2025-521940-39-00招募中2 期
Phase 2 Trial to determine the efficacy of belumosudil for patients with steroid-refractory overlap of syndrome Graft-versus-Host-Disease (SR-osGVHD) - BEAT-GVHD
Medical Center - University Of Freiburg1 个研究点 分布在 1 个国家目标入组 24 人开始时间: 2025年12月5日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Assessment by ORR at the week 25 (Cycle 7 Day 1) visit. The ORR is defined as the proportion of patients demonstrating a CR or PR without the requirement of additional systemic therapies for an earlier progression, mixed response or non-response. Scoring of response will be relative to the organ score at the time of baseline assessment. Missing values will be counted as non-responders
研究概览
简要总结
Primary objective is to perform a first evaluation of the efficacy of belumosudil in patients with moderate to severe steroid refractory-overlap syndrome (os) graft-versus-host-disease (GVHD) assessed by Overall Response Rate (ORR) at week 25 (Cycle 7 Day 1).
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Primary efficacy period
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Male and female patients aged ≥18 years
- •Participant is willing and able to give informed consent for participation in the study
- •Patient body weight ≥40kg.
- •Patients 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.
- •Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines.
- •SR-osGVHD diagnosis: Patients with clinically diagnosed moderate to severe osGVHD according to NIH Consensus Criteria
- •Patients who have received systemic glucocorticoids for the treatment of chronic graft-versus-host disease for a duration of < 6 months prior to cycle 1 day 1 and have a confirmed diagnosis of steroid refractory osGVHD defined per 2014 NIH consensus criteria (Martin 2015) irrespective of the concomitant use of a CNI, as follows:•A lack of response or disease progression after administration of minimum prednisone 1 mg/kg/day for ≥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 ≥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)
- •Evident myeloid and platelet engraftment: absolute neutrophil count (ANC)>1x109/L and platelet count >20x109/L
- •Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of hCG) within 24 hours prior to the start of study drug.
- •Able to swallow tablets
- •Eastern Co-operative Oncology Group (ECOG) performance status 0, 1, or 2
排除标准
- •Patient has received more than one systemic treatment for cGVHD other than corticosteroids + calcineurin inhibitors (CNI) (prophylaxis or treatment).
- •Hepatic impairment with Child-Pugh B or C liver cirrhosis. AST or ALT 5x upper limit of normal (ULN) or higher or bilirubin 1.5x ULN or higher even if liver impairment is likely due to GVHD
- •Impairment of gastrointestinal (GI) function (unrelated to GVHD) or GI disease (unrelated to GVHD) that may significantly alter the absorption of oral belumosudil (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
- •Any corticosteroid therapy for indications other than cGVHD at doses >1 mg/kg/day methylprednisolone or equivalent within 7 days before Cycle 1 Day
- •Patient is receiving and does not agree to stop herbal preparations/medications. These herbal medications include, but are not limited to, St. John’s Wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Patients must stop using herbal medications at least 7 days prior to first dose of study treatment.
- •Known allergies, hypersensitivity, or intolerance of belumosudil or any of its excipients or similar compounds.
- •Sexually active men and female patients of child-bearing potential who are not willing to use highly effective methods of contraception during the trial and at least 1 week after the last belumosudil
- •Pregnancy and lactation
- •Failed prior allogeneic hematopoietic stem cell transplantation (alloSCT) within the past 6 months.
- •Presence of an active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, 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.
- •Evidence of active viral infection (confirmed by peripheral blood viral load) including CMV, EBV, HBV, or HCV. Patients with pre-transplant positive serology results indicative of high risk for viral reactivation must have negative viral load results within 28 days prior toCycle 1 Day
- •Patients whose immune status is unknown or uncertain (e.g. serologies not obtained prior to transplant) must have viral load results confirming no evidence of active viral infection within 28 days prior toCycle 1 day
- •Presence of relapsed primary malignancy, or who have been treated for relapse after the alloSCT was performed, or who may require rapid immune suppression withdrawal as pre-emergent treatment of early malignancy relapse.
- •Active treatment in a clinical study of any investigational agent within 30 days prior to Cycle 1 Day1, or within 5 half-lives of the study treatment, whichever is longer
- •SR-osGVHD occurring after a non-scheduled donor lymphocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. Patients who have received a scheduled DLI as part of their transplant procedure (up to day 120) and not for management of malignancy relapse are eligible.
- •Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration and contraindications of study drug/study procedure and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.
- •Presence of severely impaired renal function defined by serum creatinine > 2 mg/dL (>176.8μmol/L), renal dialysis requirement, or have estimated creatinine clearance <30 ml/min measured or calculated by Cockroft Gault equation (confirmed within 48 hours prior to study treatment start).
结局指标
主要结局
Assessment by ORR at the week 25 (Cycle 7 Day 1) visit. The ORR is defined as the proportion of patients demonstrating a CR or PR without the requirement of additional systemic therapies for an earlier progression, mixed response or non-response. Scoring of response will be relative to the organ score at the time of baseline assessment. Missing values will be counted as non-responders
Assessment by ORR at the week 25 (Cycle 7 Day 1) visit. The ORR is defined as the proportion of patients demonstrating a CR or PR without the requirement of additional systemic therapies for an earlier progression, mixed response or non-response. Scoring of response will be relative to the organ score at the time of baseline assessment. Missing values will be counted as non-responders
次要结局
- FFS is defined as time from start of treatment to the earliest recurrence of underlying disease, start of a new systemic treatment for osGVHD, or death, or the date the patient is last seen alive without event (censored observation)
- To evaluate change in the mLSS (Symptom control). Response defined as a ≥7-point reduction from baseline in total symptom score (evaluation at week 25).
- OS is defined as time from start of treatment to the date of death from any cause, or the date the patient is last seen alive (censored observation)
- BOR - Proportion of patients who achieved OR (CR+PR) at any time point (up to Cycle 7 day 1 or the start of additional systemic therapy for osGVHD)
- DOR is assessed for responders only. DOR is defined as the time from first response until osGVHD progression, death, or the date of change/addition of systemic therapies for osGVHD, or the date the patient is last seen alive without event (censored observation)
- NRM is defined as the time from start of treatment to date of death not preceded by underlying disease relapse/recurrence. Underlying disease relapse/ recurrence is considered as a competing event
- Response according to organs; Scoring of response will be relative to the organ score at the time of baseline assessment
- To assess the proportion of patients with ≥50% reduction in daily steroid dose at week 25
- To assess the proportion of patients who successfully tapered off all steroids at week 25
- MR is defined as the time from start of treatment to hematologic malignancy relapse/recurrence. Calculated for patients with underlying hematologic malignant disease. NRM is considered as a competing event.
- Time to response is defined as time from treatment start to the date of first documentation of PR or CR. Death without prior response will be considered to be a competing event.
- Changes in immune cell phenotype (T cells (CD3, CD4 and CD8), NK cells (CD56, CD3-, TCR-), NKT cells (CD3+ CD1d Tetramer+), monocytes (CD11bCD14); neutrophils (CD11b, CD15)) B cells (CD21low) and immune metabolism during treatment as described in section 7.6.16.
- Change in FACT-BMT from baseline to each visit where measured.
- The AE and SAE reporting and documentation period begins with the ICF signature and ends 30 days after last treatment with belumosudil, further information see section 10.
- The incidence of AEs defined by preferred term (PT) according to MedDRA will be calculated and analysed.
研究者
Dr. Kristina Maas-Bauer
Scientific
Medical Center - University Of Freiburg
研究点 (1)
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