臨床研究等提出・公開システム

A Multi-Center Phase II Study in Children with Newly Diag nosed Acute
Promyelocytic Leukemia (APL) (AML-P13)

AML-P13 (AML-P13)

32

Among 32 patients registered, 5 patients were excluded due to; died before treatment in 1 patient, errors in registration in 1 patient, and misdiagnosis in 3 patients, and remaining 27 patients were defined as full analysis set (FAS). Baseline characteristics of 27 FAS patients were as follows; age at diagnosis: 0.7 - 17.7 years (median: 12.7 years), leukocyte count: 1,290 - 144,400/microL (median 5,100/microL), platelet count: 4,000 - 172,000/microL (median: 29,000/microL).

Among 27 FAS patients, 2 patients ceased protocol study during remission induction courses due to lack of efficacy in 1 patient and prolonged bone marrow suppression in 1 patient. Among 25 patients who completed remission induction therapy, 2 patients did not obtain complete hematological remission and were allocated to high risk group (HRG) and received HRG intensification and maintenance therapy. Remaining 23 patients were allocated to standard risk group (SRG) and received SRG intensification and maintenance therapy. All 25 patients obtained molecular complete remission at the end of intensification therapy, and all patients including 2 patients who ceased protocol study are alive and well.

There were no severe adverse events (AE) which required immediate report throughout the study period. During remission induction courses, disseminated intravascular coagulation was reported in 12 patients as grade 2 and higher, and 9 patients as grade 3 and higher. APL differentiation syndrome and induction death were not observed during remission induction courses . Regarding arsenic trioxide (ATO)-related toxicity, equal or more than grade 3 non-hematological adverse events were observed in 3; 2 events for prolonged QTc interval and 1 event for dysesthesia. Regarding other AEs, 8 events in 6 patients were reported; elevated AST in 2, elevated ALT in 3, hypercalcemia in 1, pancreatitis in 1, and dysarthria in 1.

Three-year event-free survival (EFS) rate defined as primary endpoint was 96.3% [95% C.I. 76.5-99.5%] which exceeded designated threshold survival rate of 65%. Molecular remission rate at the end of intensification therapy and 3-year overall survival (OS) rate was 100.0% [95% C.I. 86.3-100.0%] and 100.0% [95% C.I. 87.2-100.0%], respectively.

Three-year EFS rate in the JPLSG AML-P13 study was 96.3%. Molecular remission rate and 3-year OS rate was 100.0% and 100.0%, respectively, indicating favorable outcome in patients registered with this study. ATO-related grade 3 and higher non-hematological AEs were observed only in 3. Hence, ATO could be administered safely in children with APL. In conclusion, AML-P13 study conferred favorable outcome in children with APL and provided substantial findings especially in safety and efficacy of ATO.

Mar. 17, 2022

Yes

The Japan Children's Cancer Group (JCCG) is committed to sharing, with qualified external researchers, access to patient-level data and supporting clinical documents from the eligible studies. These requests are reviewed and approved by the JCCG steering committee based on scientific merit. ALL data are anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

https://jrct.mhlw.go.jp/latest-detail/jRCTs051180191

TAKAHASHI Hiroyuki

Toho University Omori Medical Center

6-11-1 Omorinishi, Ota-ku, Tokyo 143-8451

hiroyuki.takahashi@med.toho-u.ac.jp

TAKAHASHI Hiroyuki

Toho University Omori Medical Center

6-11-1 Omorinishi, Ota-ku, Tokyo 143-8451

+81-3-3762-4151

hiroyuki.takahashi@med.toho-u.ac.jp

Complete

Dec. 01, 2014

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

Patient with a diagnosis of APL genetically or cytogenetically diagnosed by either one of three methods; karyotyping, FISH, or RT-PCR.
ECOG performance status score of 0-2, or of 3 when caused by leukemia.
No previous treatment.
Written informed consent obtained either from patient or guardians.

17q12/RARA not detected genetically and cytogenetically
APL with t(11;17)(q23;q12)/PLZF-RARA
CNS hemorrhage which is likely to interfere protocol therapy
Secondary APL due to previous chemotherapy or radiation therapy
Unmanageable infectious disease including tuberculosis
Any inappropriate status judged by physician

Both

Acute promyelocytic leukemia

To evaluate an efficacy and safety of the treatment strategy consisted of 2 courses of multi-agent chemotherapy followed by 3 courses of consolidation therapy with either ATO and/or GO.

Three-year event-free survival rate

Remission induction rate
Molecular remission rate at the end of consolidation therapy
Three-year overall survival rate
Rate of DIC, APL-DS, and mortality during first remission induction therapy
Rate of adverse events during ATO therapy
Rate of adverse events

+81-75-753-4680

Mar. 04, 2019

none