Esta página foi traduzida automaticamente e a precisão da tradução não é garantida. Por favor, consulte o versão em inglês para um texto fonte.

Segurança e Eficácia do Asciminib em Pediatria e Jovens Adultos com Leucemia Linfoblástica Aguda (LLA) Filadélfia Positiva (Ph+) ou Semelhante a ABL-class Ph Recidivante/Refratária (r/r)

10 de novembro de 2026 atualizado por: Novartis Pharmaceuticals

Estudo Aberto, de Fase I/II para Avaliar a Segurança e Eficácia de Asciminib com Quimioterapia, seguido de Asciminib mais Blinatumomab em Crianças, Adolescentes e Jovens Adultos com LLA BCR::ABL1-positiva (Filadélfia Positiva, Ph+) ou BCR::ABL1-like (Ph-like) Recidivada ou Refratária

Multi-center, open-label, single arm study of asciminib in participants aged ≥1 year to ≤30 years old with r/r Ph+ or ABL-class Ph-like ALL. This study will have 2 parts: Part 1 dose escalation and Part 2 dose expansion. Part 1 dose escalation will enroll participants aged ≥1 year to ≤30 years to determine the recommended phase 2 dose (RP2D) of asciminib when administered with low intensity chemotherapy. Part 2 dose expansion will enroll participants aged ≥1 year to ≤30 years to evaluate safety, tolerability, and efficacy of asciminib at the RP2D with the treatment regimen.

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Descrição detalhada

This is a single arm phase I/II multicenter study to assess the safety and efficacy of asciminib at the RP2D in combination with low intensity chemotherapy (debulking induction) followed by asciminib plus blinatumomab (consolidation) in pediatric and young adult participants with r/r Ph+ ALL (inclusive of participants with T315I mutation).

The aim of the study design is to explore a novel treatment regimen which is expected to be more tolerable than the high intensity chemotherapy backbone-based regimens.

This study will consist of a 2-part design:

Part 1 dose escalation using a Bayesian Optimal Interval (BOIN) statistical design, and after determination of RP2D Part 2 dose expansion.

Participants will only enroll in either Part 1 or Part 2, and not both.

Both Part 1 and Part 2 (dose escalation and dose expansion) will have the following phases:

  • Core Study Treatment Phase
  • Survival Follow up Phase

Participants with known T315I mutation will not participate in Part 1 or Part 2. They will be part of a separate cohort.

The core study treatment phase will consist of 3 cycles of therapy: cycle 1 asciminib with low intensity chemotherapy (debulking induction), followed by cycle 2 (blinatumomab-block 1 with asciminib) and cycle 3 (blinatumomab-block 2 with asciminib).

Tipo de estudo

Intervencional

Inscrição (Estimado)

50

Estágio

  • Fase 2
  • Fase 1

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Estude backup de contato

  • Nome: Novartis Pharmaceuticals
  • Número de telefone: +41613241111

Locais de estudo

  • Austrália
    • New South Wales
      • Sydney, New South Wales, Austrália, 2031
        • Recrutamento
        • Novartis Investigative Site
    • Queensland
      • Brisbane, Queensland, Austrália, 4101
        • Recrutamento
        • Novartis Investigative Site
    • Victoria
      • Melbourne, Victoria, Austrália, 3004
        • Recrutamento
        • Novartis Investigative Site
  • Coréia do Sul
      • Seoul, Coréia do Sul, 03080
        • Recrutamento
        • Novartis Investigative Site
      • Seoul, Coréia do Sul, 06591
        • Recrutamento
        • Novartis Investigative Site
  • França
      • Marseille, França, 13885
        • Recrutamento
        • Novartis Investigative Site
  • Holanda
      • Utrecht, Holanda, 3584 CS
        • Recrutamento
        • Novartis Investigative Site
  • Israel
      • Ramat Gan, Israel, 5265601
        • Recrutamento
        • Novartis Investigative Site
  • Taiwan
      • Taipei, Taiwan, 10002
        • Recrutamento
        • Novartis Investigative Site

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

1 ano a 30 anos (Filho, Adulto)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria:

  • Evidence of Ph+ ALL or ABL1 or ABL2 fusion Ph-like ALL, inclusive of participants with ABL1 T315I mutation

  • Participants with CNS1, CNS2, CNS3a, or CNS3b at screening

  • Active B-Cell ALL at screening defined by MFC or IG/TCR PCR of ALL blasts >0.01% in participants with either:

    1. Primary refractory disease (>0.01% ALL blasts present at the end of consolidation) OR
    2. Relapsed ALL with evidence of involvement of BM with ALL (MFC or IG/TCR PCR >0.01%) after at least one line of therapy

  • Documented history of CD19 expressing B-cell ALL (in peripheral blood or bone marrow by flow cytometry).

    a) For participants who received anti-CD19 targeted therapy (e.g CD19 CAR T cells or blinatumomab), CD19 expressing B-cell ALL must be documented after anti-CD19 therapy completion prior to cycle 1 day 1

  • Adequate hepatic and renal function (local laboratory analysis) as defined:

