TFBC Combined With UCBT in the Treatment of High-risk Malignant Hematological Diseases

NCT05929092 | Recruiting DMC

• 1 other identifier: SOOCHOW-WXJ-2023-132
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

High-risk malignant hematological diseases refer to malignant hematological diseases, mainly include various types of leukemia, lymphoma, and multiple myeloma, with very poor prognoses, very short survival, and unsatisfactory outcomes. Chemotherapy, hypomethylating agents (HMA), radiotherapy, targeted therapy, immunotherapy, and hematopoietic stem cell transplantation (HSCT) are common treatments for high-risk malignant hematological diseases. Because of the multiple lines and long duration of exposure to chemotherapy drugs in patients with high-risk malignant hematological diseases, monotherapy is inefficient, and radiotherapy is used frequently as an adjunct treatment to HSCT. Conventional myeloablative conditioning regimens before HSCT are comprised of cyclophosphamide/total body irradiation (Cy/TBI) and busulfan/cyclophosphamide (Bu/Cy). The reduced-toxicity myeloablative conditioning regimen, FBC, is the combination of Bu, Cy, and fludarabine (Flu), which has a strong immunosuppressive effect to ensure the success of engraftment of donor cells. Compared to the conventional intensified chemotherapy regimens, HMA have certain advantages of efficacy and safety and are the first-line treatment options for patients with acute myeloid leukemia (AML). Although monotherapy improves survival rate, the response rate is low. What's more, it is difficult to achieve sustained remission and long-term benefits. The current research hotspots are HMA combined with chemotherapy, targeted drugs such as BCL-2 inhibitors, immunotherapy, and cell therapy. Targeted therapy and immunotherapy are effective, but show a high prevalence of relapse, heavy treatment burden, and the need for long-term maintenance. HSCT is an important therapy for the treatment of high-risk malignant hematological diseases, which could eliminate tumor cells through high-dose radiotherapy or chemotherapy, destroy the immune system of patients to prepare the engraftment of donor cells, and promote the reconstitution of hematopoiesis and immune recovery. HSCT has developed rapidly since the 1950s and has been performed in more than one million patients worldwide. HSCT is often the only definitive treatment available for patients with certain specific congenital or acquired diseases and is used in the treatment of many high-risk malignant hematological diseases. However, due to the strict criteria for HSCT, many patients do not have a matched donor. Since the first successful UCBT in a child with severe Fanconi anemia reported by Gluckman et al. in France in 1988, cord blood has been widely used as a graft source of hematopoietic stem cells for the treatment of hematological diseases. Cord blood is rich in hematopoietic stem cells, endothelial progenitor cells, mesenchymal stem cells, and other stem/progenitor cells, as well as natural killer cells, Treg cells, and other immune cells, which have strong self-renewal and proliferation ability and low immunogenicity. The hematologic growth factors produced by these cells could act on the formation of myeloid cells and granulocytes, which are beneficial to hematopoietic reconstruction and recovery. It contains a variety of cytokines such as thrombopoietin, erythropoietin, stem cell factor, and multi-class interleukins. Some cytokines such as stem cell factor, IL-6, and IL-11 are much higher in cord blood than in peripheral blood. The potential mechanism by which UCBT exerts its therapeutic effect in patients with hematological diseases is largely the result of the interaction of multiple growth factors and stem/progenitor cells with the organism. Compared with peripheral blood stem cell transplantation (PBST), UCBT has a higher transplantation rate, as cord blood stem cells are more primitive and purer than bone marrow stem cells. UCBT could be performed with four or more matches, and have a relatively lower rejection rate, lower relapse rate of malignant hematological diseases, and lower cumulative incidence of chronic graft-versus-host disease (GVHD), which greatly improves patient survival. Prof. Sun Zimin's team at Anhui Provincial Hospital was the first to use UCBT for the treatment of patients with AML and found that the cumulative incidence of chronic GVHD and relapse rate were significantly reduced. Based on the above, the TFBC regimen (TBI/Flu/Bu/Cy) combined with UCBT is safe and feasible for the treatment of patients with high-risk malignant hematological diseases, which has enormous potential to improve patient outcomes. Therefore, we designed this clinical study on the TFBC regimen combined with UCBT for the treatment of high-risk malignant hematological patients to observe the impact on the engraftment rate, relapse rate, the cumulative incidence of GVHD, and survival.

