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)
Blinatumomab: Dosing based on bone marrow disease burden and weight. Continuous IV infusion; Cycles 2, 3
Methotrexate (intrathecal): Intrathecal
Cytarabine (intrathecal): Intrathecal
Hydrocortisone (intrathecal): Intrathecal
Prednisolone (intrathecal): Intrathecal
Study summary
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
Sex
ALL
Min age
1 Year
Max age
30 Years
Healthy volunteers
No
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.
Primary outcome measure(s)
Part 1 Dose Escalation: Incidence of Dose Limiting Toxicities (DLTs) occurring during cycle 1 (debulking induction) — 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.
Part 1 Dose Escalation: Incidence and severity of adverse events (AEs) during cycle 1 (debulking induction) — 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.
Part 2 Dose Expansion: Percentage of complete response/remission (CR) evaluable participants who achieve CR treated at recommended phase 2 dose (RP2D) (debulking induction) — 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.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time.