    1. ALT ≤ 5x upper limit of normal (ULN) for age
    2. Total bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x ULN) for age, except for participants with Gilbert's syndrome who may only be included if total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN
    3. Estimated glomerular filtration rate (eGFR) using the Cockcroft-Gault formula in participants ≥ 18 years, OR radioisotope GFR ≥50 mL/min/1.73 m^2, OR creatinine based on age and sex for participants < 18 years old

  • Adequate cardiac function defined as shortening fraction ≥27% by echocardiogram (ECHO) OR left ventricular ejection fraction of ≥50% by ECHO

Exclusion Criteria:

  • Participants with >3 relapses of ALL
  • Extramedullary disease (non-CNS and/or isolated CNS disease)
  • Participants with CNS3c (Clinical signs of CNS leukemia (such as facial nerve palsy, brain/eye involvement or hypothalamic syndrome))
  • Cardiac or cardiac repolarization abnormality, including but not limited to clinically significant cardiac arrhythmias, long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome or other clinically significant heart disease (e.g., congestive heart failure, etc.)
  • 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.

Other protocol defined inclusion/exclusion criteria may apply.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: N / D
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: Single Arm

Asciminib Adult formulation group: escalating doses evaluated

Asciminib Pediatric formulation group: dose is based on body weight; dose level being evaluated will be converted into a mg/kg daily dose.

For known T315I mutation:

Fixed asciminib dose twice daily or the pediatric formulation dose equivalent twice daily.
Medicamento: Asciminib Adult formulation

oral, administered daily (twice daily for participants with known T315I mutation); Cycles 1, 2, 3

Outros nomes:
  • ABL001
Medicamento: Asciminib Pediatric formulation

oral, administered daily (twice daily for participants with known T315I mutation); Cycles 1, 2, 3

Outros nomes:
  • ABL001
Medicamento: Dexamethasone

Fixed doses, oral (preferred) or intravenous (IV) twice daily; Cycle 1, Days 1 - 14; (Cycle 1 = 28 days)

Medicamento: Vincristine

Fixed doses, IV, weekly; Cycle 1

Medicamento: Blinatumomab

Dosing based on bone marrow disease burden and weight. Continuous IV infusion; Cycles 2, 3

Medicamento: Methotrexate (intrathecal)

Intrathecal

Medicamento: Cytarabine (intrathecal)

Intrathecal

Medicamento: Hydrocortisone (intrathecal)

Intrathecal

Medicamento: Prednisolone (intrathecal)

Intrathecal

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Part 1 Dose Escalation: Incidence of Dose Limiting Toxicities (DLTs) occurring during cycle 1 (debulking induction)
Prazo: During Cycle 1 (Cycle 1 = 28 days)

A dose-limiting toxicity (DLT) is defined as an adverse event which starts between Day 1 and Day 28, is suspected by the investigator to be related to asciminib, and meets one of the several criteria.
During Cycle 1 (Cycle 1 = 28 days)
Part 1 Dose Escalation: Incidence and severity of adverse events (AEs) during cycle 1 (debulking induction)
Prazo: During Cycle 1 (Cycle = 28 days)

An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
During Cycle 1 (Cycle = 28 days)
Part 2 Dose Expansion: Percentage of complete response/remission (CR) evaluable participants who achieve CR treated at recommended phase 2 dose (RP2D) (debulking induction)
Prazo: End of Cycle 1 (Cycle 1 = 28 days)

Participants with Complete Response/Remission (CR) will achieve the following:

No circulating blasts or extramedullary disease; No lymphadenopathy, splenomegaly, skin/gum infiltration, testicular mass/CNS involvement; Marrow <5% blasts (M1) OR < 1% blasts by flow cytometry. If a discrepancy occurs between disease detection methods, the result of the flow cytometry assay will be used to determine CR status; Peripheral blood count recovery; ANC > 1000μL and platelets > 100,000μL.

CR evaluable: Participants will be considered CR evaluable for Part 2 if they have relapsed/refractory Ph+ ALL defined as either >1% bone marrow (BM) blasts by MFC or immunoglobulin/T-cell receptor (IG/TCR) PCR, OR > 5% BM blasts by morphologic evaluation at enrollment and are treated at RP2D.
End of Cycle 1 (Cycle 1 = 28 days)

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Complete remission (CR) rate
Prazo: End of Cycle 2 and Cycle 3 (Cycle 2 & 3 = 42 days)

Percentage of participants who had a CR
End of Cycle 2 and Cycle 3 (Cycle 2 & 3 = 42 days)
Overall response rate (ORR)
Prazo: At and by the end of Cycle 1 (Cycle 1 = 28 days), Cycle 2, and Cycle 3 (Cycle 2 & 3 = 42 days)

Percentage of participants who had CR and/or complete remission with incomplete blood count recovery (CRi)
At and by the end of Cycle 1 (Cycle 1 = 28 days), Cycle 2, and Cycle 3 (Cycle 2 & 3 = 42 days)
Next generation sequencing (NGS) minimal residual disease (MRD) negative rate
Prazo: At and by the end of Cycle 1 (Cycle 1 = 28 days), Cycle 2, and Cycle 3 (Cycle 2 & 3 = 42 days)

