Intensive conditioning for myeloid cancers with extramedullary involvement

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 testing a new treatment plan using specific medications before a stem cell transplant to see if it helps people with myeloid cancers that have spread beyond the bone marrow feel better and have better outcomes.

Quick facts

• Study type: Observational
• Enrollment: 50 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (Academic / other)
• Drugs / interventions: fludarabine
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06111612 on ClinicalTrials.gov

What this trial studies

This multicenter, single-arm, prospective clinical trial evaluates the safety and efficacy of an intensive conditioning regimen using thiotepa, busulfan, fludarabine, and cytarabine for patients undergoing allogeneic hematopoietic stem cell transplantation for myeloid malignancies that have spread beyond the bone marrow. The regimen is administered over a series of days leading up to the stem cell infusion, with follow-up bone marrow examinations scheduled at regular intervals post-transplant. The study aims to assess how well this approach can control the disease and improve patient outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 55 with specific myeloid malignancies and extramedullary lesions who have achieved hematological remission.

Not a fit: Patients older than 55 or those without extramedullary involvement or suitable stem cell donors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective option for patients with myeloid malignancies that have extramedullary involvement.

How similar studies have performed: While there is limited information on similar studies, the approach of intensive conditioning in hematopoietic stem cell transplantation has shown promise in other contexts.

Eligibility 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.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai General Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Xianmin Song, MD — Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Study coordinator: Xianmin Song, MD

Conditions Acute Myeloid Leukemia; Myelodysplastic Neoplasm; Chronic Myelomonocytic Leukemia; Myeloid Sarcoma; Extramedullary Myeloid Tumor