B-cell Acute Lymphoblastic Leukemia (B-ALL)
Conditions
Interventions
Patients will receive AZD4512 as monotherapy via intravenous infusion. AZD4512 is an antibody-drug conjugate targeting CD22.
Sponsors
Hibi Kazushige
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age: - 16 years old or older in Module 1 (US only: >=18year) - 12 years old or older in Module 2 2. Diagnosis: Known Diagnosis of CD22-positive B-ALL based on criteria established by WHO (Alaggio et al. 2022). - Participants must have relapsed or refractory B-ALL ('relapsed' defined as bone marrow blasts > 5% or reappearance of blasts in PB) - Module 1 (DE): Ph(-) B-ALL and Ph(+) B-ALL - R/R - Backfill of Module 1 and Module 2 (DO): R/R Ph(-) B-ALL 3. Performance status (ECOG = 50; LPS >= 50) 4. Peripheral lymphoblast count 4 weeks, prior cell therapy or autoHSCT >8 weeks, alloHSCT >12 weeks
Exclusion criteria
Exclusion criteria: 1. Burkitt lymphoma and leukemia 2. Isolated extramedullary disease; Active testicular or CNS (> CNS1) involvement 3. Unresolved non-heme toxicities Grade >= 2 (except alopecia, stable Grade <= 2 neuropathy, vitiligo, endocrine disorders controlled with therapy) 4. History of drug-induced non-infectious ILD/pneumonitis requiring oral or IV steroids or supplemental oxygen or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening 5. Prior/concomitant therapy - Cytotoxic treatment within 14 days (except ALL maintenance medications or cytoreduction) - Biologic (immuno-oncology) treatment within 28 days or 5 half-lives (whichever is shorter) - Non-CNS radiation within 2 weeks & CNS radiation within 4 weeks - Medications known to prolong QTc and/or associated with Torsades de Pointes within 5 half-lives - Strong inhibitors of CYP 3A within 14 days or 5 half-lives (whichever is longer) - Investigational agents or study interventions in the last 30 days or 5 half-lives prior to the first dose of AZD4512 whichever is longer. If the investigational product is an agent to treat B-ALL and meets the modality criteria, then a specific washout period must be adhered to instead.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mdule 1 (Dose Escalation): -Number of participants with dose-limiting toxicities (DLTs). [Time Frame: From first dose up to 21 days (DLT period).] -Frequency, duration and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs). [Time Frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)] -Frequency of dose interruptions, modifications, delays, and discontinuations due to AEs. [Time Frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)] -Number of participants with clinically significant changes in laboratory values, ECGs, performance status, and vital signs [Time Frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)] Module 2 (Dose Optimization): -Overall response rate (ORR) in participants with R/R Ph(-) B-ALL [Time Frame: From date of first dose of AZD4512 up until end of study, up to 38 months]-Frequency, duration and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs) -Frequency, duration and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs) [Time Frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)] Assessed by the CTCAE criteria version 5.0 -Frequency of dose interruptions, modifications, delays, and discontinuations due to AEs [Time Frame: Number of participants with clinically significant changes in laboratory values, ECGs, performance status, and vital signs [Time Frame: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)] | — |
Countries
Australia, Canada, China, Japan, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactKazushige Hibi
Astrazeneka K.K
Outcome results
None listed