Intensive Conditioning With Thiotepa Combined With Bu/Flu/Ara-C in Allo-HSCT for Myeloid Malignancies With Extramedullary Involvement

Study Purpose

This study is a multicenter, single-arm, prospective phase II clinical trial that evaluates the efficacy and safety of an intensive conditioning regimen with thiotepa combined with busulfan, fludarabine, and cytarabine for allogeneic hematopoietic stem cell transplantation in the treatment of myeloid malignancies with extramedullary involvement. The conditioning regimen includes thiotepa at a dose of 5mg/kg/d from d -9 to d -8 (2 days), fludarabine at 30mg/m2/d from d -7 to d -3 (5 days), cytarabine at 1-1.5g/m2/d from d -7 to d -3 (5 days), and busulfan at 3.2mg/kg/d from d -5 to d -3 (3 days). Conditioning begins on day -9, and donor hematopoietic stem cell infusion is performed on day 0. All patients will undergo bone marrow examination on day 14 and day 28 post-transplant, followed by bone marrow examinations every 30 days within the first year after transplantation, and every 60 days within the second year after transplantation. If disease relapse is suspected during the follow-up period, bone marrow or extramedullary relapse site examinations will be conducted at any time. The primary study endpoints are the 1-year and 2-year progression-free survival (PFS) rates post-transplant. Secondary study endpoints include the incidence of acute graft-versus-host disease (GVHD) within 180 days post-transplant, cumulative relapse rates at 1 year and 2 years post-transplant, 1-year and 2-year overall survival (OS), graft-versus-host disease-free, relapse-free survival (GRFS), non-relapse mortality (NRM), cumulative incidence of chronic GVHD, and the incidence of Cytomegalovirus （CMV）and Epstein-Barr virus（EBV）reactivation within 1 year.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years - 55 Years
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Age between 18 and less than 55 years, regardless of gender. 2. Criteria for myeloid tumors with extramedullary involvement: 1. AML (Acute Myeloid Leukemia) with at least one extramedullary lesion achieving hematological remission (CR1 or CR2) after induction therapy. 2. MDS (Myelodysplastic Syndrome) with at least one extramedullary lesion and bone marrow blast percentage ≥ 5% achieving hematological CR after treatment; CMML (Chronic Myelomonocytic Leukemia) with at least one extramedullary lesion (diagnosed according to WHO standards) achieving hematological CR after treatment. 3. Control and remission of extramedullary lesions, including those in the central nervous system, testes, skin, and other extramedullary tissues. 4. Granulocytic sarcoma with or without bone marrow involvement, and achieving remission after treatment. 3. Patients must have a suitable hematopoietic stem cell donor: 1. Related donors must have at least 5/10 matches for HLA-A, -B, -C, -DQB1, and

- DRB1.

2. Unrelated donors must have at least 8/10 matches for HLA-A, -B, -C, -DQB1, and.

- DRB1.

4. Hematopoietic cell transplantation comorbidity index (HCT-CI) score ≤ 2. 5. ECOG (Eastern Cooperative Oncology Group) performance status: 0-2. 6. Adequate liver, kidney, and cardiopulmonary function, meeting the following requirements: 1. Serum creatinine ≤ 1.5x ULN (the upper limit of normal). 2. Cardiac function: Ejection fraction ≥ 50%. 3. Baseline oxygen saturation > 92%. 4. Total bilirubin ≤ 1.5 x ULN; ALT and AST ≤ 2.0 x ULN. 5. Pulmonary function: DLCO (corrected for hemoglobin) ≥ 40% and FEV1 (Forced Expiratory Volume in 1 second) ≥ 50%. 7. Patients must have the ability to understand and be willing to participate in this study and sign an informed consent form.

Exclusion Criteria:

1. History of malignancies other than myeloid tumors within the 5 years prior to screening, except for adequately treated in situ cervical cancer, basal cell carcinoma, squamous cell carcinoma of the skin, and curatively treated localized prostate cancer or ductal carcinoma in situ. 2. ECOG > 2. 3. HCT-CI score ≥ 3. 4. Any unstable systemic diseases, including but not limited to unstable angina, recent cerebrovascular accidents or transient ischemic attacks within the 3 months prior to screening, myocardial infarction within the 3 months prior to screening, congestive heart failure (New York Heart Association [NYHA] class ≥ III), severe arrhythmias requiring drug treatment after pacemaker implantation, significant liver, kidney, or metabolic diseases, and pulmonary arterial hypertension. 5. Active, uncontrolled infections, including those associated with hemodynamic instability, new or worsening infection symptoms or signs, new infectious lesions on imaging, or persistent unexplained fever without signs or symptoms of infection. 6. Conditions requiring treatment such as grade 2 or higher seizures, paralysis, aphasia, recent severe cerebral infarction, severe traumatic brain injury, dementia, Parkinson's disease, or schizophrenia. 7. HIV-infected individuals. 8. Active hepatitis B (HBV) or active hepatitis C (HCV) requiring antiviral therapy. Patients at risk of HBV reactivation, are defined as those who are positive for hepatitis B surface antigen or core antibody without receiving antiviral therapy. 9. Pregnant or breastfeeding women. 10. Fertile males and females unwilling to use contraception during the treatment period and for 12 months after treatment.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06111612
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Xianmin Song, MD
Principal Investigator Affiliation	Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Acute Myeloid Leukemia, Myelodysplastic Neoplasm, Chronic Myelomonocytic Leukemia, Myeloid Sarcoma, Extramedullary Myeloid Tumor

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

Xianmin Song, MD

[email protected]

+86 13501672508

For additional contact information, you can also visit the trial on clinicaltrials.gov.

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