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.
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).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
oral, administered daily; Cycles 1, 2, 3
oral, administered daily; Cycles 1, 2, 3
Fixed doses, oral (preferred) or intravenous (IV) twice daily; Cycle 1, Days 1 - 14; (Cycle 1 = 28 days)
Fixed doses, IV, weekly; Cycle 1
Dosing based on bone marrow disease burden and weight. Continuous IV infusion; Cycles 2, 3
Intrathecal
Intrathecal
Intrathecal
Intrathecal
Part 1 Dose Escalation: To determine the Recommended Phase II Dose (RP2D) of asciminib when administered with low intensity chemotherapy
An integrated assessment of tolerability, safety profiles, dose-limiting toxicities (DLTs), treatment responses, and available pharmacokinetic (PK) data.
Time frame: During Cycle 1 (Cycle 1 = 28 days)
Part 2 Dose Expansion: Assess the rate of complete remission (CR) at RP2D
Percentage of participants achieving complete remission (CR)
Time frame: End of Cycle 1 (Cycle 1 = 28 days)
Complete remission (CR) rate
Percentage of participants achieving CR
Time frame: End of Cycle 2 and Cycle 3 (Cycle 2 & 3 = 42 days)
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)
Next generation sequencing (NGS) minimal residual disease (MRD) negative rate
Percentage of participants achieving NGS MRD negative CR/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)
Multiparametric flow cytometry (MFC) MRD negative CR/CRi rate
Percentage of participants achieving MRD negative CR/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)
Disease Free Survival (DFS)
The period from when a participant is in remission until they have relapse or death due to any reason.
Time frame: 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)
The duration of time from treatment initiation until the participant's death due to any reason.
Time frame: 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
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
Time frame: Cycle 1, Day 8 (Cycle 1 = 28 days)
PK parameter of asciminib at steady state: Cmax
Maximum concentration-the peak (highest) plasma drug concentration observed after administration
Time frame: Cycle 1, Day 8 (Cycle 1 = 28 days)
PK parameter of asciminib at steady state: Tmax
The time it takes to reach the Cmax after drug administration
Time frame: Cycle 1, Day 8 (Cycle 1 = 28 days)
PK parameter of asciminib at steady state: Ctrough
Trough concentration- lowest drug concentration observed, typically right before the next dose is administered (steady-state condition)
Time frame: Cycle 1, Day 8 (Cycle 1 = 28 days); Cycle 2, Day 22 (Cycle 2 = 42 days); Cycle 3, Day 22 (Cycle 3 = 42 days)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.