoms after minimum 3 days, or a flare in acute GVHD while on systemic steroids. Participants must have had a biopsy that suggests GVHD; a repeat biopsy to enroll on the study is not necessary.
• Karnofsky/Lansky Performance score of at least 30 at the time of study entry.
• Participants who are women of childbearing potential, must be non-pregnant, not breast-feeding, and use adequate contraception. Male patients must use adequate contraception
• Participants (or legal representative where appropriate) must be capable of providing written informed consent, and assent if indicated.

Критерии исключения

• De novo chronic GVHD
• Isolated acute GVHD of skin
• Secondary systemic therapy for acute GVHD ruxolitinib greater than 96 hours before initiation of therapy.
• Primary treatment with agents other than alpha-1 antitrypsin (AAT) glucocorticoids and ruxolitinib.
• Participants with uncontrolled infections will be excluded. Infections are considered controlled if appropriate therapy has been instituted and, at the time of enrollment, no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
• Adult and pediatric patients with cognitive impairments and/or any serious unstable pre-existing medical condition or psychiatric disorder that can interfere with safety or with obtaining informed consent or compliance with study procedures.
• Participants with significant supplemental oxygen requirement defined as >6 L oxygen by nasal cannula.
• Participants with known allergy to bovine or porcine products.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• M D Anderson Cancer Center — Houston

Идентификаторы

NCT: NCT04744116 · 2019-1122 · NCI-2020-13889 · 2019-1122 · P01CA148600

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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