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Feasibility of high-dose iodine-131-metaiodobenzylguanidine therapy for high-risk neuroblastoma preceding myeloablative chemotherapy and hematopoietic stem cell transplantation (High-dose iodine-131-metaiodobenzylguanidine therapy for high-risk neuroblastoma)

High-dose I-131-MIBG therapy for high-risk neuroblastoma preceding myeloablative chemotherapy and hematopoietic stem cell transplantation (High-dose iodine-131-metaiodobenzylguanidine therapy for high-risk neuroblastoma)

8

Primary and relapsed high-risk neuroblastoma

Single-center, uncontrolled, open-label study

No dose-limiting toxicity was observed in all 8 treated patients. The major adverse events, graded based on CTCAE 4.0 criteria, were diarrhea, myelosuppression, loss of appetite, fever, vomiting, fatigue, febrile neutropenia, nausea, and abdominal pain during the entire study period. The main adverse reactions, graded based on CTCAE 4.0 criteria, were myelosuppression and anorexia. There were no deaths. Only one serious adverse event, the catheter breakage, occurred. But a causal relationship with the study drug was ruled out. We reported it as a serious adverse event due to the prolonged hospital stay for replacement. As major adverse events (same as adverse reactions) due to 131I-MIBG therapy, anorexia and myelosuppression were observed. With the high-dose chemotherapy, vomiting, fatigue, and nausea were observed as major adverse events. Epistaxis was observed as a major adverse event after the study treatment.

Primary Endopoint: No dose-limiting toxicity was observed in all 8 treated patients. Secondary Endopoint: 1) Safety evaluation: During the entire study period, the major adverse events were diarrhea, myelosuppression, loss of appetite, fever, vomiting, fatigue, febrile neutropenia, nausea, and abdominal pain. The main adverse reactions were myelosuppression and anorexia. There were no deaths. Only one serious adverse event, the catheter breakage, occurred. But a causal relationship with the study drug was ruled out. As major adverse events due to 131I-MIBG therapy, anorexia and myelosuppression were observed. With the high-dose chemotherapy, vomiting, fatigue, and nausea were observed as major adverse events. Epistaxis was observed as a major adverse event after the study treatment. Response evaluation: 2) Hematopoietic stem cell transplantation was performed, and the engraftment was confirmed in all registered cases. The effect evaluation based on RECIST was SD 87.5%, NE 12.5%, and the response rate was 0.0% (95% CI: 0.0 - 36.9%). The effect evaluation by MIBG scintigraphy was CR of 62.5%, SD of 37.5%, and the response rate of 62.5% (95%CI: 24.5 - 91.5%). The median overall survival could not be calculated due to no death event within 4 weeks of a haematopoietic stem cell transplant (years since registration, median 1.6 yr). The median progression-free survival could not be calculated due to no event within 4 weeks of a haematopoietic stem cell transplant (days since registration, median 59.5 d).

The aim of this study is to evaluate the safety, dose-limiting toxicity (DLT), and efficacy of 131I-MIBG therapy combined with myeloablative high-dose chemotherapy and hematopoietic stem cell transplantation in patients with high-risk neuroblastoma. None experienced DLT that hinder subsequent high-dose chemotherapy initiation due to 131I-MIBG therapy. The safety of 131I-MIBG therapy was shown. The response rate was 0% based on RECIST and 63% based on MIBG scintigraphy.

Nov. 10, 2021

No

No

https://jrct.niph.go.jp/latest-detail/jRCTs041180030

Wakabayashi Hiroshi

Kanazawa University Hospital

Takaramachi 13-1, Kanazawa, Ishikawa, 920-8641, Japan

wakabayashi@staff.kanazawa-u.ac.jp

Kuroda Rie

Kanazawa University Hospital

Takaramachi 13-1, Kanazawa, Ishikawa, 920-8641, Japan

+81-76-265-2313

pedkuro@staff.kanazawa-u.ac.jp

Complete

July. 01, 2017

Interventional

single arm study

open(masking not used)

no treatment control/standard of care control

single assignment

treatment purpose

1) have a definitive diagnosis of neuroblastoma.
2) have high-risk neuroblastoma.
3) have one or more 123I-MIBG-avid lesion at initial presentation or relapse.
4) have enough cryopreserved autologous peripheral blood stem cells, cord blood, or other stem cell cource.
5) meet the following criteria:
5)-1 bone marrow function
1 Neutrophils >=500/microL
2 Platelets >=20x10E3/microL, and transfusion independent
3 Hb >=7.0g/dL
5)-2 Renal function
Serum Cr <=0.8mg/dL(<5year), 1.2mg/dL(5-9year), 1.5mg/dL(10-17year)
Creatinine clearance >=70mL/min/1.73m2
5)-3 Liver function
1 ALT <= 5 x upper limit of normal for age
2 AST <= 5 x upper limit of normal for age
3 T. Bil <= 3 x upper limit of normal for age
5)-4 Cardiac function
NYHA classification class I or below
5)-5 Lung function
SpO2 >=94%
6) ECOG PS 0 or 1
7) be able to cooperate with the radiation safety isolation
8) written informed consent by patients or guardian

1) active double cancer
2) diffuse bone marrow involvement on a 123I-MIBG scan
3) Progressive disease
4) HBV (or carrier), HCV, HIV, or other active infections
5) history of fatal arrhythmia or asystole
6) concurrent poorly-controlled symptomatic arrhythmia, thyroid dysfunction, respiratory disorder, pleural effusion, or ascites.
7) concurrent coronary artery disease, usage of amiodarone, severe cardiac valvulopathy, aortic disease, or bleeding tendency.
8) woman during pregnancy or lactation, within the 28 postpartum day, desiring pregnancy within 1 year.
9) concurrent poorly-controlled psychiatric disorder
10) allergy to potassium iodide.
11) difficult to cooperate with the radiation safety isolation.
12) concurrent palliative external radiotherapy to painful lesions.
13) past treatment by the same regimen as this study.
14) be unable to receive at least of 444MBq/kg of MIBG due to exceeding of upper limit of radiation use at the center. As the upper limit of our center is 24,000MBq, the patient over 54kg is excluded.
15) Patients who, in the opinion of the attending physician, may not be able to comply with the requirements of the study.

Both

Neuroblastoma

All patients receive 131I-MIBG at 666 MBq/kg.
Subsequently, patients receive high-dose chemotherapy and hematopoietic stem cell transplantation.
The recommended regimen is MEC regimen consisting of melphalan, etoposide, and carboplatin, or BuMel regimen consisting of busulifan and melphalan.
Another regimen is acceptable depending on patient's condition.

High-risk neuroblastoma, 131I-MIBG therapy

D009447

Dose Limiting Toxicity: DLT

Incidence and type of adverse events
Hematopoietic stem cell engraftment rate
Response rate according to the Response Evaluation Criteria in Solid Tumors (RECIST) and 123I-MIBG scintigraphy
Overall survival
Progression-free survival.

+81-76-265-2048

none