Allogeneic Hematopoietic Stem Cell Transplantation for 4/M Neuroblastoma

Phase 2

Not yet recruiting

• Conditions: Neuroblastoma
• Interventions: Drug: Anti Thymocyte Globulin; Drug: Fludarabine; Drug: Cyclophosphamide injection; Drug: Topotecan; Drug: Melphalan; Drug: Thiotepa; Drug: Busulfan; Drug: Cyclosporine; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Drug: Methotrexate

• Registration Number: NCT05303727
• Lead Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Brief 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 ...

Detailed Description

Purposes: To evaluate the efficacy and safety of allo-HSCT in children with stage 4/M high-risk NB through a multi-center prospective single-arm clinical research grouped according to different types of donors, graft sources, and stratified conditioning regimen.
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Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Status Verified: 2022-03
• Study First Submitted: 2022-03-16
• Study First Submitted QC: 2022-03-27
• Study First Posted: 2022-03-31
• Last Update Submitted: 2022-06-29
• Last Update Posted: 2022-07-01
• Study Start: 2022-08
• Primary Completion: 2027-08
• Study Completion: 2027-08

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

one of the following criteria (2), (3) or (4) must be met and all other criterions must be met at the same time:

1. Age≤18 years old;

2. After at least 7 courses of induction chemotherapy (surgical resection of the primary tumor or metastatic disease has been completed during the period), evaluation of disease is CR, tumor markers (blood NSE and urine VMA) and minimal residual disease by flow cytometry of bone marrow and peripheral blood are negative; the primary tumor has completed radiotherapy before HSCT;

3. For patients with PR or VGPR, tumor markers (blood NSE and urine VMA) and minimal residual disease by flow cytometry of bone marrow and peripheral blood are negative; the primary tumor and metastatic lesions have completed radiotherapy before HSCT;

4. Relapsed patients achieve CR/VGPR/PR after re-induction or salvage chemotherapy, tumor markers (blood NSE and urine VMA) and minimal residual disease by flow cytometry of bone marrow and peripheral blood are negative; the primary tumor and metastatic lesions have completed radiotherapy before HSCT;

5. Whole brain and whole spinal cord radiotherapy have completed before HSCT in patients with central invasion at onset;

6. The blood routine has generally returned to normal and there is no dysfunction of major organs such as the heart, liver, lung, and kidney;

7. The guardian/patient accept the treatment of this research, sign the informed consent, and complete the follow-up.

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Exclusion Criteria

meeting one of the following criterions:

