Hematological Malignancies
Conditions
Keywords
AZD9829, Anti-cancer agents, Dose escalation
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.
Interventions
DRUGAZD9829
AZD9829 will be administered by IV infusion
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of dose limiting toxicities (DLTs). | Module 1 - 28 days. | DLTs are dose-limiting toxicities as defined in the study protocol. |
| Safety evaluation of AZD9829: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Module 1 - From informed consent until 60 days after last dose of AZD9829. | Frequency, severity and relationship to study drug of AEs and SAEs |
| Identify RP2D in R/R AML patients. | Moldule 1 -From informed consent until 60 days after last dose of AZD9829. | Incidence of AEs/SAEs and PK data |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of AZD9829: Plasma Concentration of total antibody | Module 1 - From date of first dose of AZD9829 up until 30 days post last dose. | Measurement of plasma concentration of conjugated and unconjugated antibody |
| Pharmacokinetics of AZD9829: Plasma Concentration of total unconjugated warhead | Module 1 - From date of first dose of AZD9829 up until 30 days post last dose. | Measurement of plasma concentration of total unconjugated warhead |
| Pharmacokinetics of AZD9829: Area under the concentration time curve (AUC). | Module 1 - From date of first dose of AZD9829up until 30 days post last dose. | Area under the plasma concentration-time curve. |
| Pharmacokinetics of AZD9829: Maximum plasma concentration of the study drug (Cmax). | Module 1 - From date of first dose of AZD9829 up until 30 days post last dose. | Maximum observed plasma concentration of AZD9829. |
| Pharmacokinetics of AZD9829: Time to maximum concentration (tmax) | Module 1 - From date of first dose of AZD9829 up until 30 days post last dose. | Time to maximum observed plasma concentration of the study drug. |
| Pharmacokinetics of AZD9829: Clearance | Module 1 - From date of first dose of AZD9829 up until 30 days post last dose. | The volume of plasma from which the study drug is completely removed per unit time. |
| Pharmacokinetics of AZD9829: Half-life (t 1/2) | Module 1 - From date of first dose of AZD9829 up until 30 days post last dose. | Terminal elimination half-life. |
| Pharmacokinetics of AZD9829: Anti-Drug Antibodies (ADA) | Module 1 - From date of first dose of AZD9829 up until 30 days post last dose. | Evaluating the number of patients who develop anti-drug antibodies (ADA) during treatment. |
| To determine the immunogenicity of AZD9829. | Module 1 - From first dose to the 30-Day SFU visit | The number of participants who develop ADA (Anti Drug Antibodies). |
| Overall Response Rate (ORR) | Module 1 - From first dose of AZD9829 until disease progression or end of the study (upto approximately 1 year) | Overall response rate disease assessments in accordance with ELN2022 recommendations for AML and IWG 2006/2018 for MDS. |
| Composite Complete Response Rate (CCRR) | Module 1 - From first dose of AZD9829 up to approximately 1 year. | Composite CR rate disease assessment in accordance with ELN2022 for AML and IWG 2006/2018 for MDS. |
| Complete remission with incomplete hematologic recovery (CRi) | Module 1 - From first dose of AZD9829 up to approximately 1 year. | The endpoint of complete remission with CRi as defined by ELN2022 criteria. |
| Complete Response (CR) | Module 1 - From first dose of AZD9829 up to approximately 1 year. | Complete response (CR) according to ELN2022 for AML and IWG 2006/2018 for MDS. |
| Duration of Response (DoR) | Module 1 -Time from first documented response until disease progression or death (approximately 1 year). | Time from first documented response until the date of relapse or death. |
| Time to Response (TTR) | Module 1 - From first dose of AZD9829 until complete remission, disease progression or death (approximately 1 year). | 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 to Next Treatment (TTNT) | Module 1 - From first dose of AZD9829 until the date of subsequent anti-leukemia-therapy or death (approximately 1 year). | The time from the start of treatment date until the date of subsequent antileukemia therapy. |
| Progression-free Survival (PFS) | Module 1 - From first dose of AZD9829 until disease progression or death (approximately 1 year). | The time from the start of treatment date until the date of disease progression or death. |
| Overall Survival (OS) | Module 1 - From first dose of AZD9829 until death (approximately 1 year). | The time from the start of treatment date until death. |
| Event-free Survival (EFS) | Module 1 - From first dose of AZD9829 until disease progression, death, or initiation of a new anti-leukemic therapy (approximately 1 year). | The time from the start of treatment date to disease progression, death, or initiation of a new anti-leukemic therapy. |
Countries
Australia, China, Germany, Italy, Japan, South Korea, Spain, Taiwan, United Kingdom, United States
Outcome results
None listed