Conditions

Hematopoietic Stem Cell Transplantation; Malignant Hematological Diseases

Keywords

Umbilical Cord Blood Transplantation; Conditioning regimen

Outcome Measures

Primary Outcomes (3)

• The cumulative incidence of neutrophil engraftment and platelet engraftment

  Neutrophil and platelet engraftment is defined as the first occurrence of 3 consecutive days with an absolute neutrophil count of at least 0.5×109/L and a platelet count of over 20×109/L for 7 consecutive days without transfusion support.

  on day 28±7 following UCBT

• The time to reconstitution of hematopoiesis

  Recovery of hemopoietic function after treatment

  on day 28±7 following UCBT

• The cumulative incidence of transplant-related mortality (TRM)

  Transplant-related mortality was defined as mortality due to any cause other than disease progression within 100 days of transplantation.

  within 100 days following UCBT

Secondary Outcomes (5)

• The cumulative incidence and severity of pre-engraftment syndrome (PES)

  on day 28±7 following UCBT

• The cumulative incidence and grade of graft-versus-host disease (GVHD)

  within 1 year following UCBT

• The cumulative incidence of relapse

  within 1 year following UCBT

• Overall survival rate

  within 1 year following UCBT

• The cumulative incidence of adverse event

  within 1 year following UCBT

Study Arms (1)

40 patients with malignant hematological diseases who underwent UCBT

EXPERIMENTAL

Procedure: Umbilical Cord Blood Transplantation

Interventions

Umbilical Cord Blood Transplantation PROCEDURE

Compared with peripheral blood stem cell transplantation (PBST), UCBT has a higher transplantation rate, as cord blood stem cells are more primitive. Since the first successful umbilical cord blood transplantation (UCBT) in a child with severe Fanconi anemia reported by Gluckman et al. in France in 1988, cord blood has been widely used as a graft source of hematopoietic stem cells for the treatment of hematological diseases. The first sibling UCBT for leukemia was performed successfully by Professor Yongping Song in China, who played a pioneering role in the development of UCBT for leukemia in China. On the basis of previous research, the TFBC regimen (TBI/Flu/Bu/Cy) combined with UCBT is safe and feasible for the treatment of patients with high-risk malignant hematological diseases, which has enormous potential to improve patient outcomes.

Also known as: Total Body Irradiation/Fludarabine/Busulfan/Cyclophosphamide

40 patients with malignant hematological diseases who underwent UCBT

Eligibility Criteria

• Age: 14 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Gender is not limited, patients between 14 to 70 years old (including critical value);
• High-risk malignant hematological diseases (acute lymphoblastic leukemia, acute/chronic myeloid leukemia, multiple myeloma, etc.) diagnosed by bone marrow aspiration or biopsy according to the WHO diagnostic criteria;
• 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%);
• Umbilical cord blood with HLA match ≥ 4/6;
• Expected survival ≥3 months;
• Karnofsky (KPS) score ≥60%, Eastern Tumor Cooperative group (ECOG) status ≤ 2;
• Patient fully understood the nature of the study, and voluntarily participates and signs informed consent.

You may not qualify if:

• Patients had serious adverse reactions to investigational drugs such as allergies;
• Patients with a history of immunodeficiency, or other acquired or congenital diseases, immunodeficiency diseases, and a history of organ transplantation;
• 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;
• Two or more surgeries were performed within 4 weeks prior to enrollment;
• Patients with active viral infections, including HIV, HBV, HCV, TP;
• Pregnant or lactating patients;
• The patient is currently participating in another clinical studies;

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Study Sites (1)

The First Affiliated Hospital of Soochow university

Suzhou, Jiangsu, China

RECRUITING

Related Publications (15)

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MeSH Terms

Interventions

Cord Blood Stem Cell Transplantation; Whole-Body Irradiation

Intervention Hierarchy (Ancestors)

Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy; Investigative Techniques

Central Study Contacts

Xiaojin Wu

CONTACT

+8613057493105; wuxiaojin@suda.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2023
• First Posted: July 3, 2023
• Study Start: June 1, 2023
• Primary Completion: December 31, 2024
• Study Completion (Estimated): May 31, 2026
• Last Updated: July 6, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)