Thiotepa-Containing Conditioning Regimen for Allogeneic HSCT in Chronic Myelomonocytic Leukemia

Официальное название

Prospective Single-Arm Clinical Study of Thiotepa-Containing Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation in Chronic Myelomonocytic Leukemia

Обзор

This is a prospective, single-arm clinical study. It aims to evaluate the effectiveness and safety of a conditioning regimen containing thiotepa (in combination with busulfan and fludarabine, with or without ATG) of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with chronic myelomonocytic leukemia (CMML) who have an intermediate-2 or high-risk prognosis. The main goal is to evaluate 1 year RFS and OS. Other goals include assessing engraftment, overall survival, transplant-related complications, and side effects. A total of 31 participants will be enrolled.

Вмешательства

• Препарат TBF regimen
  Intravenous thiotepa 5 mg/kg/d on days -11,-10; busulfan 3.2 mg/kg/d on days -8,-7,-6; fludarabine 30 mg/m²/d on days -6 to -2; ATG per donor type (haplo/unrelated: 2.5 mg/kg/d days -5 to -2; MSD: 1.125 mg/kg/d days -5 to -2). Allogeneic stem cells infused on day 0. GVHD prophylaxis: CsA, MMF, MTX per protocol.

Первичные конечные точки

• One-year relapse-free survival (RFS) after allogeneic hematopoietic stem cell transplantation [Срок оценки: At 12 months after allogeneic hematopoietic stem cell transplantation.]

Вторичные конечные точки (7)

• One-year overall survival (OS) [Срок оценки: At 12 months after allogeneic hematopoietic stem cell transplantation.]
• One-year cumulative incidence of relapse (RR) [Срок оценки: At 12 months after allogeneic hematopoietic stem cell transplantation.]
• One-year non-relapse mortality (NRM) [Срок оценки: At 12 months after allogeneic hematopoietic stem cell transplantation.]
• Regimen toxicity at day +30 [Срок оценки: Up to day +30 post-transplant]
• Incidence and severity of adverse events (AEs) [Срок оценки: At 12 months after allogeneic hematopoietic stem cell transplantation.]
• Incidence and severity of acute graft-versus-host disease (aGVHD) [Срок оценки: Up to day +100 post-transplant]
• Incidence and severity of chronic graft-versus-host disease (cGVHD) [Срок оценки: From day +100 up to 1 year post-transplant]

Критерии участия

Критерии включения

• Age ≥ 18 years, any sex/gender.
• Confirmed diagnosis of chronic myelomonocytic leukemia (CMML) according to the 2022 WHO classification.
• Intermediate-2 or high-risk CMML based on CPSS or CPSS-mol score, and planned to receive allo-HSCT.
• Has a suitable hematopoietic stem cell donor:
• For haploidentical donor: at least 5/10 HLA match at HLA-A, -B, -C, -DQB1, and -DRB1.
• For unrelated donor: at least 9/10 HLA match at the same five loci.
• For matched sibling donor: 10/10 HLA match at the same five loci.
• Hematopoietic cell transplantation comorbidity index (HCT-CI) ≤ 2, with generally good health and no significant organ abnormalities or major comorbidities.
• Adequate organ function as defined below:
• Left ventricular ejection fraction (LVEF) ≥ 50%, and no uncontrolled tachycardia or bradycardia-tachycardia syndrome.
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT ≤ 2 × ULN; AST ≤ 2 × ULN.
• Serum creatinine ≤ 1.5 × ULN.
• Baseline oxygen saturation > 92%.
• Pulmonary function: DLCO (corrected for hemoglobin) ≥ 40%, FEV1 ≥ 50%.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Agrees not to participate in any other interventional study during the treatment period.
• Willing and able to provide written informed consent, understand the nature, purpose, and procedures of the study, and voluntarily comply with study requirements.

Критерии исключения

• Previous allogeneic HSCT for CMML that later relapsed.
• Unwilling or unable to receive the study treatment regimen.
• Active hepatitis B or C, or chronic active hepatitis; known human immunodeficiency virus (HIV) infection.
• Active uncontrolled infection, including: hemodynamic instability related to infection, new or worsening signs/symptoms of infection, new infection lesions on imaging, or persistent fever without explanation despite no symptoms/signs.
• History of stroke or intracranial hemorrhage within 6 months before enrollment.
• Known pregnancy (positive urine pregnancy test), or currently breastfeeding.
• Diagnosis of another malignancy within the past 2 years, except for localized skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, breast cancer, or localized prostate cancer (Gleason score ≤ 6) that has been treated with curative intent.
• Any other condition that, in the investigator's judgment, makes the patient unsuitable for study participation.

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 · 1 центр

• Peking University People's Hospital — Пекин

Идентификаторы

NCT: NCT07588594 · 2025PHD048-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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