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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 13
- 试验地点
- 4
- 主要终点
- Module 1 Dose Escalation: Determine the MTD and/or doses to explore in Module 2
研究概览
简要总结
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
研究设计
- 分配方式
- Randomized
- 主要目的
- Module 2 Dose Optimization
- 盲法
- None
入排标准
- 年龄范围
- 0 years 至 65+ years（0-17 Years, 65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Age: ≥ 16 years old in Module 1 ≥ 12 years old in Module 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%)
- •Performance status (ECOG ≤ 2; KPS ≥ 50; LPS ≥ 50)
- •Peripheral lymphoblast count < 10,000/µL (may receive cytoreduction prior to C1D1 per protocol-specified criteria)
- •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
- •Prior DLI >4 weeks, prior cell therapy or autoHSCT >8 weeks, alloHSCT >12 weeks
排除标准
- •Burkitt lymphoma and leukemia
- •Isolated extramedullary disease; Active testicular or CNS (> CNS1) involvement
- •Unresolved non-heme toxicities Grade ≥ 2 (except alopecia, stable Grade ≤ 2 neuropathy, vitiligo, endocrine disorders controlled with therapy)
- •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
- •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 21 days or 5 half-lives (whichever is longer) -Strong inhibitors of CYP 3A4 within 21 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
结局指标
主要结局
Module 1 Dose Escalation: Determine the MTD and/or doses to explore in Module 2
Module 1 Dose Escalation: Determine the MTD and/or doses to explore in Module 2
Module 1 Dose Escalation: Safety and Tolerability of AZD4512 -Assessment of DLT -Assessment of TEAEs/TRAEs/SAEs -Interruptions, modifications, delays and discontinuations -Clinically significant changes from baseline
Module 1 Dose Escalation: Safety and Tolerability of AZD4512 -Assessment of DLT -Assessment of TEAEs/TRAEs/SAEs -Interruptions, modifications, delays and discontinuations -Clinically significant changes from baseline
Module 2 Dose Optimization: Antitumour activity and determine the RP2D of AZD4512 -Response Rate: ORR (CR/CRh)
Module 2 Dose Optimization: Antitumour activity and determine the RP2D of AZD4512 -Response Rate: ORR (CR/CRh)
Module 2 Dose Optimization:Safety and Tolerability of AZD4512 -Assessment of TEAEs/TRAEs/SAEs -Interruptions, modifications, delays and discontinuations -Clinically significant changes from baseline
Module 2 Dose Optimization:Safety and Tolerability of AZD4512 -Assessment of TEAEs/TRAEs/SAEs -Interruptions, modifications, delays and discontinuations -Clinically significant changes from baseline
次要结局
- Module 1 Dose Escalation: Characterize AZD4512 PK as monotherapy
- Module 1 Dose Escalation: Immunogenicity as monotherapy -ADA development
- Module 1 Dose Escalation: Preliminary Antitumour Activity of AZD4512 -Response Rate: ORR (CR/CRh), CR and CRc rate, TTR, DoR, EFS, OS, subsequent HSCT
- Module 2 Dose Optimization: Antitumour Activity of AZD4512 -Response Rate: CR and CRc rate, TTR, DoR, EFS, OS, subsequent HSCT
- Module 2 Dose Optimization: Effect of AZD4512 on MRD (NGS) -MRD-negative CR rate, CR/CRh (ORR), CRc (CR/CRi/CRh) rate
- Module 2 Dose Optimization: PK of AZD4512 as monotherapy
- Module 2 Dose Optimization: Immunogenicity as monotherapy -ADA development
研究者
AstraZeneca Clinical Study Information Center
Scientific
AstraZeneca AB