Study of AZD9829 in CD123+ Hematological Malignancies

Hematological Malignancies Clinical Trial

Official title:

A Modular Phase I/II, Open-label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of AZD9829 as Monotherapy or in Combination in Patients With CD123-Positive Hematological Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06179511
• Other study ID #: D9470C00001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 31, 2024
• Est. completion date: August 4, 2026

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 65
• Est. completion date: August 4, 2026
• Est. primary completion date: August 4, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• =18 years of age;
• CD123+ hematologic malignancy based on flow cytometry or immunohistochemistry by local laboratory;
• R/R AML;
• 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.

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematological Malignancies
• Neoplasms

Intervention

Drug:
• AZD9829
AZD9829 will be administered by IV infusion

Locations

Country	Name	City	State
Australia	Research Site	Heidelberg
Australia	Research Site	Melbourne
China	Research Site	Tianjian
Germany	Research Site	Frankfurt
Italy	Research Site	Bologna
Japan	Research Site	Kashiwa
Japan	Research Site	Osaka-shi
Japan	Research Site	Yoshida-gun
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Spain	Research Site	Barcelona
Spain	Research Site	Salamanca
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
United States	Research Site	Chapel Hill	North Carolina
United States	Research Site	Columbus	Ohio
United States	Research Site	Duarte	California
United States	Research Site	Houston	Texas
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	New York	New York
United States	Research Site	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  China,  Germany,  Italy,  Japan,  Korea, Republic of,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of dose limiting toxicities (DLTs).	DLTs are dose-limiting toxicities as defined in the study protocol.	Module 1 - 28 days.
Primary	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	Module 1 - From informed consent until 30 days after last dose of AZD9829.
Secondary	Pharmacokinetics of AZD9829: Plasma Concentration of total antibody	Measurement of plasma concentration of conjugated and unconjugated antibody	Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.
Secondary	Pharmacokinetics of AZD9829: Plasma Concentration of total unconjugated warhead	Measurement of plasma concentration of total unconjugated warhead	Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.
Secondary	Pharmacokinetics of AZD9829: Area under the concentration time curve (AUC).	Area under the plasma concentration-time curve.	Module 1 - From date of first dose of AZD9829up until 30 days post last dose.
Secondary	Pharmacokinetics of AZD9829: Maximum plasma concentration of the study drug (Cmax).	Maximum observed plasma concentration of AZD9829.	Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.
Secondary	Pharmacokinetics of AZD9829: Time to maximum concentration (tmax)	Time to maximum observed plasma concentration of the study drug.	Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.
Secondary	Pharmacokinetics of AZD9829: Clearance	The volume of plasma from which the study drug is completely removed per unit time.	Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.
Secondary	Pharmacokinetics of AZD9829: Half-life (t 1/2)	Terminal elimination half-life.	Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.
Secondary	Pharmacokinetics of AZD9829: Anti-Drug Antibodies (ADA)	Evaluating the number of patients who develop anti-drug antibodies (ADA) during treatment.	Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.
Secondary	Pharmacokinetics of AZD9829: Anti-Drug Antibodies (ADA)	Evaluating the percentage of patients who develop anti-drug antibodies (ADA) during treatment.	Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.
Secondary	To determine the immunogenicity of AZD9829.	The number of participants who develop ADA (Anti Drug Antibodies).	Module 1 - From first dose to approximately 1 year.
Secondary	To determine the immunogenicity of AZD9829.	The percentage of participants who develop ADA (Anti Drug Antibodies).	Module 1 - From first dose to approximately 1 year.
Secondary	Overall Response Rate (ORR)	Overall response rate disease assessments in accordance with ELN2022 recommendations for AML and IWG2018 for MDS.	Module 1 - From first dose of AZD9829 until disease progression or end of the study (upto approximately 1 year)
Secondary	Composite Complete Response Rate (CCRR)	Composite CR rate disease assessment in accordance with ELN2022 for AML and IWG2018 for MDS.	Module 1 - From first dose of AZD9829 up to approximately 1 year.
Secondary	Complete remission with incomplete hematologic recovery (CRi)	The endpoint of complete remission with CRi as defined by ELN2022 criteria.	Module 1 - From first dose of AZD9829 up to approximately 1 year.
Secondary	Complete Response (CR)	Complete response (CR) according to ELN2022 for AML and IWG2018 for MDS.	Module 1 - From first dose of AZD9829 up to approximately 1 year.
Secondary	Duration of Response (DoR)	Time from first documented response until the date of relapse or death.	Module 1 -Time from first documented response until disease progression or death (approximately 1 year).
Secondary	Time to Response (TTR)	Time from first dose to the achievement of first overall response. Disease assessments will follow ELN2022 for AML and IWG2018 for MDS.	Module 1 - From first dose of AZD9829 until complete remission, disease progression or death (approximately 1 year).
Secondary	Time to Next Treatment (TTNT)	The time from the start of treatment date until the date of subsequent antileukemia therapy.	Module 1 - From first dose of AZD9829 until the date of subsequent anti-leukemia-therapy or death (approximately 1 year).
Secondary	Progression-free Survival (PFS)	The time from the start of treatment date until the date of disease progression or death.	Module 1 - From first dose of AZD9829 until disease progression or death (approximately 1 year).
Secondary	Overall Survival (OS)	The time from the start of treatment date until death.	Module 1 - From first dose of AZD9829 until death (approximately 1 year).
Secondary	Event-free Survival (EFS)	The time from the start of treatment date to disease progression, death, or initiation of a new anti-leukemic therapy.	Module 1 - From first dose of AZD9829 until disease progression, death, or initiation of a new anti-leukemic therapy (approximately 1 year).