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Bezpečnost a účinnost přípravku Asciminib u dětí a mladých dospělých s relabující/refrakterní (r/r) Philadelphia pozitivní (Ph+) nebo ABL třídy Ph-like akutní lymfoblastickou leukémií (ALL)

10. listopadu 2026 aktualizováno: Novartis Pharmaceuticals

Otevřená, fáze I/II studie k vyhodnocení bezpečnosti a účinnosti asciminibu s chemoterapií následované asciminibem plus blinatumomabem u dětí, dospívajících a mladých dospělých s relabovanou nebo refrakterní BCR::ABL1-pozitivní (Philadelphia pozitivní, Ph+) nebo BCR::ABL1-podobnou (Ph-podobnou) ALL

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.

Přehled studie

Postavení

Nábor

Podmínky

Intervence / Léčba

Detailní popis

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).

Typ studie

Intervenční

Zápis (Odhadovaný)

50

Fáze

  • Fáze 2
  • Fáze 1

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní kontakt

Studijní záloha kontaktů

  • Jméno: Novartis Pharmaceuticals
  • Telefonní číslo: +41613241111

Studijní místa

  • Austrálie
    • New South Wales
      • Sydney, New South Wales, Austrálie, 2031
        • Nábor
        • Novartis Investigative Site
    • Queensland
      • Brisbane, Queensland, Austrálie, 4101
        • Nábor
        • Novartis Investigative Site
    • Victoria
      • Melbourne, Victoria, Austrálie, 3004
        • Nábor
        • Novartis Investigative Site
  • Francie
      • Marseille, Francie, 13885
        • Nábor
        • Novartis Investigative Site
  • Holandsko
      • Utrecht, Holandsko, 3584 CS
        • Nábor
        • Novartis Investigative Site
  • Izrael
      • Ramat Gan, Izrael, 5265601
        • Nábor
        • Novartis Investigative Site
  • Jižní Korea
      • Seoul, Jižní Korea, 03080
        • Nábor
        • Novartis Investigative Site
      • Seoul, Jižní Korea, 06591
        • Nábor
        • Novartis Investigative Site
  • Tchaj-wan
      • Taipei, Tchaj-wan, 10002
        • Nábor
        • Novartis Investigative Site

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

1 rok až 30 let (Dítě, Dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

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.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: N/A
  • Intervenční model: Přiřazení jedné skupiny
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: 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.
Lék: Asciminib Adult formulation

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

Ostatní jména:
  • ABL001
Lék: Asciminib Pediatric formulation

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

Ostatní jména:
  • ABL001
Lék: Dexamethasone

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

Lék: Vincristine

Fixed doses, IV, weekly; Cycle 1

Lék: Blinatumomab

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

Lék: Methotrexate (intrathecal)

Intrathecal

Lék: Cytarabine (intrathecal)

Intrathecal

Lék: Hydrocortisone (intrathecal)

Intrathecal

Lék: Prednisolone (intrathecal)

Intrathecal

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Part 1 Dose Escalation: Incidence of Dose Limiting Toxicities (DLTs) occurring during cycle 1 (debulking induction)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Complete remission (CR) rate
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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)
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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)

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Novartis Pharmaceuticals

Vyšetřovatelé

  • Ředitel studie: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Aktuální)

5. července 2026

Primární dokončení (Odhadovaný)

19. září 2033

Dokončení studie (Odhadovaný)

30. května 2036

Termíny zápisu do studia

První předloženo

13. ledna 2026

První předloženo, které splnilo kritéria kontroly kvality

27. ledna 2026

První zveřejněno (Aktuální)

4. února 2026

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

12. listopadu 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

10. listopadu 2026

Naposledy ověřeno

1. listopadu 2026

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • CABL001L12101
  • 2025-522019-40 (Číslo EudraCT)
  • 2025 (Grant/smlouva NIH USA)

Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

ANO

Popis plánu 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.

Typ podpůrných informací pro sdílení IPD

  • PROTOKOL STUDY

Informace o lécích a zařízeních, studijní dokumenty

Studuje lékový produkt regulovaný americkým FDA

Ano

Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

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