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)

Novartis

Status and phase: Begins enrollment in 1 month; Phase 2; Phase 1

Conditions: Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia; Acute Lymphoblastic Leukemia; Leukemia, Lymphoblastic, Acute, Philadelphia-Positive

Treatments: Drug: Methotrexate (intrathecal); Drug: Asciminib Pediatric formulation; Drug: Hydrocortisone (intrathecal); Drug: Blinatumomab; Drug: Prednisolone (intrathecal); Drug: Asciminib Adult formulation; Drug: Cytarabine (intrathecal); Drug: Vincristine; Drug: Dexamethasone

Study type: Interventional

Funder types: Industry

Identifiers

NCT07387926

CABL001L12101

2025-522019-40 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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).

A separate cohort on this study will enroll participants with r/r ABL-class Ph-like 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:

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

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).

Enrollment: 50 estimated patients

Sex: All

Ages: 1 to 30 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

• 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

Single Arm

Experimental group

Description:

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.

Treatment:

Drug: Dexamethasone

Drug: Vincristine

Drug: Cytarabine (intrathecal)

Drug: Asciminib Adult formulation

Drug: Prednisolone (intrathecal)

Drug: Blinatumomab

Drug: Hydrocortisone (intrathecal)

Drug: Methotrexate (intrathecal)

Drug: Asciminib Pediatric formulation