1. With severe cardiac insufficiency, cardiac ejection fraction (EF) is less than 50%; or severe cardiac disease, the patient can not tolerate the conditioning regimen according to the investigators' evaluation;
2. With severe pulmonary insufficiency (severe obstructive and/or restrictive ventilation disorders), the patient can not tolerate the conditioning regimen according to the investigators' evaluation;
3. With severe liver function impairment, ALT>5 times upper limit of normal, or total bilirubin>3 times upper limit of normal; the patient can not tolerate the conditioning regimen according to the investigators' evaluation;
4. With severe renal insufficiency, creatinine>2 times upper limit of normal; or corrected creatinine clearance rate Ccr<50ml/min; the patient can not tolerate the conditioning regimen according to the investigators' evaluation;
5. With severe active bleeding or severe active infection; the patient can not tolerate the conditioning regimen according to the investigators' evaluation;
6. Allergic reactions or serious adverse reactions occurred in the previous use of conditioning regimen-related drugs, the patient can not tolerate the conditioning regimen according to the investigators' evaluation;
7. The guardian/patient cannot understand or comply with the treatment plan;
8. Other reasons for not being selected due to the investigator's evaluation.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Conditioning regimen for different sources of donors	Anti Thymocyte Globulin	There are 3 groups according to different sources of donor: (1) Cord blood HSCT: Flu+Bu+CTX+Topotecan (without ATG); (2) Peripheral blood HSCT or haploid bone marrow combined with peripheral stem cell transplantation: Flu+Bu+Melphalan+Antithymocyte globulin (ATG)+ Thiotepa (TT) or (3) Flu+Bu+Melphalan+ATG (applicable to peripheral stem cells or haploid bone marrow combined with peripheral stem cell transplantation for which TT cannot be used).
Conditioning regimen for different sources of donors	Cyclophosphamide injection	There are 3 groups according to different sources of donor: (1) Cord blood HSCT: Flu+Bu+CTX+Topotecan (without ATG); (2) Peripheral blood HSCT or haploid bone marrow combined with peripheral stem cell transplantation: Flu+Bu+Melphalan+Antithymocyte globulin (ATG)+ Thiotepa (TT) or (3) Flu+Bu+Melphalan+ATG (applicable to peripheral stem cells or haploid bone marrow combined with peripheral stem cell transplantation for which TT cannot be used).
Conditioning regimen for different sources of donors	Mycophenolate Mofetil	There are 3 groups according to different sources of donor: (1) Cord blood HSCT: Flu+Bu+CTX+Topotecan (without ATG); (2) Peripheral blood HSCT or haploid bone marrow combined with peripheral stem cell transplantation: Flu+Bu+Melphalan+Antithymocyte globulin (ATG)+ Thiotepa (TT) or (3) Flu+Bu+Melphalan+ATG (applicable to peripheral stem cells or haploid bone marrow combined with peripheral stem cell transplantation for which TT cannot be used).
Conditioning regimen for different sources of donors	Fludarabine	There are 3 groups according to different sources of donor: (1) Cord blood HSCT: Flu+Bu+CTX+Topotecan (without ATG); (2) Peripheral blood HSCT or haploid bone marrow combined with peripheral stem cell transplantation: Flu+Bu+Melphalan+Antithymocyte globulin (ATG)+ Thiotepa (TT) or (3) Flu+Bu+Melphalan+ATG (applicable to peripheral stem cells or haploid bone marrow combined with peripheral stem cell transplantation for which TT cannot be used).
Conditioning regimen for different sources of donors	Busulfan	There are 3 groups according to different sources of donor: (1) Cord blood HSCT: Flu+Bu+CTX+Topotecan (without ATG); (2) Peripheral blood HSCT or haploid bone marrow combined with peripheral stem cell transplantation: Flu+Bu+Melphalan+Antithymocyte globulin (ATG)+ Thiotepa (TT) or (3) Flu+Bu+Melphalan+ATG (applicable to peripheral stem cells or haploid bone marrow combined with peripheral stem cell transplantation for which TT cannot be used).
Conditioning regimen for different sources of donors	Melphalan	There are 3 groups according to different sources of donor: (1) Cord blood HSCT: Flu+Bu+CTX+Topotecan (without ATG); (2) Peripheral blood HSCT or haploid bone marrow combined with peripheral stem cell transplantation: Flu+Bu+Melphalan+Antithymocyte globulin (ATG)+ Thiotepa (TT) or (3) Flu+Bu+Melphalan+ATG (applicable to peripheral stem cells or haploid bone marrow combined with peripheral stem cell transplantation for which TT cannot be used).
Conditioning regimen for different sources of donors	Topotecan	There are 3 groups according to different sources of donor: (1) Cord blood HSCT: Flu+Bu+CTX+Topotecan (without ATG); (2) Peripheral blood HSCT or haploid bone marrow combined with peripheral stem cell transplantation: Flu+Bu+Melphalan+Antithymocyte globulin (ATG)+ Thiotepa (TT) or (3) Flu+Bu+Melphalan+ATG (applicable to peripheral stem cells or haploid bone marrow combined with peripheral stem cell transplantation for which TT cannot be used).
Conditioning regimen for different sources of donors	Cyclosporine	There are 3 groups according to different sources of donor: (1) Cord blood HSCT: Flu+Bu+CTX+Topotecan (without ATG); (2) Peripheral blood HSCT or haploid bone marrow combined with peripheral stem cell transplantation: Flu+Bu+Melphalan+Antithymocyte globulin (ATG)+ Thiotepa (TT) or (3) Flu+Bu+Melphalan+ATG (applicable to peripheral stem cells or haploid bone marrow combined with peripheral stem cell transplantation for which TT cannot be used).
Conditioning regimen for different sources of donors	Thiotepa	There are 3 groups according to different sources of donor: (1) Cord blood HSCT: Flu+Bu+CTX+Topotecan (without ATG); (2) Peripheral blood HSCT or haploid bone marrow combined with peripheral stem cell transplantation: Flu+Bu+Melphalan+Antithymocyte globulin (ATG)+ Thiotepa (TT) or (3) Flu+Bu+Melphalan+ATG (applicable to peripheral stem cells or haploid bone marrow combined with peripheral stem cell transplantation for which TT cannot be used).
Conditioning regimen for different sources of donors	Tacrolimus	There are 3 groups according to different sources of donor: (1) Cord blood HSCT: Flu+Bu+CTX+Topotecan (without ATG); (2) Peripheral blood HSCT or haploid bone marrow combined with peripheral stem cell transplantation: Flu+Bu+Melphalan+Antithymocyte globulin (ATG)+ Thiotepa (TT) or (3) Flu+Bu+Melphalan+ATG (applicable to peripheral stem cells or haploid bone marrow combined with peripheral stem cell transplantation for which TT cannot be used).
Conditioning regimen for different sources of donors	Methotrexate	There are 3 groups according to different sources of donor: (1) Cord blood HSCT: Flu+Bu+CTX+Topotecan (without ATG); (2) Peripheral blood HSCT or haploid bone marrow combined with peripheral stem cell transplantation: Flu+Bu+Melphalan+Antithymocyte globulin (ATG)+ Thiotepa (TT) or (3) Flu+Bu+Melphalan+ATG (applicable to peripheral stem cells or haploid bone marrow combined with peripheral stem cell transplantation for which TT cannot be used).

