A Phase 1b Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Entospletinib (ENTO) as Monotherapy in Japanese Subjects With Relapsed or Refractory Hematologic Malignancies and in Combination With Chemotherapy in Japanese Subjects With Previously Untreated Acute Myeloid Leukemia (AML)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 6
- 主要终点
- Percentage of Participants With Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT)
研究概览
简要总结
The primary objective of this study is to evaluate the safety and tolerability of entospletinib (ENTO) monotherapy and in combination with chemotherapy in Japanese participants.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ENTO monotherapy (Group A): relapsed or refractory hematologic malignancies by World Health Organisation (WHO) criteria and who are not eligible to receive standard of care
- •ENTO + cytarabine + daunorubicin (Group B): previously untreated AML by WHO criteria, who are deemed fit for cytarabine and daunorubicin (7+3) induction chemotherapy and are able to undergo up to 2 cycles of induction chemotherapy, as determined by the treating physician
- •Must have been born in Japan and must not have lived outside of Japan for a period > 1 year in the 5 years prior to Day 1 of study treatment
- •Must be able to confirm the Japanese origin of their maternal and paternal ancestry
排除标准
- •Known active central nervous system or leptomeningeal leukemic involvement
- •Ongoing liver injury, or known infection with chronic active hepatitis C virus (HCV) or chronic active hepatitis B virus (HBV)
- •NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
研究组 & 干预措施
ENTO monotherapy (Group A)
Participants with relapsed or refractory hematologic malignancies will receive ENTO twice daily of every 28-day cycle until participants meet treatment discontinuation criteria or do not experience clinical benefit.
干预措施: Entospletinib (Drug)
ENTO + cytarabine + daunorubicin (Group B)
Lead-in (Cycle 0): Participants with previously untreated AML will receive ENTO twice daily for 14 days.
Induction (Up to 2 cycles): ENTO in combination with daunorubicin and cytarabine for up to two 28-day cycles.
Post-remission chemotherapy (at least 2 cycles, up to 4 cycles): Some participants (who have achieved complete remission [CR] or morphologic complete remission with incomplete blood count recovery [CRi] and do not require or cannot proceed to allogeneic stem cell transplantation [SCT] and participants who are awaiting a donor or transitioning to allogeneic SCT per investigator discretion) will have the option to receive post-remission chemotherapy with ENTO twice daily in combination with high-dose cytarabine (Hi-DAC) for up to four 28-day cycles.
干预措施: Entospletinib (Drug)
ENTO + cytarabine + daunorubicin (Group B)
Lead-in (Cycle 0): Participants with previously untreated AML will receive ENTO twice daily for 14 days.
Induction (Up to 2 cycles): ENTO in combination with daunorubicin and cytarabine for up to two 28-day cycles.
Post-remission chemotherapy (at least 2 cycles, up to 4 cycles): Some participants (who have achieved complete remission [CR] or morphologic complete remission with incomplete blood count recovery [CRi] and do not require or cannot proceed to allogeneic stem cell transplantation [SCT] and participants who are awaiting a donor or transitioning to allogeneic SCT per investigator discretion) will have the option to receive post-remission chemotherapy with ENTO twice daily in combination with high-dose cytarabine (Hi-DAC) for up to four 28-day cycles.
干预措施: Daunorubicin (Drug)
ENTO + cytarabine + daunorubicin (Group B)
Lead-in (Cycle 0): Participants with previously untreated AML will receive ENTO twice daily for 14 days.
Induction (Up to 2 cycles): ENTO in combination with daunorubicin and cytarabine for up to two 28-day cycles.
Post-remission chemotherapy (at least 2 cycles, up to 4 cycles): Some participants (who have achieved complete remission [CR] or morphologic complete remission with incomplete blood count recovery [CRi] and do not require or cannot proceed to allogeneic stem cell transplantation [SCT] and participants who are awaiting a donor or transitioning to allogeneic SCT per investigator discretion) will have the option to receive post-remission chemotherapy with ENTO twice daily in combination with high-dose cytarabine (Hi-DAC) for up to four 28-day cycles.
干预措施: Cytarabine (Drug)
结局指标
主要结局
Percentage of Participants With Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT)
时间窗: Cycle 1 (28-day cycle)
Occurrence of any of the following toxicities, attributable to ENTO, during Cycle 1 was considered DLT: * Grade 4 non-hematologic toxicity except alopecia, nausea, and vomiting controllable with anti-emetic therapy, line associated venous thrombosis, infection-related toxicities such as fever/sepsis, and fatigue. * In participants without bone marrow evidence of hematologic malignancy, hematologic toxicity defined as failure to recover absolute neutrophil count (ANC \> 500/μL) or platelet count (\>25000/μL) within 28 days * Grade 4, clinically significant, electrolyte abnormalities that were not correctable within 24 hours * Liver function test abnormalities that did not resolve to Grade 2 within 10 days * Infection that resulted from unexpectedly complicated prolonged myelosuppression * Toxicities that required temporary interruption of treatment and did not resolve to Grade 2 within 10 days or ENTO was suspended or dose reduced for a period of more than 10 days.
次要结局
- Percentage of Participants With AEs and Laboratory Abnormalities Not Defined as DLT(Day 1 Up to 30 days after permanent discontinuation of study treatment (maximum approximately 80 weeks))
- Plasma Concentration of ENTO(Cycle 1 (28-days cycle) Day 8 at 0 (predose), 1, 2, 3, 4, 6, 8, and 12 hours postdose)