이 페이지는 자동 번역되었으며 번역의 정확성을 보장하지 않습니다. 참조하십시오 영문판 원본 텍스트의 경우.

소아 만성 골수성 백혈병 환자에서 Asciminib의 용량 및 안전성을 결정하기 위한 연구

2026년 11월 6일 업데이트: Novartis Pharmaceuticals

만성기의 필라델피아 염색체 양성 만성 골수성 백혈병(Ph+ CML-CP) 소아 환자에서 이전에 하나 이상의 티로신 키나제 억제제로 치료받은 적이 있는 경구 Asciminib의 용량 및 안전성을 결정하기 위한 다기관 공개 라벨 연구

The aim of this study is to support development of asciminib in the pediatric population (1 to <18 years) previously treated with one or more TKIs. Full extrapolation of the efficacy of asciminib from adult to pediatric patients will be conducted. Full extrapolation is based on the concept that CML in the pediatric population has the same pathogenesis, similar clinical characteristics and progression pattern as in adults.

연구 개요

상태

모집하지 않고 적극적으로

정황

개입 / 치료

상세 설명

The aim of this study is to support development of asciminib in the pediatric population (1 to <18 years) with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase (PH+ CML-CP) previously treated with one or more Tyrosine kinase inhibitor (TKIs).

The primary objective of this study is to characterize the pharmacokinetic (PK) profile of asciminib in pediatric patients with the goal of identifying the pediatric formulation dose (fed) leading to asciminib exposure comparable to 40 mg BID in adult patients (fasted).

The pediatric formulation group will include at least 15 participants in each of the following two age categories: 1 to <12 years and 12 to <18 years; leading to at least 30 participants enrolled treated with the pediatric formulation. It will consist of a dose determination part (Part 1) and a cohort expansion (Part 2 BID regimen and Part 3 QD regimen).

In Part 1, 4-6 participants will be enrolled in order to obtain at least 4 participants evaluable for PK (these participants may be from either of the age categories described above). The initial starting dose will be based on body weight and will be administered BID with food.

Once the body weight adjusted dose has been determined in Part 1 of the study, the patients will be enrolled in Part 2 until at least 20 participants, including those who were included in Part 1, have been enrolled (10 per age group) in the pediatric formulation group. Once the interim safety and PK analysis 2 is completed for one of the age groups, the Part 3 QD regimen will open for the respective age group to enroll 10 patients (5 patients by age group).

Due to the fact that the pediatric formulation was in development and was not available, this study started with the recruitment of adolescent patients. These participants aged 14 to <18 years, weighing at least 40 kg receive the adult formulation at a flat dose of 40 mg BID under fasted conditions.

The total duration of the treatment period of the study will be 5 years (260 weeks). Participants who, according to Investigator's judgement, are benefiting from study treatment will remain on treatment up to the completion of the treatment period (Week 260/5 years).

The primary analysis for the BID regimen is planned after all participants in Part 1 and 2 have completed at least 52 weeks of study treatment or discontinued earlier.

The primary analysis for combined regimen (BID+QD) is planned after all participants in Part 1, 2 and 3 have completed at least 52 weeks of study treatment or discontinued earlier.

연구 유형

중재적

등록 (실제)

46

단계

  • 2 단계
  • 1단계

확장된 액세스

사용 가능 임상시험 외. 확장 액세스 기록을 참조하세요.

