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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Myelomonocytic Leukemia (CMML)
• Intervention / Treatment: Drug: TBF regimen

• Study Type: Interventional
• Enrollment (Estimated): 31
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yuqian Sun, MD; Phone Number: +86 13717833825; Email: sunyuqian83@hotmail.com
• Study Contact Backup: Name: Xueyi Luo, MD; Phone Number: +86 13811936698; Email: lll_xxx_yyy@126.com

Study Locations

• China
  • Beijing, China, 100044
    • Recruiting
    • Peking University People's Hospital
    • Contact: Yuqian Sun, MD; Phone Number: +86 010-88326666; Email: sunyuqian83@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm: Thiotepa + Busulfan + Fludarabine ± ATG; Patients with intermediate-2 or high-risk chronic myelomonocytic leukemia (CMML) per CPSS/CPSS-mol criteria, who are scheduled to receive allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a thiotepa-containing conditioning regimen.	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.; Other Names: TBF (Thiotepa, Busulfan, Fludarabine) ± ATG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
One-year relapse-free survival (RFS) after allogeneic hematopoietic stem cell transplantation	Time from stem cell infusion to hematologic/extramedullary relapse or death, censored at 12 months for event-free participants.	At 12 months after allogeneic hematopoietic stem cell transplantation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
One-year overall survival (OS)	Overall survival is defined as the time from stem cell infusion to death from any cause. Participants alive at 12 months are censored at the last follow-up.	At 12 months after allogeneic hematopoietic stem cell transplantation.
One-year cumulative incidence of relapse (RR)	Relapse is defined as recurrence of CMML . Non-relapse mortality is treated as a competing risk.	At 12 months after allogeneic hematopoietic stem cell transplantation.
One-year non-relapse mortality (NRM)	Non-relapse mortality is defined as death from any cause other than disease relapse or progression. Relapse is treated as a competing risk.	At 12 months after allogeneic hematopoietic stem cell transplantation.
Regimen toxicity at day +30	Toxicity is graded according to NCI CTCAE v5.0. Any grade 3-5 non-hematologic toxicity occurring within 30 days after stem cell infusion is reported.	Up to day +30 post-transplant
Incidence and severity of adverse events (AEs)	AEs are coded using MedDRA and graded per NCI CTCAE v5.0. All AEs, serious AEs (SAEs), and AEs leading to treatment discontinuation are summarized.	At 12 months after allogeneic hematopoietic stem cell transplantation.
Incidence and severity of acute graft-versus-host disease (aGVHD)	Acute GVHD is diagnosed and graded according to the modified Glucksberg criteria or MAGIC criteria. Both overall incidence and grade II-IV/III-IV severity are reported.	Up to day +100 post-transplant
Incidence and severity of chronic graft-versus-host disease (cGVHD)	Chronic GVHD is diagnosed and graded according to the NIH consensus criteria (mild, moderate, severe). Overall incidence and severity distribution are reported.	From day +100 up to 1 year post-transplant

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Jiangsu Hengrui Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Yuqian Sun, MD, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: May 6, 2026
• First Submitted That Met QC Criteria: May 6, 2026
• First Posted (Actual): May 15, 2026

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Thiotepa; Chronic Myelomonocytic Leukemia (CMML); Hematopoietic Stem Cell Transplantation (HSCT)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Myelomonocytic, Chronic; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons, Acyclic; Hydrocarbons; Alkanes; Alcohols; Butylene Glycols; Glycols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Sulfonic Acids; Sulfur Acids; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Busulfan; Thiotepa; fludarabine
• Other Study ID Numbers: 2025PHD048-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared with other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No