Allogeneic Hematopoietic Stem Cell Transplantation for 4/M Neuroblastoma

Summary

Neuroblastoma (NB) is the most common extracranial solid tumor of embryonal origin in children. According to the International Neuroblastoma Risk Group (INRG) staging criteria and the International Neuroblastoma Staging System (INSS) ，NB preoperative staging is divided into L1, L2, M and Ms stages, the postoperative staging is divided into 1 to 4 stages and 4s stage. Among them, 4/M stage is of the highest degree of malignancy and the worst prognosis. Despite the aggressive combination therapy, the 5-year survival rate (OS) is still less than 15%, and the 2-year relapse rate is 80%. Currently, no effective treatment is accessible for refractory/relapsed stage 4/M NB after completing conventional therapy.

In hematopoietic stem cell transplantation (HSCT) , conditioning regimen with high-dose radiotherapy and chemotherapy is implemented to eradicate tumor cells and abnormal clonal cells in the patient, block the pathogenesis, and restore the patient's hematopoietic and immune systems by transplanting normal hematopoietic stem cells. According to the source of hematopoietic stem cells, HSCT can be divided into two types: autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). It has been confirmed that benefiting from the graft versus tumor(GVT) effect, allo-HSCT can clear residual lesions in refractory/relapsed NB patients post-auto-HSCT，and prolong the survival time of patients. Our center has explored the conditioning regimen, treatment of residual tumor lesions before transplantation, and strategies to reduce transplantation-related death (TRM) and enhance the GVT effect. However, the sample size is small, and multicenter and larger sample size research are needed. This study will further observe the clinical efficacy and safety of allo-HSCT in the treatment of 4/M stage NB, and provide a new treatment method and option for 4/M stage NB.

Conditions

• Neuroblastoma

Interventions

DRUG

Anti Thymocyte Globulin

2.5 mg/kg/day；2 doses on day -3 and day -2 for matched sibling donor transplantation；3 doses on day -4，-3 and day -2 for unrelated donor transplantation；4 doses on day -5，-4，-3 and day -2 for haploidentical donor transplantation

DRUG

Fludarabine

30 mg/m2/day for 5 days

DRUG

Cyclophosphamide injection

60 mg/kg/day for 2 days in cord blood stem cell transplantation

DRUG

Topotecan

2mg/m2/day for 3 days in cord blood stem cell transplantation

DRUG

Melphalan

70mg/m2/day，for peripheral stem cell transplantation or haploidentical bone marrow combined with peripheral stem cell transplantation；2 doses on day -3 and day -2 when conditioning regimen containing thiotepa；3 doses on day -4，-3 and day -2 when conditioning regimen not containing thiotepa；

DRUG

Thiotepa

5 mg/kg/day for 2 days in peripheral stem cell transplantation or haploidentical bone marrow combined with peripheral stem cell transplantation

DRUG

Busulfan

0.8mg/kg/dose；8 doses in cord blood stem cell transplantation；12 doses in peripheral stem cell transplantation or haploidentical bone marrow combined with peripheral stem cell transplantation when conditioning regimen containing thiotepa；16 doses in peripheral stem cell transplantation or haploidentical bone marrow combined with peripheral stem cell transplantation when conditioning regimen not containing thiotepa；

DRUG

Cyclosporine

2.5\~4 mg/kg/dose every 12 hours orally；1.5\~2 mg /kg/dose every 12 hours intravenously; trough concentration maintained at 150\~250ng/ml

DRUG

Tacrolimus

0.02\~0.03 mg/kg/day as continuous infusion or 12 hour divided doses

DRUG

Mycophenolate Mofetil

15 mg/kg/dose every 12 hours

DRUG

Methotrexate

15 mg/m2/dose on d+1 and 10 mg/m2/dose on d+3，d+6 in peripheral stem cell transplantation

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  lead OTHER

Principal Investigators

• Yang Li · Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

• Jianpei Fang · Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-08-31

Primary Completion

2027-08-31

Completion

2027-08-31

Countries

• China

Study Locations