Primary Outcome Measures

Name	Time	Method
overall survival(OS) at 3 year	3 years post-HSCT	From the date of day 0 of transplantation until the date of death from any cause
event free survival(EFS) at 3 year	3 years post-HSCT	Survival time from day 0 of transplantation to the occurrence of the first adverse event. Disease or treatment-related adverse events, such as tumor recurrence, implant failure, and death, are counted in this study; accidental deaths that assessed unrelated to the above factors are not included

Secondary Outcome Measures

Name	Time	Method
incidence of transplant associated thrombotic microangiopathy(TA-TMA)	3 years post-HSCT	TA-TMA is diagnosed according to the Jodele standard.
incidence of donor engraftment	100 days post-HSCT	Donor engraftment represents donor cells replace at least 95% of recipient hematopoietic stem cells.
early transplant-related mortality	100 days post-HSCT	Death due to transplantation, excluding other causes such as disease progression or relapse.
incidence of infection	3 years post-HSCT	e.g. EBV/CMV viremia or related disease, bacteria/fungi /tuberculosis infection
incidence of conditioning toxicity	100 days post-HSCT	Conditioning toxicity is graded according to the Common Terminology Criteria for Adverse Events(CTCAE Version 5.0)
incidence of sinusoidal obstruction syndrome	3 years post-HSCT	Sinusoidal obstruction syndrome is diagnosed according to classification from the European society for blood and marrow transplantation.
incidence of acute graft versus host disease	100 days post-HSCT	Acute graft versus host disease is diagnosed according to the modified Glucksberg grading standard.
incidence of chronic graft versus host disease	3 years post-HSCT	Chronic graft versus host disease is diagnosed according to the grading and scoring system recommended by the "Chinese Consensus on the Diagnosis and management of Chronic Graft-versus-Host Disease(2021)".

Trial Locations

Locations (1)

Sun Yat-sen Memorial Hospital, Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China