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Sicherheit und Wirksamkeit von Asciminib bei pädiatrischen Patienten und jungen Erwachsenen mit rezidivierter/refraktärer (r/r) Philadelphia-positiver (Ph+) oder ABL-Klasse Ph-ähnlicher akuter lymphatischer Leukämie (ALL)

10. November 2026 aktualisiert von: Novartis Pharmaceuticals

Open-label-Studie der Phase I/II zur Bewertung der Sicherheit und Wirksamkeit von Asciminib in Kombination mit Chemotherapie, gefolgt von Asciminib plus Blinatumomab bei Kindern, Jugendlichen und jungen Erwachsenen mit rezidivierter oder refraktärer BCR::ABL1-positiver (Philadelphia-positiver, Ph+) oder BCR::ABL1-ähnlicher (Ph-ähnlicher) 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.

Studienübersicht

Status

Rekrutierung

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

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).

Studientyp

Interventionell

Einschreibung (Geschätzt)

50

Phase

  • Phase 2
  • Phase 1

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienkontakt

Studieren Sie die Kontaktsicherung

  • Name: Novartis Pharmaceuticals
  • Telefonnummer: +41613241111

Studienorte

  • Australien
    • New South Wales
      • Sydney, New South Wales, Australien, 2031
        • Rekrutierung
        • Novartis Investigative Site
    • Queensland
      • Brisbane, Queensland, Australien, 4101
        • Rekrutierung
        • Novartis Investigative Site
    • Victoria
      • Melbourne, Victoria, Australien, 3004
        • Rekrutierung
        • Novartis Investigative Site
  • Frankreich
      • Marseille, Frankreich, 13885
        • Rekrutierung
        • Novartis Investigative Site
  • Israel
      • Ramat Gan, Israel, 5265601
        • Rekrutierung
        • Novartis Investigative Site
  • Niederlande
      • Utrecht, Niederlande, 3584 CS
        • Rekrutierung
        • Novartis Investigative Site
  • Südkorea
      • Seoul, Südkorea, 03080
        • Rekrutierung
        • Novartis Investigative Site
      • Seoul, Südkorea, 06591
        • Rekrutierung
        • Novartis Investigative Site
  • Taiwan
      • Taipei, Taiwan, 10002
        • Rekrutierung
        • Novartis Investigative Site

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

1 Jahr bis 30 Jahre (Kind, Erwachsene)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

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.

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: N / A
  • Interventionsmodell: Einzelgruppenzuweisung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
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.
Arzneimittel: Asciminib Adult formulation

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

Andere Namen:
  • ABL001
Arzneimittel: Asciminib Pediatric formulation

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

Andere Namen:
  • ABL001
Arzneimittel: Dexamethasone

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

Arzneimittel: Vincristine

Fixed doses, IV, weekly; Cycle 1

Arzneimittel: Blinatumomab

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

Arzneimittel: Methotrexate (intrathecal)

Intrathecal

Arzneimittel: Cytarabine (intrathecal)

Intrathecal

Arzneimittel: Hydrocortisone (intrathecal)

Intrathecal

Arzneimittel: Prednisolone (intrathecal)

Intrathecal

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Part 1 Dose Escalation: Incidence of Dose Limiting Toxicities (DLTs) occurring during cycle 1 (debulking induction)
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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)

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Complete remission (CR) rate
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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)

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Novartis Pharmaceuticals

Ermittler

  • Studienleiter: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

5. Juli 2026

Primärer Abschluss (Geschätzt)

19. September 2033

Studienabschluss (Geschätzt)

30. Mai 2036

Studienanmeldedaten

Zuerst eingereicht

13. Januar 2026

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

27. Januar 2026

Zuerst gepostet (Tatsächlich)

4. Februar 2026

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

12. November 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

10. November 2026

Zuletzt verifiziert

1. November 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • CABL001L12101
  • 2025-522019-40 (EudraCT-Nummer)
  • 2025 (US NIH Stipendium/Vertrag)

Plan für individuelle Teilnehmerdaten (IPD)

Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?

JA

Beschreibung des IPD-Plans

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.

Art der unterstützenden IPD-Freigabeinformationen

  • STUDIENPROTOKOLL

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Ja

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

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