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Multi-center Trial for Children with B-cell NHL or B-AL: Evaluation of Rituximab Efficacy and Safety in High Risk Patients. (B-NHL-14)

Multi-center Trial for Children with B-cell NHL or B-AL: Evaluation of Rituximab Efficacy and Safety in High Risk Patients. (B-NHL-14)

45

From April 2016 through September 2018, a total of 45 patients were enrolled. The intention-to-treat population included all 45 patients. The median age was 8 years (range, 1 to 17 years), and 34 patients (75.6%) were male. Thirty-three patients (73.3%) had Burkitt's lymphoma, and 5 patients (11.1%) had diffuse large B-cell lymphoma. Ten patients (22.2%) had central nervous system disease, and 21 patients (46.7%) presented acute leukemia disease.

Eighteen (40.0%), 21(46.7%), and 5(11.1%) patients were assigned to the treatment group B, C1, and C3, respectively. One patient received only the prephase COP treatment because of a diagnosis of lymphoblastic lymphoma.

After the prephase COP treatment, the incidence of non-hematologic adverse events of grade 4 or higher was 5/44 (11.4%). The most common non-hematologic adverse events of grade 3 or higher after the prephase COP treatment was febrile neutropenia and its incidence was 24/45 (53.3%). During the study periods, 10 severe adverse events from 8 patients including infectious disease (3), reversible posterior leukoencephalopathy (2), tumor lysis syndrome, acute renal failure, consciousness disorder, gastrointestinal perforation, and abnormal laboratory value were reported. All above events were recovered.

The median follow-up was 47.5 months. Only one event was observed and it was relapse. Event-free survival at 3 years was 97.7% (95% confidence interval [CI], 84.9 to 99.7) . The lower limit of 80% CI was 92.1%, above the threshold of 75%. Overall survival at 3 years was 100%. All patients achieved complete remission by the final assessment time. The percentage of patients with a low IgG level at inclusion, at 1-3 months after end of treatment, and at 1 year after enrollment were 45.5%, 56.8%, and 45.5% respectively. Twenty of 44 patients (45.5%) received at least one dose of intravenous immune globulin. At one year after enrollment, one patient (2.2%) had a peripheral blood lymphocyte count <1,000/mm3.

Efficacy of rituximab added standard LMB chemotherapy for high-risk children with B-cell NHL or B-AL were confirmed in Japan. Compared with results of the international trial, the lower incidence of non-hematologic adverse events of grade 4 or higher, and the higher proportion of patients still receiving intravenous immune globulin at 1 year after enrollment were observed.

Jan. 31, 2024

Dec. 19, 2023

https://onlinelibrary.wiley.com/doi/10.1111/ejh.14148

No

https://jrct.mhlw.go.jp/latest-detail/jRCTs041180089

Mori Tetsuya

St. Marianna University School of Medicine

2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa

morite@marianna-u.ac.jp

Mori Tetsuya

St. Marianna University School of Medicine

2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa

+81-44-977-8111

morite@marianna-u.ac.jp

Complete

April. 01, 2016

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

(1) Histologically or cytologically proven B-cell malignancies, either Burkitt lymphoma or B-AL (=Burkitt leukaemia = L3-AL) or diffuse large B-cell NHL or aggressive mature B-cell NHL non other specified or specifiable.
(2) Stage III with elevated LDH level, (LDH > twice the institutional upper limit of the adult normal values) or any stage IV or B-AL.
(3) 6 months to less than 18 years of age at the time of consent.
(4) Males and females of reproductive potential must agree to use an effective contraceptive method during the treatment, and after the end of treatment: during twelve months for women, taking into account the characteristics of rituximab and during five months for men, taking into account the characteristics of methotrexate.
(5) Complete initial work-up within 8 days prior to treatment that allows definite staging.
(6) Able to comply with scheduled follow-up and with management of toxicity.
(7) Signed informed consent from patients and/or their parents or legal guardians.
(8) JPLSG-CHM-14 registration.

Histology and staging disease
(1)Follicular lymphoma, MALT and nodular marginal zone are not included into this therapeutic study - In phase II study (PMLBL) patients with CNS involvement are not eligible.

General conditions
(2) Patients with congenital immunodeficiency, chromosomal breakage syndrome, prior organ
transplantation, previous malignancy of any type, or known positive HIV serology.
(3) Evidence of pregnancy or lactation period.
(4) There will be no exclusion criteria based on organ function. Dosing guidelines for organ
dysfunction are provided in annexe D1.

Prior therapy
(5) Past or current anti-cancer treatment except corticosteroids of less than 7 days duration in total.

(6) Exclusion criteria related to rituximab
6-1)Tumor cell negative for CD20 (absence of result due to technical problems in the presence of other characteristics suggestive of BL/DLBCL, including genetic and phenotypic features, is not an exclusion criteria).
6-2) Prior exposure to rituximab.
6-3) Severe active viral infection, especially hepatitis B.
6-4) Severe infection (such as sepsis, pneumonia, etc.) should be clinically controlled at the time of registration. Contact the national co- investigator for further advice if necessary.
6-5) Hepatitis B carrier status history of HBV or positive serology. A patient is considered as HBV
carrier or to have (had) HBV infection in case of:
6-5-1) Unimmunized and HBsAg and/or anti-HBs antibody and/or anti- HBc antibody positive,
6-5-2)Immunized and HBsAG and/or anti-HBc antibody positive.

Others
(7) Participation in another investigational drug clinical trial.
(8) Patients who, for any reason, are not able to comply with the national legislation.

Both

B-cell NHL or Mature B-cell Acute Leukemia

The patients will receive a total of 6 injections of the antibody: 2 at 48h interval at D-2 and D1 of the 2 COPADM courses and one injection at D1 of the 2 consolidation courses either CYM (B) or CYVE (C1 or C3). Rituximab is given at the dose of 375 mg/m2 I.V.

Event free survival

1)Survival
2)Complete remission rate
3)Acute and long term toxicity
4)Immune reconstitution assessed by immunogloburin level and lymphocyte counts

+81-52-951-1111

Jan. 24, 2019

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