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Clinical study of bleomycin and OK-432 combined local injection sclerotherapy for intractable lymphatic malformations

Study of bleomycin and OK-432 combined scletotherapy for LMs

29

The subjects were "patients treated at the National Center for Child Health and Development with a diagnosis of lymphangioma (lymphangitic malformation, general or cystic type lymphangitic malformation) and diseases with similar tissue requiring treatment," regardless of age or gender. Among the above-mentioned subjects, intractable patients who fulfilled the following conditions A and B, and who understood and agreed to the written explanation. A, The patient meets either of the following (1) or (2). (1) Patients with residual cavernous lesions after previous OK-432 treatments. (2) Cavernous lesion untreated with OK-432 sclerotherapy, however, likely to be ineffective for. B, Inappropriate for surgical resection. Under these conditions, 12 male and 17 female patients between the ages of 0 and 14 years were included in the study.

Patients included were 12 cases in 2016, 11 in 2017, 6 in 2018, 29 in total cases. Patients completed were 4 cases in 2017, 0 cases in 2018, 10 cases in 2019, 4 cases in 2020, 1 case in 2021, 2 cases in 2022, 21 in total cases. The other 8 cases withdrew during the course of the study. The reasons for withdrawal were: difficulty in continuing due to relocation (1 domestic, 1 overseas), transfer to other hospital (1 case), transfer to other treatment methods (4 cases), and termination by request (1 case). Due to the high number of withdrawals from the study, the number of entries exceeded the planned number, and the study was ultimately terminated at the target number. Of the 21 patients, 20 had cystic lymphatic malformation and 1 had Klippel-Trenaunay syndrome.

Of the 29 patients, the following adverse events were observed. Hardening of the lesion (7), pigmentation (6), lymphatic leakage (1), internal bleeding (2), and blistering (1), but there was no occurrence of pulmonary fibrosis, a known serious adverse event that was feared with bleomycin. No patient reached the prescribed limit of use, and the potential risk have been avoided as planned.

The primary endpoint, "the percentage of subjects with a volume reduction of 30% or greater in the target area of treatment within the lesion," was 52% in 11 of 21 patients. Secondary endpoints showed no change in lung field shadows on chest radiographs in all patients. The degree of appearance and elevation was difficult to assess objectively by photography. Clinical manifestations (adverse events), such as lymph leakage and hemorrhage, were described in the adverse events section (see above), and subjects were satisfied with the degree of improvement with treatment in 12 cases, generally consistent with a volume reduction of 30% or more.

The "clinical study of combination local injection sclerotherapy of bleomycin and OK-432 for intractable lymphatic malformations" demonstrated that this therapy is safe and effective in reducing lesion volume in more than half of patients with refractory disease who have difficulty improving with current therapies. There are no studies in the world that have examined the efficacy and safety of bleomycin in refractory cases from an anteroposterior viewpoint, and the results are extremely significant.

Mar. 31, 2023

No

No plans.

https://jrct.mhlw.go.jp/latest-detail/jRCTs031180265

Fujino Akihiro

National Center for Child Health and Development

2-10-1 Okura, Setagaya-Ku, Tokyo

fujino-a@ncchd.go.jp

Fujino Akihiro

National Center for Child Health and Development

2-10-1 Okura, Setagaya-Ku, Tokyo

+81-3-3416-0181

fujino-a@ncchd.go.jp

Complete

Aug. 10, 2016

Interventional

single arm study

open(masking not used)

no treatment control/standard of care control

single assignment

treatment purpose

Patients requiring treatment in the National Center for Child Health and Development, diagnosed as lymphangioma (lymphatic malformation, common and cystic lymphatic malformation) or other lymphatic disease with similar pathological tissue.
Among the above-mentioned subject, patients satisfying the following conditions A and B, and having understood and agreed to the research by document, will be included.
Condition A; satisfying the following condition a or b.
a; spongy lesions remaining after the OK-432 therapy in the past
b; spongy lesion untreated with sclerotherapy and expected of no efficacy of OK-432
Condition B; surgical resection is difficult to apply.

Patients with any of the following diseases will be excluded.
Severe lung dysfunction, lung fibrosis lesions and significant lung lesions, history of hypersensitivity to bleomycin hydrochloride and similar compounds to the (peplomycin), severe renal dysfunction, severe heart disease, and history of radiation to the chest and the periphery.

Both

Lymphangioma (lymphatic malformation, common or cystic lymphatic malformation), and other lymphatic

"OK-432 and bleomycin slolution" (0.05 kE / mL and 0.5 mg / mL, respectively) will be injected into the lesion with water-soluble contrast agent Maximum dose of bleomycin is 10 mg /dose and 5 mg/kgBW.Cumulative maximum dose in repeated treatment is 10 mg/kgBW

lymphangioma, lymphatic malformation,

Bleomycin, OK-432, sclerotherapy

D18.1

The proportion of subjects that the volume of therapeutic target area in the lesion is reduced 30% or more

Appearance, degree of uplift due to lesions, clinical symptoms such as lymph leakage and bleeding, pain, and frequency of fever / redness,the subjects' impression of their improvement and their degree of satisfaction. Changes in the lung shadows on chest X-ray.

+81-3-3416-0181

Feb. 26, 2019

none