A modular Phase I/II, open-label, multi-center study to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary efficacy of AZD4512 monotherapy or in combination with anticancer agent(s) in participants with Acute Lymphoblastic Leukemia
ESTADO CLÍNICO
Reclutando
FASE/S DEL ENSAYO
Fase I-II
PATOLOGÍA
Leucemia mieloide aguda, Linfoma, Leucemia
FECHA DE APERTURA
Noviembre, 2025
FECHA DE CIERRE
,
CRITERIOS DE INCLUSIÓN
1. Age: 16 years old in Module 1 (US only: 18year) 12 years old in Module 2
2. Diagnosis: Diagnosis of B-ALL WHO (WHO-HAEM5) 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 (BM blasts >5%)
3. Performance status (ECOG 2; KPS 50; LPS 50)
4. Peripheral lymphoblast count < 10,000/µL (may receive cytoreduction prior to C1D1 per protocol-specified criteria)
5. At least 2 prior therapies with refractoriness or relapse, or 1 prior therapy with refractoriness or relapse and no standard options available -Ph+ B-ALL (Module 1 DE only): intolerant to or have contraindications to TKI therapy or R/R disease despite treatment with at least 2 prior TKIs or at least one 3rd generation TKI
6. Prior DLI >4 weeks, prior cell therapy or autoHSCT >8 weeks, alloHSCT >12 weeks
2. Diagnosis: Diagnosis of B-ALL WHO (WHO-HAEM5) 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 (BM blasts >5%)
3. Performance status (ECOG 2; KPS 50; LPS 50)
4. Peripheral lymphoblast count < 10,000/µL (may receive cytoreduction prior to C1D1 per protocol-specified criteria)
5. At least 2 prior therapies with refractoriness or relapse, or 1 prior therapy with refractoriness or relapse and no standard options available -Ph+ B-ALL (Module 1 DE only): intolerant to or have contraindications to TKI therapy or R/R disease despite treatment with at least 2 prior TKIs or at least one 3rd generation TKI
6. Prior DLI >4 weeks, prior cell therapy or autoHSCT >8 weeks, alloHSCT >12 weeks
CRITERIOS DE EXCLUSIÓN
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 3A4 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.
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 3A4 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.
DESCRIPCIÓN
Module 1 Dose Escalation: To assess the safety and tolerability of AZD4512 in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines Module 1 Dose Escalation: To identify the MTD and/or doses of AZD4512 for subsequent evaluation in Module 2 Module 2 Dose Optimization:To evaluate the efficacy and determine the RP2D of AZD4512 in participants with R/R Ph(-) B-ALL based on NCCN response criteria Module 2 Dose Optimization: To assess the safety and tolerability of AZD4512 in participants with R/R Ph(-) B-ALL
PALABRAS CLAVE
acute lymphoblastic leukemia, leukemia
