跳至主要内容
MedPath Trial logoMedPath TrialMedPath Trial Home
临床试验/NCT07109219
NCT07109219招募中1 期

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

AstraZeneca26 个研究点 分布在 9 个国家目标入组 83 人开始时间: 2025年11月12日最近更新:
Share to TwitterShare to FacebookShare to LinkedInShare to Reddit
干预措施

试验速览

阶段
1 期
状态
招募中
发起方
AstraZeneca
入组人数
83
试验地点
26
主要终点
Module 1 (Dose Escalation): Number of participants with dose-limiting toxicities (DLTs).
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The study is intended to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of AZD4512 in patients with relapsed/refractory B-Cell acute lymphoblastic leukemia (r/r B-ALL).

详细描述

In this Phase I/II, open-label multi-center study AZD4512 will be administered to adult/young adult patients (Module 1: >=16 years; Module 2: >=12 years) with relapsed/refractory B-Cell acute lymphoblastic leukemia (B-ALL). This study will have 2 parts: Module 1 - Dose Escalation and Module 2 - Dose Optimization.

研究设计

研究类型
Interventional
分配方式
Non Randomized
干预模型
Sequential
主要目的
Treatment
盲法
None

入排标准

年龄范围
12 Years 至 —（Child, Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •16 years old in Module 1 (US only: ≥18year)
  • •12 years old 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 ≤ 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. Participants who have received prior CD22 targeted therapies are eligible.
  • •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

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 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.

研究组 & 干预措施

Module 1 Dose Escalation

Experimental

Module 1 will evaluate escalating doses of AZD4512 as monotherapy to determine the maximum tolerated dose (MTD) and/or doses of AZD4512 for subsequent evaluation in Module 2 (dose optimization), in participants with relapsed/refractory (R/R) Philadelphia chromosome positive (Ph[+]) and negative (Ph[-]) B-ALL, R/R as defined by National Comprehensive Cancer Network (NCCN) guidelines.

干预措施: AZD4512 monotherapy (Combination Product)

Module 2 Dose Optimization

Experimental

Module 2 will randomize participants with R/R (as defined by NCCN guidelines) Ph(-) BALL only across 2 to 3 dose levels identified in Module 1 to receive AZD4512 monotherapy for further exploration of the doses. The aim of Module 2 is to identify the recommended Phase 2 dose (RP2D) of AZD4512 monotherapy, evaluate the efficacy and further define the safety profile of AZD4512.

干预措施: AZD4512 monotherapy (Combination Product)

结局指标

主要结局

Module 1 (Dose Escalation): Number of participants with dose-limiting toxicities (DLTs).

时间窗: From first dose up to 21 days (DLT period).

DLTs are dose-limiting toxicities as defined in the study protocol.

Module 1 (Dose Escalation): Frequency, duration and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs)

时间窗: 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

Module 1 (Dose Escalation): Frequency of dose interruptions, modifications, delays, and discontinuations due to AEs

时间窗: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

Module 1 (Dose Escalation): Number of participants with clinically significant changes in laboratory values, ECGs, performance status, and vital signs

时间窗: 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

时间窗: From date of first dose of AZD4512 up until end of study, up to 38 months

To evaluate the efficacy based on NCCN response criteria, measured by ORR (CR/CRh)

Module 2 (Dose Optimization): Frequency, duration and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs)

时间窗: 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

Module 2 (Dose Optimization): Frequency of dose interruptions, modifications, delays, and discontinuations due to AEs

时间窗: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

Module 2 (Dose Optimization): Number of participants with clinically significant changes in laboratory values, ECGs, performance status, and vital signs

