Study of Efficacy and Safety of Ruxolitinib in Chinese Participants With Corticosteroid-refractory Chronic Graft vs. Host Disease

Официальное название

A Single-arm Multi-center Study of Ruxolitinib in Chinese Participants With Corticosteroid-refractory Chronic Graft Versus Host Disease After Allogeneic Stem Cell Transplantation

Обзор

The purpose of the study is to assess the efficacy and safety of ruxolitinib in Chinese adult and pediatric participants aged 12 years or older with corticosteroid-refractory chronic graft vs. host disease (SR-cGvHD).

Подробное описание

This is a single arm, multi-center, open label study which will enroll approximately 50 participants and investigate the efficacy and safety of ruxolitinib administered in adult and adolescent (≥12 years old) Chinese participants with SR-cGvHD.

The total duration on study for an individual participant will be up to 164 weeks (approximately 3 years).

The study consists of following periods, with each cycle comprised of 4 weeks (28 days):

* Screening Period (Day -28 to Day -1) * Treatment period (Day 1 to Cycle 39/EOT) * Safety follow-up (Last dose +30 days) * Long-term survival follow-up period (EOT to 156 weeks on study).

Вмешательства

• Препарат Ruxolitinib
  Ruxolitinib is taken orally daily at 10 mg BID, given as two 5 mg tablets.

Первичные конечные точки

• Overall Response Rate (ORR) [Срок оценки: Cycle 7 Day 1; each Cycle =28 days]

Вторичные конечные точки (8)

• Failure-free Survival (FFS) [Срок оценки: up to 3 years]
• Best Overall Response (BOR) [Срок оценки: at any point up to cycle 7 day 1 (each cycle is 28 days) or the start of additional systemic therapy for cGvHD, approx. 6 months]
• ORR at end of cycle 3 [Срок оценки: end of cycle 3; each cycle = 28 days]
• Duration of Response (DOR) [Срок оценки: from first response until cGvHD progression, death, or the date of addition of systemic therapies for cGvHD, approx.36 months]
• Overall Response (OS) [Срок оценки: from the date of study treatment (ruxolitinib) initiation to the date of death due to any cause, approx. 36 months]
• Non-Relapse Mortality (NRM) [Срок оценки: from date of study treatment (ruxolitinib) initiation to date of death not preceded by underlying disease relapse/recurrence, approx. 36 months]
• Malignancy Relapse/Recurrence (MR) [Срок оценки: from date of study treatment to hematologic malignancy relapse/recurrence, approx. 36 months]
• Reduction of daily corticosteroids dose at cycle 7 day 1 [Срок оценки: Cycle 7 Day 1; each cycle = 28 days]

Критерии участия

Критерии включения

• Signed informed consent must be obtained prior to participation in the study.
• Male or female Chinese participants aged 12 or older at the time of informed consent
• Able to swallow tablets.- Have undergone alloSCT from any donor source (matched unrelated donor, sibling, haplo-identical) using bone marrow, peripheral blood stem cells, or cord blood. Recipients of non-myeloablative, myeloablative, and reduced intensity conditioning are eligible.
• Evident myeloid and platelet engraftment:

• Absolute neutrophil count (ANC) >1,000/mm3 AND
• Platelet count ≥25,000/mm3

Note: Use of growth factor supplementation and transfusion support is allowed during the trial, however, transfusion to reach a minimum platelet count for inclusion is not allowed during screening and at baseline.

• Participants with clinically diagnosed cGvHD staging of moderate to severe according to NIH Consensus Criteria (Jagasia et al 2015) prior to Cycle 1 Day 1.

• Moderate cGvHD: at least one organ (not lung) with a score of 2, 3 or more organs involved with a score of 1 in each organ, or lung score of 1.
• Severe cGvHD: at least 1 organ with a score of 3, or lung score of 2 or 3.
• Participants currently receiving systemic corticosteroids for the treatment of cGvHD for a duration of < 12 months prior to Cycle 1 Day 1, and have a confirmed diagnosis of corticosteroid refractory cGvHD defined per 2014 NIH consensus criteria (Martin et al 2015) irrespective of the concomitant use of a calcineurin inhibitor, as follows:

• A lack of response or disease progression after administration of minimum prednisone 1 mg/kg/day for at least 1 week (or equivalent) OR
• Disease persistence without improvement despite continued treatment with prednisone at >0.5 mg/kg/day or 1 mg/kg/every other day for at least 4 weeks (or equivalent) OR
• Increase to prednisone dose to >0.25 mg/kg/day after two unsuccessful attempts to taper the dose (or equivalent)
• Participants has Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Критерии исключения

For a full list of exclusion criteria, refer to Section 5.2. Key exclusion criteria include

• Participants who have received two or more systemic treatments for cGvHD in addition to corticosteroids ± CNI for cGvHD.
• Participants who have received ROCK2 inhibitors for cGvHD.
• Participants that transition from active aGvHD to cGvHD without tapering off corticosteroids ± CNI and any systemic treatment

Note: Participants receiving up to 30 mg by mouth once a day of hydrocortisone (i.e., physiologic replacement dose) of corticosteroids are allowed.

• Participants who were treated with prior JAK inhibitors for aGvHD; except when the participant achieved complete or partial response and has been off JAK inhibitor treatment for at least 8 weeks prior to Cycle 1 Day 1.
• Failed prior alloSCT within the past 6 months from Cycle 1 Day 1.
• Participants with relapsed primary malignancy, or who have been treated for relapse after the alloSCT was performed.
• SR-cGvHD occurring after a non-scheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. Participants who have received a scheduled DLI as part of their transplant procedure and not for management of malignancy relapse are eligible.

Other protocol-defined inclusion/exclusion may apply.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 22 центра

• Novartis Investigative Site — Хэфэй
• Novartis Investigative Site — Гуанчжоу
• Novartis Investigative Site — Гуанчжоу
• Novartis Investigative Site — Nanning
• Novartis Investigative Site — Guiyang
• Novartis Investigative Site — Shijiazhuang
• Novartis Investigative Site — Чжэнчжоу
• Novartis Investigative Site — Ухань
• … и ещё 14 центров

Идентификаторы

NCT: NCT06824103 · CINC424D2413

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