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

  • 그리스
      • Athens, 그리스, 115 27
        • Novartis Investigative Site
  • 네덜란드
      • Utrecht, 네덜란드, 3584 CS
        • Novartis Investigative Site
  • 대한민국
      • Seoul, 대한민국, 03080
        • Novartis Investigative Site
      • Seoul, 대한민국, 05505
        • Novartis Investigative Site
  • 독일
      • Erlangen, 독일, 91054
        • Novartis Investigative Site
      • Essen, 독일, 45147
        • Novartis Investigative Site
      • Hamburg, 독일, 20246
        • Novartis Investigative Site
  • 미국
    • Indiana
      • Indianapolis, Indiana, 미국, 46202-5167
        • Indiana UH Riley H for CIU
    • Massachusetts
      • Boston, Massachusetts, 미국, 02215
        • Dana Farber Cancer Institute
    • New York
      • New York, New York, 미국, 10032
        • Columbia University Medical Center New York Presbyterian
  • 이탈리아
    • GE
      • Genova, GE, 이탈리아, 16147
        • Novartis Investigative Site
    • RM
      • Roma, RM, 이탈리아, 00165
        • Novartis Investigative Site
  • 일본
      • Osaka, 일본, 5340021
        • Novartis Investigative Site
    • Kanagawa
      • Yokohama, Kanagawa, 일본, 2328555
        • Novartis Investigative Site
    • Tokyo
      • Shinjuku-ku, Tokyo, 일본, 1608582
        • Novartis Investigative Site
  • 중국
      • Beijing, 중국, 100044
        • Novartis Investigative Site
  • 태국
      • Chiang Mai, 태국, 50200
        • Novartis Investigative Site
    • THA
      • Khon Kaen, THA, 태국, 40002
        • Novartis Investigative Site
  • 터키 (Türkiye)
    • Fatih
      • Istanbul, Fatih, 터키 (Türkiye), 34093
        • Novartis Investigative Site
    • Nilufer
      • Bursa, Nilufer, 터키 (Türkiye), 16059
        • Novartis Investigative Site
  • 폴란드
      • Wroclaw, 폴란드, 50-367
        • Novartis Investigative Site
  • 프랑스
      • Lille, 프랑스, 59000
        • Novartis Investigative Site
      • Paris, 프랑스, 75019
        • Novartis Investigative Site

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

1년 (어린이)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

Inclusion Criteria:

  • Male or female participants:

    • Pediatric formulation group: ≥ 1 and less than 18 years of age at study entry.
    • Adult formulation group: ≥ 14 and less than 18 years of age and body weight of ≥ 40 kg at study entry.

  • Participants with Ph+ CML-CP must meet all of the following laboratory values at the screening visit. In the case where bone marrow blast and promyelocyte counts are available, these will be accepted if done within 56 days prior to the screening visit, to avoid unnecessary repetition of this test.

    1. < 15% blasts in peripheral blood and bone marrow
    2. < 30% combined blasts plus promyelocytes in peripheral blood and bone marrow
    3. < 20% basophils in the peripheral blood
    4. Neutrophils ≥ 1.5 x 10^9/L (or WBC ≥ 3 x 10^9/L if neutrophils are not available) and platelet count ≥ 100 x 10^9/L
    5. No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly

  • Prior treatment with a minimum of one TKI

  • Failure (adapted from the 2020 European Leukemia Net (ELN) Guidelines Hochhaus et al 2020 and 2013 ELN Guidelines Baccarani et al 2013) or intolerance to the most recent TKI therapy at the time of screening.

  • Performance status: Karnofsky ≥ 50% for patients ≥ 16 years of age, and Lansky ≥ 50 for patients < 16 years of age at the time of screening

  • Participants must have adequate renal, hepatic, pancreatic and cardiac function

  • Participants must have electrolyte values within normal limits or corrected to be within normal limits with supplements prior to first dose of study medication:

  • Evidence of typical BCR::ABL1 transcript [e14a2 and/or e13a2] at the time of screening which are amenable to standardized RQ-PCR quantification.

Exclusion Criteria:

  • Known presence of the T315I mutation prior to study entry or a BCR::ABL mutation with known resistance to study treatment any time prior to study entry.
  • Known second chronic phase of CML after previous progression to AP/BC.
  • Previous treatment with a hematopoietic stem-cell transplantation.
  • Patient planning to undergo allogeneic hematopoietic stem cell transplantation.
  • Cardiac or cardiac repolarization abnormality
  • Severe and/or uncontrolled concurrent medical disease that in the opinion of the Investigator could cause unacceptable safety risks or compromise compliance with the protocol
  • History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis.
  • History of acute or chronic liver disease.
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug
  • Pregnant or nursing (lactating) females.

