A Phase 1b/2, Open-Label, Dose Escalation and Expansion Study Evaluating the Safety and Efficacy of Entospletinib (GS-9973) With Vincristine and Dexamethasone in Adult Subjects With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 30
- 试验地点
- 13
- 主要终点
- Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The primary objective of this study is to evaluate the safety of entospletinib in combination with vincristine (VCR), and dexamethasone (DEX) in adults with previously treated relapsed or refractory B-cell lineage acute lymphoblastic leukemia (ALL).
This is a dose escalation study in which after 2 induction cycles participants may be put on maintenance for up to 36 cycles if they have obtained clinical benefit from the treatment.
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
- •Adults with ALL in need of treatment
排除标准
- •Diagnosis of Burkitt's Leukemia, or lymphoid blast crisis of chronic myelogenous leukemia (CML)
- •History of myelodysplastic syndrome or solid organ transplantation
- •Prior allogeneic bone marrow progenitor cell transplant within 100 days or on active immunosuppression for graft versus host disease (GVHD) treatment or prophylaxis within 28 days prior to enrollment
- •Note: Other protocol defined Inclusion/ Exclusion criteria may apply.
研究组 & 干预措施
ENTO 200 mg + VCR 0.5 mg
Monotherapy Lead-In (Day -7 to Day -1): Entospletinib (ENTO) 200 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 200 mg twice daily continuously in combination with vincristine (VCR) 0.5 mg intravenously (IV) on Days 1, 8, 15, and 22 of each cycle; dexamethasone (DEX) 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and central nervous system (CNS) prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a complete remission (CR) received stem cell transplant (SCT) (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a partial response [PR]) after induction were offered maintenance therapy with ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
干预措施: Entospletinib (Drug)
ENTO 200 mg + VCR 0.5 mg
Monotherapy Lead-In (Day -7 to Day -1): Entospletinib (ENTO) 200 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 200 mg twice daily continuously in combination with vincristine (VCR) 0.5 mg intravenously (IV) on Days 1, 8, 15, and 22 of each cycle; dexamethasone (DEX) 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and central nervous system (CNS) prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a complete remission (CR) received stem cell transplant (SCT) (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a partial response [PR]) after induction were offered maintenance therapy with ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
干预措施: Vincristine (Drug)
ENTO 200 mg + VCR 0.5 mg
Monotherapy Lead-In (Day -7 to Day -1): Entospletinib (ENTO) 200 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 200 mg twice daily continuously in combination with vincristine (VCR) 0.5 mg intravenously (IV) on Days 1, 8, 15, and 22 of each cycle; dexamethasone (DEX) 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and central nervous system (CNS) prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a complete remission (CR) received stem cell transplant (SCT) (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a partial response [PR]) after induction were offered maintenance therapy with ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
干预措施: Dexamethasone (Drug)
ENTO 200 mg + VCR 0.5 mg
Monotherapy Lead-In (Day -7 to Day -1): Entospletinib (ENTO) 200 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 200 mg twice daily continuously in combination with vincristine (VCR) 0.5 mg intravenously (IV) on Days 1, 8, 15, and 22 of each cycle; dexamethasone (DEX) 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and central nervous system (CNS) prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a complete remission (CR) received stem cell transplant (SCT) (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a partial response [PR]) after induction were offered maintenance therapy with ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
干预措施: CNS Prophylaxis (Drug)
ENTO 400 mg + VCR 0.5 mg
Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
干预措施: Entospletinib (Drug)
ENTO 400 mg + VCR 0.5 mg
Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
干预措施: Vincristine (Drug)
ENTO 400 mg + VCR 0.5 mg
Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
干预措施: Dexamethasone (Drug)
ENTO 400 mg + VCR 0.5 mg
Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
干预措施: CNS Prophylaxis (Drug)
ENTO 400 mg + VCR 1.0 mg
Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
干预措施: Entospletinib (Drug)
ENTO 400 mg + VCR 1.0 mg
Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
干预措施: Vincristine (Drug)
ENTO 400 mg + VCR 1.0 mg
Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
干预措施: Dexamethasone (Drug)
ENTO 400 mg + VCR 1.0 mg
Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
干预措施: CNS Prophylaxis (Drug)
ENTO 400 mg + VCR 2.0 mg
Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
干预措施: Entospletinib (Drug)
ENTO 400 mg + VCR 2.0 mg
Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
干预措施: Vincristine (Drug)
ENTO 400 mg + VCR 2.0 mg
Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
干预措施: Dexamethasone (Drug)
ENTO 400 mg + VCR 2.0 mg
Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
干预措施: CNS Prophylaxis (Drug)
结局指标
主要结局
Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
时间窗: ENTO Lead-in and Cycle 1 (Day -7 through Day 28)
The occurrence of any of the following toxicities during Lead-in/Cycle 1 (Day -7 through Day 28) was considered a DLT if judged by the investigator to be possibly, probably, or definitely related to the administration of any drug in the treatment regimen (ENTO, VCR, DEX, institutional standard CNS prophylaxis): * Grade 4 (or higher) non-hematologic toxicity * Grade 3 non-hematologic toxicity lasting ≥ 7 days despite optimal supportive care * Any Grade 3 non-hematologic laboratory value if: * Medical intervention was required to treat, or * The abnormality led to hospitalization, or * The abnormality persisted for \> 1 week * Grade 4 Neutropenia (absolute neutrophil count \[ANC\] \< 500 /μL) persistent for greater than 14 days or associated with febrile neutropenia * Grade 4 thrombocytopenia (platelets \< 25,000/μL) persisting for greater than 14 days (or greater than 25,000 /μL, but requiring prophylactic platelet transfusion to maintain this level)
次要结局
- Percentage of Participants With Complete Remission (CR) at the End of Induction(End of Induction (Cycle 2, Day 28))
- Percentage of Participants With Overall Remission at the End of Induction(End of Induction (Cycle 2, Day 28))
- Percentage of Participants With Overall Response at the End of Induction(End of Induction (Cycle 2, Day 28))
- Percentage of Participants With Partial Response (PR) at the End of Induction(End of Induction (Cycle 2, Day 28))