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

Official title

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

Overview

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.

Interventions

• Drug 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.

Primary outcome measures

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

Secondary outcome measures (7)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking University People's Hospital — Beijing

Identifiers

NCT: NCT07588594 · 2025PHD048-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