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

July 19, 2024 updated by: Xianmin Song, MD, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

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

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.

Study Overview

Status

Recruiting

Conditions

Study Type

Observational

Enrollment (Estimated)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Xianmin Song, MD
Phone Number: +86 13501672508
Email: shongxm@139.com

Study Locations

China
- Shanghai
  - Shanghai, Shanghai, China, 200080
    - Recruiting
    - Shanghai General Hospital
    - Principal Investigator:
      
      Xianmin Song, MD
    - Contact:
      
      Xianmin Song, MD
      
      Phone Number: 3175 +86 21 63240090
      
      Email: shongxm@139.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Adult

Accepts Healthy Volunteers

Sampling Method

Non-Probability Sample

Study Population

Outpatient and inpatient patients

Description

Inclusion Criteria:

Age between 18 and less than 55 years, regardless of gender.
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.
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.
Hematopoietic cell transplantation comorbidity index (HCT-CI) score ≤ 2.
ECOG (Eastern Cooperative Oncology Group) performance status: 0-2.
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%.
Patients must have the ability to understand and be willing to participate in this study and sign an informed consent form.

Exclusion Criteria:

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.
ECOG > 2.
HCT-CI score ≥ 3.
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.
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.
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.
HIV-infected individuals.
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.
Pregnant or breastfeeding women.
Fertile males and females unwilling to use contraception during the treatment period and for 12 months after treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1y and 2y-PFS Time Frame: 2023-2027	1-year and 2-year progression-free survival (PFS) rates post-transplant	2023-2027

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
aGVHD Time Frame: 2023-2025	acute graft-versus-host disease (GVHD) within 180 days post-transplant	2023-2025
cGVHD Time Frame: 2023-2027	cumulative incidence of chronic GVHD at 2 years post-transplant	2023-2027
CMV and EBV reactivation Time Frame: 2023-2026	the incidence of CMV and EBV reactivation within 1 year	2023-2026
1y and 2y-CIR Time Frame: 2023-2027	cumulative relapse rates (CIR) at 1 year and 2 years post-transplant	2023-2027
1y and 2y-OS Time Frame: 2023-2027	overall survival (OS) at 1 year and 2 years post-transplant	2023-2027
GRFS Time Frame: 2023-2027	graft-versus-host disease-free, relapse-free survival (GRFS) at 2 years post-transplant	2023-2027
NRM Time Frame: 2023-2027	non-relapse mortality (NRM) at 2 years post-transplant	2023-2027

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Investigators

Principal Investigator: Xianmin Song, MD, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 20, 2024

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

January 1, 2027

Study Registration Dates

First Submitted

October 27, 2023

First Submitted That Met QC Criteria