Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia
Conditions
Interventions
- Experimental: Part A: AZD0486 Dose Escalation
Ascending dose level cohorts of AZD0486 in B-ALL participants aged 12 years and above.
Drug: AZD0486
Investigational Product administered via intravenou
Sponsors
Hibi Kazushige
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age: 12 years and above (Parts A, B and C). - Participants with B-cell Acute Lymphoblastic Leukemia with CD19 expression by local lab with: 1. Bone marrow infiltration with or more 5% blasts 2. Either relapsed or refractory after a minimum of 2 prior therapies or after 1 prior line of therapy if no SOC available option. 3. Philadelphia positive participants are allowed in all parts of the study if intolerant or refractory to TKIs. - For participants older than 16 years, Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2. For Participants 16 years or younger, Lansky score more or equal to 50%. The above is a summary, other inclusion criteria details may apply.
Exclusion criteria
Exclusion criteria: - Active CNS involvement by B-ALL, defined by presence of ALL blasts in CSF (CNS2 and CNS3 criteria). - Isolated extramedullary disease relapse. - Testicular leukemia - History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis; or prior Grade 4 neurotoxicity with CAR-T or TCE therapy. - History of other malignancy (with certain exceptions). - Unresolved AEs >/= Grade 2, from prior therapies - Prior therapy with TCEs within 4 weeks, CAR T-cell therapy or autologous HSCT within 8 we eks or prior alloSCT within 12 weeks of start of therapy. - GVHD requiring immunosuppressive therapy within 3 weeks prior to AZD0486 treatment. The above is a summary, other exclusion criteria details may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Part A: Frequency of DLTs DLTs are dose-limiting toxicities as defined in the study protocol. [Time Frame: 28 days] - Parts A & B: Safety Evaluation of AZD0486 Frequency, severity, and relationship to study drug of AEs and SAEs; dose modifications; changes in laboratory evaluations; QTc, and vital signs changes. [Time Frame: From signing of informed consent through completion of study treatment, an average of 6 months] - Parts B & C: Overall Response Rate (ORR) The Primary analysis for ORR be conducted in RP2D-treated participants (in Part B and C). [Time Frame: From First dose to end of treatment or data cutoff, whichever comes first, assessed up to 24 months] | — |
Countries
Australia, Canada, China, France, Germany, Italy, Japan, South Korea, Spain, Taiwan, United Kingdom, United States of America
Contacts
Public ContactKazushige Hibi
Astrazeneka K.K
Outcome results
None listed