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Sicurezza ed Efficacia di Asciminib in Pazienti Pediatrici e Giovani Adulti con Leucemia Linfoblastica Acuta (LLA) Philadelphia Positiva (Ph+) o ABL-class Ph-like Refrattaria/Ricaduta (r/r)

10 novembre 2026 aggiornato da: Novartis Pharmaceuticals

Studio in aperto di Fase I/II per valutare la sicurezza e l'efficacia di Asciminib con chemioterapia seguito da Asciminib più Blinatumomab in pazienti pediatrici, adolescenti e giovani adulti con ALL BCR::ABL1-positiva (Philadelphia positiva, Ph+) o di tipo BCR::ABL1 (Ph-like) recidivata o refrattaria

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.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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 di studio

Interventistico

Iscrizione (Stimato)

50

Fase

  • Fase 2
  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

  • Nome: Novartis Pharmaceuticals
  • Numero di telefono: +41613241111

Luoghi di studio

  • Australia
    • New South Wales
      • Sydney, New South Wales, Australia, 2031
        • Reclutamento
        • Novartis Investigative Site
    • Queensland
      • Brisbane, Queensland, Australia, 4101
        • Reclutamento
        • Novartis Investigative Site
    • Victoria
      • Melbourne, Victoria, Australia, 3004
        • Reclutamento
        • Novartis Investigative Site
  • Corea del Sud
      • Seoul, Corea del Sud, 03080
        • Reclutamento
        • Novartis Investigative Site
      • Seoul, Corea del Sud, 06591
        • Reclutamento
        • Novartis Investigative Site
  • Francia
      • Marseille, Francia, 13885
        • Reclutamento
        • Novartis Investigative Site
  • Israele
      • Ramat Gan, Israele, 5265601
        • Reclutamento
        • Novartis Investigative Site
  • Olanda
      • Utrecht, Olanda, 3584 CS
        • Reclutamento
        • Novartis Investigative Site
  • Taiwan
      • Taipei, Taiwan, 10002
        • Reclutamento
        • Novartis Investigative Site

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 1 anno a 30 anni (Bambino, Adulto)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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.
Droga: Asciminib Adult formulation

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

Altri nomi:
  • ABL001
Droga: Asciminib Pediatric formulation

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

Altri nomi:
  • ABL001
Droga: Dexamethasone

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

Droga: Vincristine

Fixed doses, IV, weekly; Cycle 1

Droga: Blinatumomab

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

Droga: Methotrexate (intrathecal)

Intrathecal

Droga: Cytarabine (intrathecal)

Intrathecal

Droga: Hydrocortisone (intrathecal)

Intrathecal

Droga: Prednisolone (intrathecal)

Intrathecal

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Part 1 Dose Escalation: Incidence of Dose Limiting Toxicities (DLTs) occurring during cycle 1 (debulking induction)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Complete remission (CR) rate
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Novartis Pharmaceuticals

Investigatori

  • Direttore dello studio: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

5 luglio 2026

Completamento primario (Stimato)

19 settembre 2033

Completamento dello studio (Stimato)

30 maggio 2036

Date di iscrizione allo studio

Primo inviato

13 gennaio 2026

Primo inviato che soddisfa i criteri di controllo qualità

27 gennaio 2026

Primo Inserito (Effettivo)

4 febbraio 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

12 novembre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

10 novembre 2026

Ultimo verificato

1 novembre 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • CABL001L12101
  • 2025-522019-40 (Numero EudraCT)
  • 2025 (Sovvenzione/contratto NIH degli Stati Uniti)

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

SÌ

Descrizione del piano 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 di informazioni di supporto alla condivisione IPD

  • STUDIO_PROTOCOLLO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

Sì

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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