时间窗: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

次要结局

  • Module 1 (Dose Escalation): Objective Response Rate (ORR): proportion of participants with CR or CRh(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 1 (Dose Escalation): Composite Complete Remission (CRc) rate: proportion of participants with CR, CRh, or CRi(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 1 (Dose Escalation): Complete Remission (CR) rate(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 1 (Dose Escalation): Time to Response (TTR)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 1 (Dose Escalation): Duration of Response (DoR)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 1 (Dose Escalation): Event-Free Survival (EFS)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 1 (Dose Escalation): Overall Survival (OS)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 1 (Dose Escalation): Percentage of participants who receive subsequent allogeneic hematopoietic stem cell transplant (HSCT)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 2 (Dose Optimization): Complete Remission (CR) rate(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 2 (Dose Optimization):Composite Complete Remission (CRc) rate: proportion of participants with CR, CRh, or CRi(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 2 (Dose Optimization):Time to Response (TTR)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 2 (Dose Optimization): Duration of Response (DoR)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 2 (Dose Optimization):Event-Free Survival (EFS)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 2 (Dose Optimization): Overall Survival (OS)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 2 (Dose Optimization): Percentage of participants who receive subsequent allogeneic hematopoietic stem cell transplant (HSCT)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 2 (Dose Optimization): MRD-negative CR rate, CR/CRh (ORR), CR/CRi/CRh (CRc) rate(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 2 (Dose Optimization): Plasma PK parameters of AZD4512(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 2 (Dose Optimization): total antibody and total unconjugated payload(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 2 (Dose Optimization): Area Under Curve (AUC)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 2 (Dose Optimzation): Peak Plasma Concentration (Cmax)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 2 (Dose Optimization): Time to max concentration (Tmax)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 2 (Dose Optimization): Half life (T1/2)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 2 (Dose Optimization): Clearance (CL)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 2 (Dose Optimization): Volume of distribution (Vz)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 2 (Dose Optimization): Summary of of pre-existing and treatment induced ADAs for AZD4512 (positive or negative, titers)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 1 (Dose Escalation): Volume of distribution (Vz)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 1 (Dose Escalation): Number and percentage of participants who develop anti-drug antibodies (ADAs)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 1 (Dose Escalation): Plasma PK parameters of AZD4512(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 1 (Dose Escalation): Total antibody and total unconjugated payload(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 1 (Dose Escalation): Area Under Curve (AUC)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 1 (Dose Escalation): Peak Plasma Concentration (Cmax)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 1 (Dose Escalation): Time to max concentration (Tmax)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 1 (Dose Escalation): Half life (T1/2)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 1 (Dose Escalation): Clearance (CL)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 2 (Dose Optimzation): Peak Plasma Concentration (Cmax)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 1 (Dose Escalation): Plasma PK parameters of AZD4512(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 1 (Dose Escalation): Total antibody and total unconjugated payload(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 1 (Dose Escalation): Area Under Curve (AUC)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 1 (Dose Escalation): Peak Plasma Concentration (Cmax)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 1 (Dose Escalation): Time to max concentration (Tmax)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 1 (Dose Escalation): Half life (T1/2)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 1 (Dose Escalation): Clearance (CL)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 1 (Dose Escalation): Volume of distribution (Vz)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 1 (Dose Escalation): Number and percentage of participants who develop anti-drug antibodies (ADAs)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 1 (Dose Escalation): Objective Response Rate (ORR): proportion of participants with CR or CRh(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 1 (Dose Escalation): Composite Complete Remission (CRc) rate: proportion of participants with CR, CRh, or CRi(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 1 (Dose Escalation): Complete Remission (CR) rate(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 1 (Dose Escalation): Time to Response (TTR)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 1 (Dose Escalation): Duration of Response (DoR)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 1 (Dose Escalation): Event-Free Survival (EFS)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 1 (Dose Escalation): Overall Survival (OS)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 1 (Dose Escalation): Percentage of participants who receive subsequent allogeneic hematopoietic stem cell transplant (HSCT)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 2 (Dose Optimization): Complete Remission (CR) rate(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 2 (Dose Optimization):Composite Complete Remission (CRc) rate: proportion of participants with CR, CRh, or CRi(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 2 (Dose Optimization):Time to Response (TTR)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 2 (Dose Optimization): Duration of Response (DoR)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 2 (Dose Optimization):Event-Free Survival (EFS)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 2 (Dose Optimization): Overall Survival (OS)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 2 (Dose Optimization): Percentage of participants who receive subsequent allogeneic hematopoietic stem cell transplant (HSCT)(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 2 (Dose Optimization): MRD-negative CR rate, CR/CRh (ORR), CR/CRi/CRh (CRc) rate(From date of first dose of AZD4512 up until end of study, up to 38 months)
  • Module 2 (Dose Optimization): Plasma PK parameters of AZD4512(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 2 (Dose Optimization): total antibody and total unconjugated payload(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 2 (Dose Optimization): Area Under Curve (AUC)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 2 (Dose Optimization): Time to max concentration (Tmax)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 2 (Dose Optimization): Half life (T1/2)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 2 (Dose Optimization): Clearance (CL)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 2 (Dose Optimization): Volume of distribution (Vz)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))
  • Module 2 (Dose Optimization): Summary of of pre-existing and treatment induced ADAs for AZD4512 (positive or negative, titers)(From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months))

研究者

发起方
AstraZeneca
申办方类型
Industry
责任方
Sponsor

研究点 (26)

Loading locations...

相似试验

终止
1 期
Study of AZD0466 Monotherapy or in Combination in Patients With Advanced Haematological MalignanciesHaematological Malignancies
NCT04865419AstraZeneca46
招募中
1 期
Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid MalignanciesAdvanced Solid Malignancies
NCT05417594AstraZeneca695
已完成
1 期
Safety and Preliminary Efficacy Assessment of AZD7789 in Patients With Relapsed or Refractory Classical Hodgkin LymphomaRelapsed or Refractory Classical Hodgkin Lymphoma
NCT05216835AstraZeneca45
进行中（未招募）
1 期
Study of AZD5305 When Given in Combination With New Hormonal Agents in Patients With Metastatic Prostate CancerMetastatic Prostate Cancer
NCT05367440AstraZeneca174
招募中
1 期
A Trial of SHR-7787 Injection in Patients With Advanced Solid TumorsAdvanced Solid Tumors
NCT06605222Shanghai Hengrui Pharmaceutical Co., Ltd.201