AZD0486 as Monotherapy in B-cell Acute Lymphoblastic Leukaemia
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age12+
SponsorAstraZeneca
About this trial
This is a Phase 1/2, global multicentre, open-label, single-arm, dose escalation and dose optimisation study of AZD0486 to evaluate the safety, tolerability, and efficacy of AZD0486 monotherapy in participants with R/R B ALL who have received ≥ 2 prior lines of therapies. The study will consist of 3 parts. Part A monotherapy dose escalation. Part B dose optimisation. Part C Dose expansion at the recommended phase 2 dose (RP2D)
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age: 12 years and above (Parts A, B and C).
Bone marrow infiltration with >/= 5% blasts
Either relapsed or refractory after a minimum of 2 prior therapies or after 1 prior line of therapy if no SOC available option.
Philadelphia positive participants are allowed in all parts of the study, if intolerant or refractory to TKIs.
Disqualifiers
Active CNS involvement by B-ALL, defined by presence of ALL blasts in CSF (CNS2 and CNS3 criteria).
Isolated extramedullary disease relapse.
Testicular leukemia
History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis; or prior Grade 4 neurotoxicity with CAR-T or TCE therapy.
Trial design
Design model
Sequential
Treatments tested in this trial
AZD0486
DrugInvestigational Product administered via intravenous infusion.
Treatment groups
236 Participants
are divided into 3 treatment groupsGroup A: Part A: AZD0486 Dose EscalationExperimental treatment 1 intervention
Group B: Part B: Dose OptimizationExperimental treatment 1 intervention
Group C: Part C: Dose ExpansionExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Part A: Frequency of DLTs
DLTs are dose-limiting toxicities as defined in the study protocol
Time frame
Up to 28 days2
Parts A & B: Safety Evaluation of AZD0486
Frequency, severity, and relationship to study drug of AEs and SAEs; dose modifications; changes in laboratory evaluations; QTc, and vital signs changes.
Time frame
From signing of informed consent through data cutoff, up to 42 months3
Parts B & C: Rate of CR within 3 cycles
To evaluate the efficacy of AZD0486 based on NCCN response criteria (in Part B and C).
Time frame
Up to three cycles of 28 days eachSecondary outcomes
1
Part A: Rate of CR within 3 cycles
the percentage of participants with a best response of CR within 3 cycles based on NCCN response criteria by investigators
Time frame
Up to 3 cycles of 28 days each2
Part A,B,C: Rate of CR/CRh and CR/CRh/CRi within 3 cycles
proportion of participants achieving CR/CRh/CRi within 3 cycles based on NCCN response criteria by investigators (Part A) based on the response evaluable population, and by central review confirmation (Parts B and C) based on the FAS.
Time frame
Up to 3 cycles of 28 days each3
Parts A, B, C: Rate of CR, CR/CRh and CR/CRh/CRi at any time during the study
Rate of CR, CR/CRh and CR/CRh/CRi at any time during study (Best CR, best CR/CRh and best CR/CRh/CRi)
Time frame
From first dose to end of treatment or data cutoff, whichever comes first, assessed up to 42 months4
Parts A, B, C: Duration of CR, CR/CRh and CR/CRh/CRi
the time from the date of first documented CR, CR/CRh, or CR/CRh/CRi response, respectively, until the date of documented relapse or death due to any cause in the absence of disease progression or relapse, whichever occurs earlier.
Time frame
From first dose to last progression or data cutoff, whichever comes first, assessed up to 42 monthsSponsors and contacts
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Source ClinicalTrials.gov