Health Trials

Safety and Efficacy of Asciminib in Pediatrics and Young Adults With Relapse/Refractory (r/r) Philadelphia Positive (Ph+) or ABL-class Ph-like Acute Lymphoblastic Leukemia (ALL)

ConditionsAcute Lymphoblastic LeukemiaLeukemia, Lymphoblastic, Acute, Philadelphia-PositivePhiladelphia Chromosome Positive Acute Lymphoblastic Leukemia
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age1-30
SponsorNovartis Pharmaceuticals

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Primary refractory disease (>0.01% ALL blasts present at the end of consolidation) OR

Relapsed ALL with evidence of involvement of BM with ALL (MFC or IG/TCR PCR >0.01%) after at least one line of therapy

Disqualifiers

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.)

Trial design

Design model

Single group

Treatments tested in this trial

  • Asciminib Adult formulation

    Drug

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

  • Asciminib Pediatric formulation

    Drug

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

  • Dexamethasone

    Drug

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

  • Vincristine

    Drug

    Fixed doses, IV, weekly; Cycle 1

  • Blinatumomab

    Drug

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

  • Methotrexate (intrathecal)

    Drug

    Intrathecal

  • Cytarabine (intrathecal)

    Drug

    Intrathecal

  • Hydrocortisone (intrathecal)

    Drug

    Intrathecal

  • Prednisolone (intrathecal)

    Drug

    Intrathecal

Treatment groups

50 Participants
are divided into 1 treatment group
Group A: Single ArmExperimental treatment 9 interventions

Trial outcomes

Primary outcomes

1

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

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.

Time frame
During Cycle 1 (Cycle 1 = 28 days)
2

Part 1 Dose Escalation: Incidence and severity of adverse events (AEs) during cycle 1 (debulking induction)

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.

Time frame
During Cycle 1 (Cycle = 28 days)
3

Part 2 Dose Expansion: Percentage of complete response/remission (CR) evaluable participants who achieve CR treated at recommended phase 2 dose (RP2D) (debulking induction)

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.

Time frame
End of Cycle 1 (Cycle 1 = 28 days)

Secondary outcomes

1

Complete remission (CR) rate

Percentage of participants who had a CR

Time frame
End of Cycle 2 and Cycle 3 (Cycle 2 & 3 = 42 days)
2

Overall response rate (ORR)

Percentage of participants who had CR and/or complete remission with incomplete blood count recovery (CRi)

Time frame
At and by the end of Cycle 1 (Cycle 1 = 28 days), Cycle 2, and Cycle 3 (Cycle 2 & 3 = 42 days)
3

Next generation sequencing (NGS) minimal residual disease (MRD) negative rate

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).

Time frame
At and by the end of Cycle 1 (Cycle 1 = 28 days), Cycle 2, and Cycle 3 (Cycle 2 & 3 = 42 days)
4

Multiparametric flow cytometry (MFC) MRD negative CR rate

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).

Time frame
At and by the end of Cycle 1 (Cycle 1 = 28 days), Cycle 2, and Cycle 3 (Cycle 2 & 3 = 42 days)

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Novartis Pharmaceuticals

Lead sponsor

Source ClinicalTrials.gov
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