A Phase 1 Dose Escalation, Open-Label Study of Venetoclax in Combination With Navitoclax and Chemotherapy in Subjects With Relapsed/Refractory Acute Lymphoblastic Leukemia or Relapsed/Refractory Lymphoblastic Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 69
- 试验地点
- 15
- 主要终点
- Tmax of Venetoclax + Navitoclax
研究概览
简要总结
This dose-escalating study is to determine the safety, pharmacokinetics, and preliminary efficacy of venetoclax in combination with navitoclax and chemotherapy in adult and pediatric participants with relapsed/refractory acute lymphoblastic leukemia (ALL) or relapsed/refractory lymphoblastic lymphoma. A safety expansion cohort of approximately 20 patients may be enrolled in addition to the 50 participants in dose-escalation cohort.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have relapsed or refractory acute lymphoblastic leukemia (ALL) or relapsed or refractory lymphoblastic lymphoma (LL). Refractory is defined as persistent disease after at least 2 courses of chemotherapy.
- •Participants with ALL with Philadelphia chromosome or with an ABL class targetable fusion are eligible.
- •Participants with LL must have radiographic evidence of disease
- •Participants <= 18 years of age who do not have a standard of care treatment option available.
- •Must weigh greater than or equal to 20 kg.
- •Must be able to swallow pills.
- •Must have adequate hepatic and kidney function.
- •Must have adequate performance status:
- •Participants less than or equal to 16 years of age: Lansky greater than or equal to 50
- •Participants greater than 16 years of age: Karnofsky greater than or equal to 50 or Eastern Cooperative Oncology Group (ECOG) less than 3.
排除标准
- •Participant has central nervous system (CNS) disease with cranial involvement that requires radiation.
- •Participants who are less than 100 days post-transplant, or greater than 100 days post-transplant with active graft versus host disease (GVHD), or are still continuing post-transplant immunosuppressant therapy within 7 days prior to the first dose of study drug.
- •Participants who have received any of the following prior to the first dose of study drug:
- •Inotuzumab within 30 days (if participant received inotuzumab > 30 days prior to Day 1, must have ALT, AST and bilirubin < ULN).
- •A biologic agent (i.e., monoclonal antibodies) for anti-neoplastic intent within 30 days
- •CAR-T infusion or other cellular therapy within 30 days
- •Any anti-cancer therapy including blinatumomab, chemotherapy, radiation therapy targeted small molecule agents or investigational agents within 14 days, or 5 half-lives, whichever is shorter
- •Exception: Philadelphia Chromosome (Ph)+ ALL subjects on TKIs at Screening may enroll and remain on Tyrosine Kinase Inhibitor (TKI) therapy to control disease. Participants on venetoclax at screening may enroll and remain on venetoclax.
- •Steroid therapy for anti-neoplastic intent within 5 days
- •Hydroxyurea that is ongoing (hydroxyurea is permitted up to the first dose)
- •A strong or moderate CYP3A inhibitor or inducer within 7 days
- •Aspirin within 7 days, or 5 half-lives, whichever is longer
- •An excluded antiplatelet/anticoagulant drug or a herbal supplement that affects platelet function within 7 days, or 5 half-lives, whichever is longer
- •Participants with malabsorption syndrome or any other condition that precludes enteral administration.
研究组 & 干预措施
Venetoclax + Navitoclax + Chemotherapy
Venetoclax weight-adjusted doses administered orally every day (QD) starting on Day 1 + navitoclax various, weight-adjusted doses administered orally QD starting on Day 3 + chemotherapy (peg-asparaginase [or any other forms of asparaginase], vincristine, dexamethasone) and tyrosine kinase inhibitor [TKI, if applicable]). This regimen and any of its components may be delayed, reduced or omitted at the discretion of the Investigator.
干预措施: Navitoclax (Drug)
Venetoclax + Navitoclax + Chemotherapy
Venetoclax weight-adjusted doses administered orally every day (QD) starting on Day 1 + navitoclax various, weight-adjusted doses administered orally QD starting on Day 3 + chemotherapy (peg-asparaginase [or any other forms of asparaginase], vincristine, dexamethasone) and tyrosine kinase inhibitor [TKI, if applicable]). This regimen and any of its components may be delayed, reduced or omitted at the discretion of the Investigator.
干预措施: Chemotherapy (Drug)
Venetoclax + Navitoclax + Chemotherapy
Venetoclax weight-adjusted doses administered orally every day (QD) starting on Day 1 + navitoclax various, weight-adjusted doses administered orally QD starting on Day 3 + chemotherapy (peg-asparaginase [or any other forms of asparaginase], vincristine, dexamethasone) and tyrosine kinase inhibitor [TKI, if applicable]). This regimen and any of its components may be delayed, reduced or omitted at the discretion of the Investigator.
干预措施: Venetoclax (Drug)
结局指标
主要结局
Tmax of Venetoclax + Navitoclax
时间窗: Up to approximately 9 months
Time to Cmax (Tmax) of Venetoclax + Navitoclax
Cmax of Venetoclax + Navitoclax
时间窗: Up to approximately 9 months
Maximum observed plasma concentration (Cmax) of venetoclax + navitoclax
CL/F of Venetoclax + Navitoclax
时间窗: Up to approximately 9 months
Apparent oral clearance (CL/F) of venetoclax + navitoclax
Number of participants with dose-limiting toxicities (DLT)
时间窗: Up to approximately 28 days after initial dose of study drug
A DLT is any Grade 3 or higher non-hematologic adverse event (AE) with exceptions outlined in the protocol. AEs and toxicities that occur beyond the DLT assessment period will also be evaluated by the investigator and AbbVie and may be considered as dose-limiting.
AUC of Venetoclax + Navitoclax
时间窗: Up to approximately 9 months
Area under the plasma concentration-time curve (AUC) of venetoclax + navitoclax
次要结局
- Number of Participant who Proceed to Stem Cell Transplantation or Chimeric antigen receptor T-cell (CAR-T) Therapy(Up to 9 months after the last subject has enrolled into the study)
- Progression-free survival (PFS)(Up to 9 months after the last subject has enrolled into the study)
- Partial Response (PR) rate(Up to 9 months after the last subject has enrolled into the study)
- Overall survival (OS)(Up to 9 months after the last subject has enrolled into the study)
- Objective response rate (ORR)(Up to 9 months after the last subject has enrolled into the study)
- Complete Response (CR) rate(Up to 9 months after the last subject has enrolled into the study)