Clinical trial NCT06179511: Study of AZD9829 in CD123+ Hematological Malignancies
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hematological Malignancies
Keywords: AZD9829
Anti-cancer agents
Dose escalation
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-12-22
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Frequency of dose limiting toxicities (DLTs).
timeFrame: Module 1 - 28 days.
measure: Safety evaluation of AZD9829: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Module 1 - From informed consent until 60 days after last dose of AZD9829.
measure: Identify RP2D in R/R AML patients.
timeFrame: Moldule 1 -From informed consent until 60 days after last dose of AZD9829.
Secondary outcomes:
measure: Pharmacokinetics of AZD9829: Plasma Concentration of total antibody
timeFrame: Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.
measure: Pharmacokinetics of AZD9829: Plasma Concentration of total unconjugated warhead
timeFrame: Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.
measure: Pharmacokinetics of AZD9829: Area under the concentration time curve (AUC).
timeFrame: Module 1 - From date of first dose of AZD9829up until 30 days post last dose.
measure: Pharmacokinetics of AZD9829: Maximum plasma concentration of the study drug (Cmax).
timeFrame: Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.
measure: Pharmacokinetics of AZD9829: Time to maximum concentration (tmax)
timeFrame: Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.
measure: Pharmacokinetics of AZD9829: Clearance
timeFrame: Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.
measure: Pharmacokinetics of AZD9829: Half-life (t 1/2)
timeFrame: Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.
measure: Pharmacokinetics of AZD9829: Anti-Drug Antibodies (ADA)
timeFrame: Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.
measure: Pharmacokinetics of AZD9829: Anti-Drug Antibodies (ADA)
timeFrame: Module 1 - From date of first dose of AZD9829 up until 30 days post last dose.
measure: To determine the immunogenicity of AZD9829.
timeFrame: Module 1 - From first dose to the 30-Day SFU visit
measure: To determine the immunogenicity of AZD9829.
timeFrame: Module 1 - From first dose to the 30-Day SFU visit
measure: Overall Response Rate (ORR)
timeFrame: Module 1 - From first dose of AZD9829 until disease progression or end of the study (upto approximately 1 year)
measure: Composite Complete Response Rate (CCRR)
timeFrame: Module 1 - From first dose of AZD9829 up to approximately 1 year.
measure: Complete remission with incomplete hematologic recovery (CRi)
timeFrame: Module 1 - From first dose of AZD9829 up to approximately 1 year.
measure: Complete Response (CR)
timeFrame: Module 1 - From first dose of AZD9829 up to approximately 1 year.
measure: Duration of Response (DoR)
timeFrame: Module 1 -Time from first documented response until disease progression or death (approximately 1 year).
measure: Time to Response (TTR)
timeFrame: Module 1 - From first dose of AZD9829 until complete remission, disease progression or death (approximately 1 year).
measure: Time to Next Treatment (TTNT)
timeFrame: Module 1 - From first dose of AZD9829 until the date of subsequent anti-leukemia-therapy or death (approximately 1 year).
measure: Progression-free Survival (PFS)
timeFrame: Module 1 - From first dose of AZD9829 until disease progression or death (approximately 1 year).
measure: Overall Survival (OS)
timeFrame: Module 1 - From first dose of AZD9829 until death (approximately 1 year).
measure: Event-free Survival (EFS)
timeFrame: Module 1 - From first dose of AZD9829 until disease progression, death, or initiation of a new anti-leukemic therapy (approximately 1 year).
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Research Site
state: California
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: New York
country: United States
facility: Research Site
state: New York
city: Chapel Hill
country: United States
facility: Research Site
state: North Carolina
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Houston
country: United States
facility: Research Site
state: Texas
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Heidelberg
country: Australia
facility: Research Site
city: Melbourne
country: Australia
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Yoshida-gun
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Salamanca
country: Spain
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
Study officials:
References: