AZD0486 as Monotherapy in B-cell Acute Lymphoblastic Leukaemia

Phase 2RecruitingNCT06137118

AstraZeneca163 enrolled

Overview

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)

This dose escalation and optimization study is evaluating the safety, tolerability, PK, PD and clinical activity of AZD0486 monotherapy in r/r B-ALL.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

163

Conditions

B-cell Acute Lymphoblastic Leukemia (B-ALL)

Interventions

AZD0486DRUG

Investigational Product administered via intravenous infusion.

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age: 12 years and above (Parts A, B and C). * Participants with B-cell Acute Lymphoblastic Leukemia with CD19 expression by local lab with: 1. Bone marrow infiltration with \>/= 5% blasts 2. Either relapsed or refractory after a minimum of 2 prior therapies or after 1 prior line of therapy if no SOC available option. 3. Philadelphia positive participants are allowed in all parts of the study, if intolerant or refractory to TKIs. * For participants older than 16 years, Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2. For Participants 16 years or younger, Lansky score more or equal to 50%. The above is a summary, other inclusion criteria details may apply. Exclusion Criteria: * 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. * History of other malignancy (with certain exceptions). * Unresolved AEs \>/= Grade 2, from prior therapies * Prior therapy with TCEs within 4 weeks, CAR T-cell therapy or autologous HSCT within 8 weeks or prior alloSCT within 12 weeks of start of therapy. * GVHD requiring immunosuppressive therapy within 3 weeks prior to AZD0486 treatment. The above is a summary, other exclusion criteria details may apply.

Locations (79)

Outcomes

Primary Outcomes

Part A: Frequency of DLTs

DLTs are dose-limiting toxicities as defined in the study protocol

Time frame: Up to 28 days

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 months

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 each

Secondary Outcomes

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 each

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 each

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 months

Parts A, B, C: Duration of CR, CR/CRh and CR/CRh/CRi

Central Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479 information.center@astrazeneca.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Research Site

Birmingham, Alabama, United States

WITHDRAWN

Research Site

Duarte, California, United States

RECRUITING

Research Site

Los Angeles, California, United States

RECRUITING

Research Site

Palo Alto, California, United States

RECRUITING

Research Site

Tampa, Florida, United States

RECRUITING

Research Site

Atlanta, Georgia, United States

RECRUITING

Research Site

Chicago, Illinois, United States

RECRUITING

Research Site

New York, New York, United States

RECRUITING

Research Site

Houston, Texas, United States

RECRUITING

Research Site

Richmond, Virginia, United States

RECRUITING

...and 69 more locations

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 months

Parts A, B, C: Event-free survival (EFS)

Event-free survival is defined as the time from the date of the first dose until the date of a relapse after achieving a CR/CRh/CRi, or death due to any cause, whichever occurs first.

Time frame: From First dose to last progression or data cutoff, whichever comes first, assessed up to 42 months

Parts A, B, C: Overall Survival (OS)

The OS is defined as the time from date of first dose until death due to any cause regardless of whether the participant withdraws from treatment or receives a TTNT.

Time frame: From First dose to data cutoff, up to 42 months

Parts B &C: Subsequent alloSCT or donor lymphocyte infusion if used as an alloSCT substitute

Percentage of participants who received a subsequent alloSCT, or DLI if used as an alloSCT substitute, post AZD0486 treatment

Time frame: From first dose to EOT, up to 42 Months

Part A, B, C:MRD-negative rate of CR

To evaluate the impact of AZD0486 on MRD-negative rate of CR, CR/CRh and CR/CRi

Time frame: From First dose to data cutoff, up to 42 months

Parts A, B, & C: PK characterization of AZD0486

Derived PK parameter: AUC