Phase I clinical study of brentuximab vedotin (SGN-35) involving children with recurrent or refractory CD30-positive Hodgkin\u2019s lymphoma or systemic anaplastic large cell lymphoma: rationale, design and methods of BV-HLALCL study: study protocol

Masahiro Sekimizu,Keizo Horibe,Akiko Kada,Yuhki Koga,Akihiro Iguchi,Tetsuya Mori,Akiko M Saito

doi:10.1186/s12885-018-4042-1

Abstract

BackgroundHodgkin’s lymphoma (HL) and anaplastic large-cell lymphoma (ALCL) are the two most common tumors expressing CD30. Internationally, a clinical study that is being conducted involving adults with recurrent or refractory HL or ALCL suggests efficacy of brentuximab vedotin (SGN-35). Pediatric patients should be given medicines that have been appropriately evaluated for their use. In the past, however, new approved drugs have been used for pediatric patients without the confirmation of safety and efficacy in pediatric patients. Therefore, it is important to examine the safety and efficacy of SGN-35 in Japanese children.MethodsPhase I clinical study of SGN-35 involving children with recurrent or refractory CD30-positive Hodgkin’s lymphoma or systemic anaplastic large cell lymphoma (BV-HLALCL study) is being conducted for pediatric patients in order to evaluate the safety, feasibility and preliminary clinical effectiveness of brentuximab vedotin. SGN-35 is intravenously administered on Day 1 of each cycle (21 days/cycle). The dose of SGN-35 is calculated based on the body weight at the baseline. The primary endpoint is dose limiting toxicity and incidence of adverse events. The secondary endpoints are pharmacokinetics, response rate, complete remission rate, response duration, progression-free survival and event-free survival. The reduction rate of tumor will be calculated according to revised response criteria for malignant lymphoma for measurable tumor. Six pediatric patients will be enrolled in this study.DiscussionThis study aims to expand indication of SGN-35 in Japan by assessing its safety and efficacy in pediatric patients.Trial registrationJMACCT ID: JMA-IIA00229. Registered on 17 Nov 2015.

Highlights

Hodgkin’s lymphoma (HL) and anaplastic large-cell lymphoma (ALCL) are the two most common tumors expressing CD30
The treatment of HL and ALCL has largely relied on cytotoxic chemotherapy
Basic treatment for childhood HL consists of chemotherapy and low-dose involved field radiotherapy (LD-IFRT)

Summary

Introduction

Hodgkin’s lymphoma (HL) and anaplastic large-cell lymphoma (ALCL) are the two most common tumors expressing CD30. Basic treatment for childhood HL consists of chemotherapy and low-dose involved field radiotherapy (LD-IFRT). Chemotherapy alone or a combination of chemotherapy and LD-IFRT is selected in accordance with individual children. In Japan, treatment has not been standardized, and is selected based on the results of international clinical studies in accordance with individual patients. In a representative clinical study regarding childhood HL, the GPOH-HD-2002 study, chemotherapy with vincristine, etoposide, prednisolone, doxorubicin, cyclophosphamide, and procarbazine and LD-IFRT for some patients improved the 5-year eventfree survival rate to 89%, and the 5-year survival rate to 97% [1]. Patients with local relapse after initial treatment for a low-risk group may be saved by chemotherapy and LD-IFRT, but the exacerbation-free survival rate ranges from 30 to 65% in other patients with treatment resistance/relapse even when hematopoietic cell transplantation is performed [2, 3]

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