Other protocol-defined inclusion/exclusion may apply.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 해당 없음
  • 중재 모델: 순차적 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: Asciminib

This arm consists of 2 groups:

  • The pediatric formulation group where the dose is based on body weight (1.3mg/kg BID or 2.6 mg/kg QD)
  • The adult formulation group where participants will receive a flat dose of 40mg BID
의약품: Asciminib Pediatric formulation group

Asciminib Pediatric formulation group: 1 mg film-coated granules in a size 0 capsule will be supplied, taken orally (capsules are a container for the granules and are not ingested):

10 mg (10x 1 mg film-coated granules in capsule) 15 mg (15x 1 mg film-coated granules in capsule) 30 mg (30x 1 mg film-coated granules in capsule)

다른 이름들:
  • ABL001
의약품: Asciminib Adult formulation group

Asciminib Adult formulation group:

40 mg tablets BID, taken orally. 20 mg tablets BID, taken orally.

다른 이름들:
  • ABL001

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Primary Pharmacokinetic (PK) parameter: AUClast
기간: 52 weeks

Goal: identifying the pediatric formulation dose (fed) leading to asciminib exposure comparable to 40 mg BID in adult patients (fasted).
52 weeks
Primary PK parameter: AUCtau
기간: 52 weeks

Goal: identifying the pediatric formulation dose (fed) leading to asciminib exposure comparable to 40 mg BID in adult patients (fasted).
52 weeks
Secondary PK parameter: Cmax
기간: 52 weeks

Goal: identifying the pediatric formulation dose (fed) leading to asciminib exposure comparable to 40 mg BID in adult patients (fasted).
52 weeks
Secondary PK parameter: Tmax
기간: 52 weeks

Goal: identifying the pediatric formulation dose (fed) leading to asciminib exposure comparable to 40 mg BID in adult patients (fasted).
52 weeks
Secondary PK parameter: Ctrough
기간: 52 weeks

Goal: identifying the pediatric formulation dose (fed) leading to asciminib exposure comparable to 40 mg BID in adult patients (fasted).
52 weeks

2차 결과 측정

결과 측정
측정값 설명
기간
Hematologic responses
기간: 52 weeks

Complete hematological response will be defined as all of the following present for ≥ 4 weeks:

  • WBC count < 10 x 10^9/L
  • Platelet count < 450 x 10^9/L
  • Basophils < 5%
  • No blasts and promyelocytes in peripheral blood
  • Myelocytes + metamyelocytes < 5% in peripheral blood
  • No evidence of extramedullary disease, including spleen and liver
52 weeks
Molecular responses
기간: 52 weeks

To assess pharmacodynamic markers of asciminib's anti-leukemic activity. Molecular response will be assessed by Breakpoint Cluster Region gene-Abelson proto-oncogene (BCR-ABL) 1 level.
52 weeks
Questionnaire on acceptability and palatability after first dose, 4 and 52 weeks
기간: after first dose at Week 1 Day 1, 4 weeks, 52 weeks

To assess acceptability and palatability of the pediatric formulation
after first dose at Week 1 Day 1, 4 weeks, 52 weeks

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Novartis Pharmaceuticals

수사관

  • 연구 책임자: Novartis Pharmaceuticals, Novartis Pharmaceuticals

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2021년 12월 27일

기본 완료 (추정된)

2027년 9월 3일

연구 완료 (추정된)

2031년 10월 2일

연구 등록 날짜

최초 제출

2021년 5월 18일

QC 기준을 충족하는 최초 제출

2021년 6월 7일

처음 게시됨 (실제)

2021년 6월 14일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 11월 9일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 11월 6일

마지막으로 확인됨

2026년 11월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • CABL001I12201
  • 2023- 508129-28 (기타 식별자: EU CTIS)
  • 2023 (미국 NIH 보조금/계약)

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

예

IPD 계획 설명

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

예

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

구독하다