NCT06125483 TBI/Flu/Bu/Mel Combined With Secondary UCBT in Patients With Hematological Malignancies Who Relapsed After Allo-HSCT
| NCT ID | NCT06125483 |
| Status | Recruiting |
| Phase | — |
| Sponsor | The First Affiliated Hospital of Soochow University |
| Condition | Hematopoietic Malignancy |
| Study Type | INTERVENTIONAL |
| Enrollment | 38 participants |
| Start Date | 2023-11-01 |
| Primary Completion | 2025-04-30 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
This trial targets 38 participants in total. It began in 2023-11-01 with a primary completion date of 2025-04-30.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief Summary
About 33% of patients with myeloid or lymphoid malignancies experience relapse with HLA loss after haplo-HSCT. Due to the specificity of HLA-loss relapse, the 2019 European Society for Blood and Marrow Transplantation (EBMT) pointed out that for diagnosed HLA-loss patients, it is recommended to use different HLA-haploidentical donors, and lymphocyte infusions from the original donor cannot improve the prognosis. Clinical studies have found that second transplantation can achieve prolonged disease-free survival than chemotherapy for patients with HLA loss, and it may be an effective treatment strategy for these patients. However, due to the high standard of second hematopoietic stem cell transplantation (HSCT), not all patients can find suitable donors. Since the first successful application of umbilical cord blood transplantation (UCBT) by Gluckman et al. in France in 1988 for the treatment of Fanconi anemia, umbilical cord blood (UCB) has been widely used as a reliable source for HSCT in the treatment of hematological diseases. In 1998, Professor Yongping Song led the first successful UCBT in the treatment of leukemia, opening up the path of it in China. Compared with peripheral blood stem cell transplantation (PBST), UCBT has a higher engraftment rate. UCB contains more primitive and purer stem cells than bone marrow hematopoietic stem cells. UCBT can be performed with only 4 HLA matches, and the degree of rejection, the risk of disease relapse, and the incidence of chronic graft-versus-host disease (cGVHD) are all relatively low, greatly improving the survival of patients. Although UCBT has been a potential treatment for second transplantation, the effective conditioning regimen is still under discussion. Improving the incidence of engraftment , the tolerance of conditioning, and reducing transplant-related mortality (TRM) are issues of great concern in second transplantation. A standard RIC regimen composed of fludarabine (200mg/m2) combined with cyclophosphamide (50mg/kg) and 2Gy or 3Gy total body irradiation (TBI) is the most common conditioning regimen used in UCBT. Although the tolerance of this RIC is acceptable, the relapse rate after transplantation is relatively high, and the implantation failure rate is also high in high-risk populations. The inclusion of thiotepa (10mg/kg) combined with fludarabine, cyclophosphamide, and 4Gy TBI in an intensified version of the RIC regimen has improved the engraftment rate without increasing TRM. In addition, studies have also confirmed that increasing the dose of TBI can improve engraftment in transplant recipients at high risk of UCBT failure. The fludarabine/busulfan/melphalan (Flu/Bu/Mel) conditioning regimen was first used for salvaging UCBT in unresponsive hematological malignancies in 2016 and achieved good clinical outcomes. Subsequently, several transplant centers in Japan adopted the Flu/Bu/Mel conditioning regimen for UCBT and confirmed that, compared with the Flu/Bu4 regimen, it not only improved overall survival (OS) but also reduced disease relapse rate without increasing TRM. A recent multicenter retrospective study of UCBT in patients with acute myeloid leukemia in remission found that compared with the TBI/Cy conditioning regimen, the Flu/Bu/Mel conditioning regimen improved the engraftment rate and exerted the GVL effect, reducing NRM and improving OS. Based on the above, TBI/Flu/Bu/Mel as a conditioning regimen for secondary UCBT in patients with hematological malignancies who relapsed after allo-HSCT is safe and feasible, and is expected to improve the prognosis of these patients. Therefore, based on existing clinical experience with research evidence, our center plans to conduct a clinical study of low-dose TBI and FBM as a conditioning regimen for secondary UCBT in patients with hematological malignancies who relapsed after allo-HSCT, observing the improvement in the cumulative incidence of engraftment, disease relapse, GVHD, and survival rate in patients who received this regimen.
Eligibility Criteria
Inclusion Criteria: 1. Gender is not limited, patients between 10 to 65 years old (including critical value); 2. According to the WHO diagnostic criteria, the diagnosis of hematological malignancies ( acute lymphoblastic leukemia, acute / chronic myeloid leukemia, etc. ) was confirmed by bone marrow puncture or biopsy after allogeneic hematopoietic stem cell transplantation. The definition of relapse includes the proportion of bone marrow blast cells \> 5 %, blast cells in peripheral blood ( excluding the use of G-CSF and GM-CSF ), or extramedullary leukemia infiltration; 3. Planned to received umbilical cord blood transplantation; 4. 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%); 5. Umbilical cord blood with HLA match ≥ 6/10; 6. Expected survival ≥3 months; 7. Karnofsky (KPS) score ≥60%, Eastern Tumor Cooperative group (ECOG) status ≤ 2; 8. 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. Patient was complicated with pulmonary infection, which was confirmed by imaging to be progressive; 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. Patients with active viral infections, including HIV, HBV, HCV, TP; 5. Pregnant or lactating patients; 6. The patient is currently participating in another clinical studies; 7. Patients deemed unsuitable for inclusion by other investigators.
Contact & Investigator
Xiaojin Wu, Prof.
PRINCIPAL INVESTIGATOR
The First Affiliated Hospital of Soochow University
Frequently Asked Questions
Who can join the NCT06125483 clinical trial?
This trial is open to participants of all sexes, aged 10 Years or older, up to 65 Years, studying Hematopoietic Malignancy. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
Is NCT06125483 currently recruiting?
Yes, NCT06125483 is actively recruiting participants. Contact the research team at wuxiaojin@suda.edu.cn for enrollment information.
Where is the NCT06125483 trial being conducted?
This trial is being conducted at Suzhou, China.
Who is sponsoring the NCT06125483 clinical trial?
NCT06125483 is sponsored by The First Affiliated Hospital of Soochow University. The principal investigator is Xiaojin Wu, Prof. at The First Affiliated Hospital of Soochow University. The trial plans to enroll 38 participants.