Study of AZD9829 in CD123+ Hematological Malignancies

Phase 2Active Not RecruitingNCT06179511

AstraZeneca56 enrolled

Overview

This is a modular, multicentre, open-label, Phase I/II, dose-setting study. AZD9829 will be administered intravenously as monotherapy or in combination in participants with CD123 positive hematological malignancies.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hematological Malignancies

Interventions

AZD9829DRUG

AZD9829 will be administered by IV infusion

AZD9829DRUG

AZD9829 will be administered by IV infusion

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * ≥18 years of age; * CD123+ hematologic malignancy based on flow cytometry or immunohistochemistry by local laboratory; * R/R AML (except APL); * R/R HR-MDS with ≥5% bone marrow blast at time of inclusion; * Had at least 1 prior line of therapy at currents histology, and have no available treatment options; * ECOG performance status of ≤ 2. The above is a summary, other inclusion criteria details may apply. Exclusion Criteria: * Active CNS leukemia; * Previous treatment with any CD123 targeting therapy; * Prior allogeneic HSCT, within 90 or cell therapy within 60 of start of therapy; * Active GVHD that requires immunosuppressive treatment within 4 weeks prior to start of AZD9829; * History of other malignancy(with certain exceptions); * Active and uncontrolled infections; * Unresolved AEs ≥2 Grade, from prior therapies. The above is a summary, other exclusion criteria details may apply .

Locations (22)

Research Site

Duarte, California, United States

Research Site

St Louis, Missouri, United States

Outcomes

Primary Outcomes

Frequency of dose limiting toxicities (DLTs).

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

Time frame: Module 1 - 28 days.

Safety evaluation of AZD9829: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Frequency, severity and relationship to study drug of AEs and SAEs

Time frame: Module 1 - From informed consent until 60 days after last dose of AZD9829.

Identify RP2D in R/R AML patients.

Incidence of AEs/SAEs and PK data

Time frame: Moldule 1 -From informed consent until 60 days after last dose of AZD9829.

Secondary Outcomes

Pharmacokinetics of AZD9829: Plasma Concentration of total antibody

Measurement of plasma concentration of conjugated and unconjugated antibody

Time frame: Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.

Pharmacokinetics of AZD9829: Plasma Concentration of total unconjugated warhead

Measurement of plasma concentration of total unconjugated warhead

Time frame: Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.

Pharmacokinetics of AZD9829: Area under the concentration time curve (AUC).

Area under the plasma concentration-time curve.

Time frame: Module 1 - From date of first dose of AZD9829up until 30 days post last dose.

Pharmacokinetics of AZD9829: Maximum plasma concentration of the study drug (Cmax).

Maximum observed plasma concentration of AZD9829.

Data from ClinicalTrials.gov

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Research Site

New York, New York, United States

Research Site

Chapel Hill, North Carolina, United States

Research Site

Columbus, Ohio, United States

Research Site

Houston, Texas, United States

Research Site

Milwaukee, Wisconsin, United States

Research Site

Heidelberg, Australia

Research Site

Melbourne, Australia

Research Site

Tianjin, China

...and 12 more locations

Time frame: Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.

Pharmacokinetics of AZD9829: Time to maximum concentration (tmax)

Time to maximum observed plasma concentration of the study drug.

Time frame: Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.

Pharmacokinetics of AZD9829: Clearance

The volume of plasma from which the study drug is completely removed per unit time.

Time frame: Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.

Pharmacokinetics of AZD9829: Half-life (t 1/2)

Terminal elimination half-life.

Time frame: Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.

Pharmacokinetics of AZD9829: Anti-Drug Antibodies (ADA)

Evaluating the number of patients who develop anti-drug antibodies (ADA) during treatment.

Time frame: Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.

Pharmacokinetics of AZD9829: Anti-Drug Antibodies (ADA)

Evaluating the percentage of patients who develop anti-drug antibodies (ADA) during treatment.

Time frame: Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.

To determine the immunogenicity of AZD9829.

The number of participants who develop ADA (Anti Drug Antibodies).

Time frame: Module 1 - From first dose to the 30-Day SFU visit

To determine the immunogenicity of AZD9829.

The percentage of participants who develop ADA (Anti Drug Antibodies).

Time frame: Module 1 - From first dose to the 30-Day SFU visit

Overall Response Rate (ORR)

Overall response rate disease assessments in accordance with ELN2022 recommendations for AML and IWG 2006/2018 for MDS.

Time frame: Module 1 - From first dose of AZD9829 until disease progression or end of the study (upto approximately 1 year)

Composite Complete Response Rate (CCRR)

Composite CR rate disease assessment in accordance with ELN2022 for AML and IWG 2006/2018 for MDS.

Time frame: Module 1 - From first dose of AZD9829 up to approximately 1 year.

Complete remission with incomplete hematologic recovery (CRi)

The endpoint of complete remission with CRi as defined by ELN2022 criteria.

Time frame: Module 1 - From first dose of AZD9829 up to approximately 1 year.

Complete Response (CR)

Complete response (CR) according to ELN2022 for AML and IWG 2006/2018 for MDS.

Time frame: Module 1 - From first dose of AZD9829 up to approximately 1 year.

Duration of Response (DoR)

Time from first documented response until the date of relapse or death.

Time frame: Module 1 -Time from first documented response until disease progression or death (approximately 1 year).

Time to Response (TTR)

Time from first dose to the achievement of first overall response. Disease assessments will follow ELN2022 for AML and IWG 2006/2018 for MDS.

Time frame: Module 1 - From first dose of AZD9829 until complete remission, disease progression or death (approximately 1 year).

Time to Next Treatment (TTNT)

The time from the start of treatment date until the date of subsequent antileukemia therapy.

Time frame: Module 1 - From first dose of AZD9829 until the date of subsequent anti-leukemia-therapy or death (approximately 1 year).

Progression-free Survival (PFS)

The time from the start of treatment date until the date of disease progression or death.

Time frame: Module 1 - From first dose of AZD9829 until disease progression or death (approximately 1 year).

Overall Survival (OS)

The time from the start of treatment date until death.

Time frame: Module 1 - From first dose of AZD9829 until death (approximately 1 year).

Event-free Survival (EFS)

The time from the start of treatment date to disease progression, death, or initiation of a new anti-leukemic therapy.

Time frame: Module 1 - From first dose of AZD9829 until disease progression, death, or initiation of a new anti-leukemic therapy (approximately 1 year).