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Undersøgelse for at bestemme dosis og sikkerhed af asciminib hos pædiatriske patienter med kronisk myeloid leukæmi

23. september 2026 opdateret af: Novartis Pharmaceuticals

En multicenter, åben-label undersøgelse til bestemmelse af dosis og sikkerhed af oral asciminib hos pædiatriske patienter med Philadelphia-kromosompositiv kronisk myeloid leukæmi i kronisk fase (Ph+ CML-CP), tidligere behandlet med en eller flere tyrosinkinasehæmmere

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.

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

34

Fase

  • Fase 2
  • Fase 1

Udvidet adgang

Ledig uden for det kliniske forsøg. Se udvidet adgangsregistrering.

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Undersøgelse Kontakt Backup

  • Navn: Novartis Pharmaceuticals
  • Telefonnummer: +41613241111

Studiesteder

  • Forenede Stater
    • Indiana
      • Indianapolis, Indiana, Forenede Stater, 46202-5167
        • Aktiv, ikke rekrutterende
        • Indiana UH Riley H for CIU
    • Massachusetts
      • Boston, Massachusetts, Forenede Stater, 02215
        • Aktiv, ikke rekrutterende
        • Dana Farber Cancer Institute
    • Mississippi
      • Jackson, Mississippi, Forenede Stater, 39216-4505
        • Rekruttering
        • University of Mississippi Medical Center
        • Ledende efterforsker:
          • Dereck B Davis
        • Kontakt:
    • New York
      • New York, New York, Forenede Stater, 10032
        • Aktiv, ikke rekrutterende
        • Columbia University Medical Center New York Presbyterian
    • Ohio
      • Cincinnati, Ohio, Forenede Stater, 45229-3039
        • Trukket tilbage
        • Cinn Children Hosp Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forenede Stater, 19104-4399
        • Trukket tilbage
        • Childrens Hospital of Philadelphia
    • Texas
      • Houston, Texas, Forenede Stater, 77024
        • Trukket tilbage
        • Uni Of Texas MD Anderson Cancer Ctr
    • Utah
      • Salt Lake City, Utah, Forenede Stater, 84132
        • Trukket tilbage
        • University Of Utah
  • Frankrig
      • Bordeaux, Frankrig, 33076
        • Trukket tilbage
        • Novartis Investigative Site
      • Lille, Frankrig, 59000
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
      • Paris, Frankrig, 75019
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
      • Poitiers, Frankrig, 86021
        • Trukket tilbage
        • Novartis Investigative Site
  • Grækenland
      • Athens, Grækenland, 115 27
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
  • Holland
      • Utrecht, Holland, 3584 CS
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
  • Italien
    • GE
      • Genova, GE, Italien, 16147
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
    • MB
      • Monza, MB, Italien, 20900
        • Trukket tilbage
        • Novartis Investigative Site
    • RM
      • Roma, RM, Italien, 00165
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
    • TO
      • Torino, TO, Italien, 10126
        • Trukket tilbage
        • Novartis Investigative Site
  • Japan
      • Osaka, Japan, 5340021
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
    • Kanagawa
      • Yokohama, Kanagawa, Japan, 2328555
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
    • Tokyo
      • Shinjuku-ku, Tokyo, Japan, 1608582
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
  • Kina
      • Beijing, Kina, 100044
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
      • Shanghai, Kina, 200127
        • Trukket tilbage
        • Novartis Investigative Site
      • Tianjin, Kina, 300020
        • Trukket tilbage
        • Novartis Investigative Site
    • Zhejiang
      • Hangzhou, Zhejiang, Kina, 310052
        • Trukket tilbage
        • Novartis Investigative Site
  • Polen
      • Wroclaw, Polen, 50-367
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
  • Rusland
      • Moscow, Rusland, 117198
        • Trukket tilbage
        • Novartis Investigative Site
      • Saint Petersburg, Rusland, 197022
        • Trukket tilbage
        • Novartis Investigative Site
  • Sydkorea
      • Seoul, Sydkorea, 03080
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
      • Seoul, Sydkorea, 05505
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
  • Thailand
      • Bangkok, Thailand, 10400
        • Trukket tilbage
        • Novartis Investigative Site
      • Chiang Mai, Thailand, 50200
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
    • THA
      • Khon Kaen, THA, Thailand, 40002
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
  • Tyrkiet (Türkiye)
    • Fatih
      • Istanbul, Fatih, Tyrkiet (Türkiye), 34093
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
    • Nilufer
      • Bursa, Nilufer, Tyrkiet (Türkiye), 16059
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
  • Tyskland
      • Erlangen, Tyskland, 91054
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
      • Essen, Tyskland, 45147
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
      • Hamburg, Tyskland, 20246
        • Aktiv, ikke rekrutterende
        • Novartis Investigative Site
  • Ungarn
      • Budapest, Ungarn, 1083
        • Trukket tilbage
        • Novartis Investigative Site

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

1 år til 17 år (Barn)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Sekventiel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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
Medicin: 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)

Andre navne:
  • ABL001
Medicin: Asciminib Adult formulation group

Asciminib Adult formulation group:

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

Andre navne:
  • ABL001

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Primary Pharmacokinetic (PK) parameter: AUClast
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 52 weeks

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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Hematologic responses
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Novartis Pharmaceuticals

Efterforskere

  • Studieleder: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

27. december 2021

Primær færdiggørelse (Anslået)

2. september 2027

Studieafslutning (Anslået)

1. oktober 2031

Datoer for studieregistrering

Først indsendt

18. maj 2021

Først indsendt, der opfyldte QC-kriterier

7. juni 2021

Først opslået (Faktiske)

14. juni 2021

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

25. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

23. september 2026

Sidst verificeret

1. september 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • CABL001I12201
  • 2023- 508129-28 (Anden identifikator: EU CTIS)
  • 2023 (U.S. NIH-bevilling/kontrakt)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

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.

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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