Percentage of participants who have NGS MRD negative CR at and by the end of cycle 1 (debulking induction), cycle 2 and cycle 3 (consolidation).
At and by the end of Cycle 1 (Cycle 1 = 28 days), Cycle 2, and Cycle 3 (Cycle 2 & 3 = 42 days)
Multiparametric flow cytometry (MFC) MRD negative CR rate
Prazo: At and by the end of Cycle 1 (Cycle 1 = 28 days), Cycle 2, and Cycle 3 (Cycle 2 & 3 = 42 days)

Percentage of participants who have MFC MRD negative CR at and by the end of cycle 1 (debulking induction), cycle 2 and cycle 3 (consolidation).
At and by the end of Cycle 1 (Cycle 1 = 28 days), Cycle 2, and Cycle 3 (Cycle 2 & 3 = 42 days)
Overall MRD negative response (MRD negative CR and/or CRi rate) by NGS
Prazo: at and by the end of cycle 1 (debulking induction) (Cycle 1 = 28 days), cycle 2, and cycle 3 (consolidation) (each cycle = 42 days)

Overall MRD negative response is the percentage of participants who have NGS MRD negative complete response (CR) and complete response incomplete blood count recovery (CRi).
at and by the end of cycle 1 (debulking induction) (Cycle 1 = 28 days), cycle 2, and cycle 3 (consolidation) (each cycle = 42 days)
Overall MRD negative response (MRD negative CR and/or CRi rate) by MFC
Prazo: at and by the end of cycle 1 (Cycle 1 = 28 days) (debulking induction), cycle 2, cycle 3 (consolidation) (each cycle = 42 days)

Overall MRD negative response is the percentage of participants who have MFC MRD negative complete response (CR) and complete response incomplete blood count recovery (CRi).
at and by the end of cycle 1 (Cycle 1 = 28 days) (debulking induction), cycle 2, cycle 3 (consolidation) (each cycle = 42 days)
Disease Free Survival (DFS)
Prazo: End of Cycle 3 (Cycle 3 = 42 days) in Part 2 of the study and at the end of study (EOS = approx. 3 years)

The period from when a participant is in remission until they have relapse or death due to any reason.
End of Cycle 3 (Cycle 3 = 42 days) in Part 2 of the study and at the end of study (EOS = approx. 3 years)
Overall survival (OS)
Prazo: End of Cycle 3 (Cycle 3 = 42 days) in Part 2 of the study and at the end of study (EOS = approx. 3 years)

The duration of time from treatment initiation until the participant's death due to any reason.
End of Cycle 3 (Cycle 3 = 42 days) in Part 2 of the study and at the end of study (EOS = approx. 3 years)
Pharmacokinetic (PK) parameter of asciminib at steady state: AUClast
Prazo: Cycle 1, Day 8 (Cycle 1 = 28 days)

Area Under the Curve to the Last Measurable Concentration-represents the total drug exposure (area under the plasma concentration-time curve) from the time of administration until the last measurable concentration
Cycle 1, Day 8 (Cycle 1 = 28 days)
PK parameter of asciminib at steady state: Cmax
Prazo: Cycle 1, Day 8 (Cycle 1 = 28 days)

Maximum concentration-the peak (highest) plasma drug concentration observed after administration
Cycle 1, Day 8 (Cycle 1 = 28 days)
PK parameter of asciminib at steady state: Tmax
Prazo: Cycle 1, Day 8 (Cycle 1 = 28 days)

The time it takes to reach the Cmax after drug administration
Cycle 1, Day 8 (Cycle 1 = 28 days)
PK parameter of asciminib at steady state: Ctrough
Prazo: Cycle 1, Day 8 (Cycle 1 = 28 days); Cycle 2, Day 22 (Cycle 2 = 42 days); Cycle 3, Day 22 (Cycle 3 = 42 days)

Trough concentration- lowest drug concentration observed, typically right before the next dose is administered (steady-state condition)
Cycle 1, Day 8 (Cycle 1 = 28 days); Cycle 2, Day 22 (Cycle 2 = 42 days); Cycle 3, Day 22 (Cycle 3 = 42 days)

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Novartis Pharmaceuticals

Investigadores

  • Diretor de estudo: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

5 de julho de 2026

Conclusão Primária (Estimado)

19 de setembro de 2033

Conclusão do estudo (Estimado)

30 de maio de 2036

Datas de inscrição no estudo

Enviado pela primeira vez

13 de janeiro de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

27 de janeiro de 2026

Primeira postagem (Real)

4 de fevereiro de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

12 de novembro de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

10 de novembro de 2026

Última verificação

1 de novembro de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • CABL001L12101
  • 2025-522019-40 (Número EudraCT)
  • 2025 (Concessão/Contrato do NIH dos EUA)

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

SIM

Descrição do plano IPD

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.

Tipo de informação de suporte de compartilhamento de IPD

  • PROTOCOLO DE ESTUDO

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Sim

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

Se inscrever