Efficacy and Safety of the CloB2M (Clofarabine Combined With Busulfan and Melphalan) Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation for Adult Patients With Acute Myeloid Leukemia in First Complete Remission

Официальное название

Efficacy and Safety of the CloB2M (Clofarabine Combined With Busulfan and Melphalan) Conditioning Regimen in Allogeneic Hematopoietic Stem Cell Transplantation for Adult Patients With Acute Myeloid Leukemia in First Complete Remission: An Open-Label, Prospective, Single-Arm Clinical Trial

Обзор

This is a single-center, prospective, exploratory clinical study. It plans to enroll 30 adult patients with acute myeloid leukemia (AML) who have achieved first complete remission (CR1) after induction therapy and meet the indications for allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim is to evaluate the efficacy and safety of allo-HSCT following conditioning regimens with clofarabine, busulfan and melphalan.

Вмешательства

• Препарат CloB2M (Clofarabine Combined With Busulfan and Melphalan) Conditioning Regimen
  CloB2M (Clofarabine Combined With Busulfan and Melphalan) Conditioning Regimen

Первичные конечные точки

• 2-year Overall Survival（OS）rate [Срок оценки: 2 years.]

Вторичные конечные точки (8)

• 1-year Overall Survival（OS）rate [Срок оценки: 1 year]
• 1-year Relapse-Free Survival(RFS) rate,2-years Relapse-Free Survival(RFS) rate [Срок оценки: 1-year,2-years]
• Day 100 non-relapse mortality (NRM) rate after transplantation [Срок оценки: as the non-relapse mortality at Day 100 post-transplantation.]
• 2-year cumulative incidence of relapse (CIR) after transplantation [Срок оценки: 2-year]
• Minimal Residual Disease(MRD) negative conversion rate [Срок оценки: Bone marrow MRD levels are monitored at 1, 3, 6, 9 and 12 months after hematopoietic stem cell transplantation.]
• Time to Absolute Neutrophil Count(ANC) engraftment and time to Platelet Count(PLT) engraftment (hematopoietic reconstitution time) [Срок оценки: Time to ANC engraftment is defined as the first day of sustained absolute neutrophil count ≥ 0.5×10⁹/L for three consecutive days after transplantation. Time to PLT engraftment is defined as the first day of sustained platelet count ≥ 20×10⁹/L for seven]
• Incidence of Graft-versus-Host Disease(GVHD) [Срок оценки: The incidences of acute graft-versus-host disease (aGVHD) and severe (Grade III-IV) aGVHD within 100 days after hematopoietic stem cell transplantation, as well as chronic graft-versus-host disease (cGVHD) within 2 years after transplantation.]
• The severity of adverse events and the number of participants with treatment-related adverse events as assessed by CTCAE v5.0. [Срок оценки: From start of treatment to 2 years post-treatment.]

Критерии участия

Критерии включения

• 1.Aged from 18 to 60 years inclusive, with no restriction on gender;
• 2.Patients diagnosed with acute myeloid leukemia (AML, excluding acute promyelocytic leukemia, APL) by bone marrow morphological, immunological and genetic examinations according to the 2022 World Health Organization (WHO) classification, who have achieved first complete remission (CR1) after induction therapy;
• 3.Meeting any of the following criteria upon clinical evaluation:

• AML classified as intermediate or adverse genetic risk according to the 2022 ELN genetic risk stratification;
• AML with positive measurable residual disease (MRD) before transplantation;
• 4.Eastern Cooperative Oncology Group Performance Status (ECOG PS): 0-2;
• 5.Estimated survival time more than 6 months;
• 6.Meeting the indications for allogeneic hematopoietic stem cell transplantation (allo-HSCT), and having an eligible hematopoietic stem cell donor with qualified physical examination, including HLA-matched sibling donor, unrelated donor (high-resolution HLA 9-10/10 matched) or haploidentical related donor;
• 7.Adequate major organ function meeting the following criteria:

• Total bilirubin (TBIL) ≤ 2 times the upper limit of normal (ULN); Alanine transaminase (ALT) and Aspartate transaminase (AST) ≤ 3 × ULN;
• Serum creatinine (Cr) ≤ 1.5 × ULN, or estimated creatinine clearance ≥ 50 mL/min calculated by the Cockcroft-Gault glomerular filtration formula;
• Coagulation function meeting the following standards: Prothrombin time (PT), activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5 × ULN (without anticoagulant therapy);
• Electrocardiogram showing no acute myocardial infarction or severe arrhythmia; Echocardiography with left ventricular ejection fraction (LVEF) ≥ 50%, without significant cardiomegaly, valvular heart disease or congenital heart disease;
• Pulmonary function tests: FEV1, FVC and DLCO ≥ 60% of predicted value;
• 8.Willing to provide available diagnostic evidence or undergo bone marrow aspiration and biopsy prior to study treatment, and agree to receive regular bone marrow aspiration and biopsy after study treatment;
• 9.Must sign the informed consent form prior to study enrollment, signed by the patient personally or immediate family members. If signature by the patient is deemed detrimental to disease treatment based on clinical condition assessment, the informed consent shall be signed by the legal guardian or immediate family member of the patient.

Критерии исключения

• 1.Refractory/relapsed AML;
• 2.Known hypersensitivity to any drugs in the conditioning regimen or their excipients;
• 3.Major surgery within the past 4 weeks (excluding diagnostic surgical procedures);
• 4.History of or concurrent other malignant tumors (excluding well-controlled non-melanoma basal cell carcinoma of the skin, breast/cervical carcinoma in situ, and other malignancies well controlled without treatment for more than five years);
• 5\. Uncontrolled systemic diseases (such as uncontrolled hypertension, diabetes mellitus, etc.);
• 6.Active hepatitis B or hepatitis C infection:（Hepatitis B virus surface antigen positive, hepatitis B core antibody positive with HBV-DNA level exceeding 1×103 copies/mL;Hepatitis C virus RNA level exceeding 1×10 3 copies/mL）;
• 7.Uncontrolled ongoing infection, or patients requiring mechanical ventilation or with hemodynamic instability;
• 8.Patients with psychiatric disorders or other medical conditions who are unable to comply with study treatment and monitoring requirements;
• 9.Participation in another ongoing clinical trial, or enrollment in any other drug clinical trial within the past 1 month;
• 10.Pregnant or lactating females, and patients who refuse to use effective contraception during the study period;
• 11.Patients who are unable to understand the trial protocol, adhere to medication instructions, or refuse to sign the informed consent form;
• 12.Patients deemed ineligible for enrollment by the investigator.

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

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07644481 · IIT2026038

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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