Clinical trial NCT06548958: A Single-Arm, Prospective Study of TBI+BUMEL as Conditioning for SCT2 in Patients With Malignant Hematologic Diseases
Official title: A Single-Arm, Prospective Clinical Study of Total Body Irradiation Combined With Busulfan and Melphalan (TBI+BUMEL) as a Conditioning Regimen for Second Hematopoietic Stem Cell Transplantation in Patients With Malignant Hematologic Diseases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Malignant Hematological Diseases
Keywords: Second Allogeneic Hematopoietic Stem Cell Transplantation
Malignant Hematological Diseases
Total Body Irradiation
Melphalan
Conditioning Regimen
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2024-08-12
Enrollment: 40
Sex: ALL
Minimum age (years): 14
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Each year, over 20,000 patients in China undergo hematopoietic stem cell transplantation (HSCT). Unfortunately, the prognosis in patients with disease relapse or graft failure is often inferior. A second allogeneic hematopoietic stem cell transplantation (SCT2) has emerged as a vital salvage therapy option. Despite varying prognoses, most patients undergoing SCT2 have a five-year overall survival (OS) rate of less than 30%. The primary challenges of SCT2 include treatment strategy, immune regulation, complication management, and transplantation technique improvements. By optimizing these key aspects, SCT2 can effectively address issues that arose after the first transplant, reduce complications, and provide more effective treatment for patients.

Clinical practice indicates that SCT2 is crucial in treating various hematologic diseases. For patients who failed the first transplant (SCT1), SCT2 can more effectively treat the primary disease, provide timely hematopoietic engraftment, extend survival time, and improve the quality of life. Additionally, the successful application of SCT2 provides clinicians with more treatment options and hope. Currently, the modified BU/CY conditioning regimen, which consists of busulfan (BU) and cyclophosphamide (CY), is commonly used in SCT1 in China. However, for patients who relapse after SCT1, these drugs may become ineffective, and the physical condition often worsens, with a higher likelihood of infections and organ dysfunction. Therefore, finding new conditioning regimens is crucial.

Studies have shown that a melphalan (MEL)-based conditioning regimen may have better outcomes for patients with acute myeloid leukemia (AML) compared to a Cy-based regimen. The Conditioning regimen that includes total body irradiation (TBI) has also been considered effective for patients with acute leukemia. Thus, low-dose TBI combined with a BU + MEL regimen could be a promising conditioning regimen for SCT2. In the investigators' preliminary studies, three patients who underwent SCT2 with this regimen successfully achieved engraftment and were discharged.

Based on this, the investigators plan to conduct a clinical study to observe the effects of the TBI+BUMEL regimen combined with SCT2 on the engraftment rate, disease relapse rate, GVHD incidence, and survival rate in patients with malignant hematologic diseases who relapsed after SCT1.

Detailed description: The primary challenges of SCT2 include:

1. treatment strategy: eliminating residual tumor cells and addressing graft failure;
2. immune regulation: adjusting the immune system to ensure successful engraftment of new stem cells;
3. complication management: due to the poor physical condition of patients after the first transplant (SCT1), the risk of complications after SCT2 is high. This necessitates special attention to the prevention and management of post-transplant complications;
4. transplantation technique improvements: more rigorous donor screening, HLA typing, monitoring, and supportive treatment during the transplant procedure.

Eligibility criteria: Inclusion Criteria:

1. Gender is not limited, patients between 14 to 70 years old (including critical value);
2. Malignant hematological diseases (acute/chronic myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, malignant lymphoma, etc.) diagnosed by bone marrow aspiration or biopsy according to the WHO diagnostic criteria, after the first hematopoietic stem cell transplantation, due to various reasons (including but not limited to disease relapse or graft failure) have indications for a second hematopoietic stem cell transplantation;
3. The indexes of cardiac function, liver and kidney function were within the following limits: (1) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3× Upper limit of normal (ULN); (2)Total bilirubin ≤ 3×ULN; (3) Serum creatinine ≤ 2×ULN or creatinine clearance ≥ 40mL/min; (4) Left ventricular ejection fraction (LVEF) as measured by echocardiography or multi-gated acquisition (MUGA) scan is within the normal range (\> 50%);
4. Having a suitable allogeneic hematopoietic stem cell donor;
5. Expected survival ≥3 months;
6. Karnofsky (KPS) score ≥60%, Eastern Tumor Cooperative group (ECOG) status ≤ 2;
7. Patient fully understood the nature of the study, and voluntarily participates and signs informed consent.

Exclusion Criteria:

1. Patients had serious adverse reactions to investigational drugs such as allergies;
2. Patients with a history of immunodeficiency, or other acquired or congenital diseases, immunodeficiency diseases, and a history of organ transplantation;
3. Patients with hypertension, ventricular arrhythmia requiring clinical intervention, acute coronary syndrome, congestive heart failure, stroke, or other grade III or higher cardiovascular events within 6 months;
4. Received Class II or higher surgery within 4 weeks prior to enrollment;
5. Patients with active viral infections;
6. Pregnant or lactating patients;
7. The patient is currently participating in another clinical studies;
8. Patients deemed unsuitable for inclusion by other investigators.

Primary outcomes:
measure: The cumulative incidence of neutrophil engraftment and platelet engraftment
timeFrame: on day 28±7 following SCT2
measure: The time to reconstitution of hematopoiesis
timeFrame: on day 28±7 following SCT2
measure: The cumulative incidence of transplant-related mortality (TRM)
timeFrame: within 100 days following SCT2
Secondary outcomes:
measure: The cumulative incidence and grade of graft-versus-host disease (GVHD)
timeFrame: within 1 year following SCT2
measure: The cumulative incidence of relapse
timeFrame: within 1 year following SCT2
measure: Overall survival rate
timeFrame: within 1 year following SCT2
measure: The cumulative incidence of adverse events
timeFrame: within 1 year following SCT2
Other outcomes:
Locations:
city: Suzhou
country: China
facility: Hematology Department, The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Depei Wu, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Soochow University
name: Xiaojin Wu, Prof.
role: PRINCIPAL_INVESTIGATOR
References: