Open-label, Single-arm Trial to Evaluate Antitumor Activity, Safety, and Pharmacokinetics of Isatuximab Used in Combination With Chemotherapy in Pediatric Patients From 28 Days to Less Than 18 Years of Age With Relapsed/Refractory B or T Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia in First or Second Relapse
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Sanofi
- 入组人数
- 67
- 试验地点
- 41
- 主要终点
- Percentage of Participants With Complete Response (CR) Rate
研究概览
简要总结
Primary Objective:
Evaluate the anti-leukemic activity of isatuximab in combination with standard chemotherapies in pediatric participants of ages 28 days to less than 18 years with Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) or Acute Myeloid Leukemia (AML)
Secondary Objectives:
- Safety and tolerability assessments
- Assessment of infusion reactions (IRs)
- Pharmacokinetics (PK) of isatuximab
- Minimal residual disease
- Overall response rate
- Overall survival
- Event free survival
- Duration of response
- Relationship between clinical effects and CD38 receptor density and occupancy
详细描述
The study included:
- a screening period of up to (up to 3 weeks prior to the first study treatment administration);
- a study treatment period [Day 1 to Day 57 for Acute Lymphoblastic Leukemia (ALL); Day 1 to Day 22 for Acute Myeloid Leukemia (AML)];
- the period of aplasia followed by a recovery period;
- an end of treatment (EOT) visit [within 30 days after hematological recovery;
- a follow-up period (until final analysis cut off date).
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
- 28 Days 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.
干预措施: Isatuximab (Drug)
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.
干预措施: Dexamethasone or equivalent (Drug)
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.
干预措施: Fludarabine (Drug)
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.
干预措施: Cytarabine (Drug)
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.
干预措施: Liposomal daunorubicin (Drug)
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.
干预措施: Daunorubicin (nonliposomal) (Drug)
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.
干预措施: Idarubicin (Drug)
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.
干预措施: Filgrastim or equivalent (Drug)
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.
干预措施: Mitoxantrone (Drug)
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.
干预措施: Doxorubicin (Drug)
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.
干预措施: Vincristine (Drug)
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.
干预措施: Pegaspargase (PEG) Asparaginase (Drug)
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.
干预措施: Cyclophosphamide (Drug)
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.
干预措施: Etoposide (Drug)
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.
干预措施: Methotrexate (Drug)
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.
干预措施: L - Asparginase (Drug)
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.
干预措施: Hydroxyurea (Drug)
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.
干预措施: L - Asparaginase (Erwinase) (Drug)
结局指标
主要结局
Percentage of Participants With Complete Response (CR) Rate
时间窗: From enrollment until the primary analysis completion date of 12 Sep 2022; the median duration of exposure was approximately 7 weeks
The complete response rate (CR + CRi \[complete response with incomplete peripheral recovery\]) was defined as the percentage of participants achieving complete response (CR + CRi) assessed by the investigator per National Comprehensive Cancer Network (NCCN) guidelines version 1.2018 criteria. CR was defined as \<5% blasts in a bone marrow aspirate (BMA) with spicules; no circulating blasts (ALL)/no blasts with Auer rods (AML) or extramedullary disease, no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/central nervous system involvement (ALL), trilineage hematopoiesis (ALL); Absolute neutrophil count (ANC) \>=1000/microliter (mcL); platelets \>100000/mcL; red blood cell transfusion independence. If the physician documented transfusion dependency related to study treatment and not to the participant's underlying disease, CRi was reported. CRi met the same criteria as for CR, except neutrophils and/or platelets recovery (ANC \<1000/mcL or platelets \<100000/mcL).
次要结局
- AML: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough)(Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 2 Day 15)
- Event-Free Survival (EFS)(From study treatment administration up to the date of first documented disease progression or death due to any cause, a maximum of 45 months)
- AML: AUC of Isatuximab(From Week 0 to Week 1, Week 0 to Week 3, and Week 0 to Week 8)
- Cluster of Differentiation (CD)38 Receptor Density(Pre-dose on Day 1)
- CD38 Receptor Occupancy(Pre-dose on Day 15)
- Number of Participants With Infusion Reactions (IRs)(From the time of the first treatment administration (Day 1) up to 30 days after the last treatment (maximum duration of exposure of 13.1 weeks for B-ALL cohort, 10.7 weeks for T-ALL cohort and 7.1 weeks for AML cohort))
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)(From the time of the first treatment administration (Day 1) up to 30 days after the last treatment (maximum duration of exposure of 13.1 weeks for B-ALL cohort, 10.7 weeks for T-ALL cohort and 7.1 weeks for AML cohort))
- B-ALL and T-ALL: Area Under the Concentration Time Curve (AUC) of Isatuximab(From Week 0 to Week 1, Week 0 to Week 5, and Week 0 to Week 10)
- B-ALL and T-ALL: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough)(Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 22, Cycle 1 Day 29, Cycle 2 Day 43, Cycle 2 Day 57)
- AML: Ceoi of Isatuximab(At end of infusion on Cycle 1 Days 1 and 15)
- Overall Survival (OS)(From first study treatment administration up to death due to any cause, a maximum of 45 months)
- B-ALL and T-ALL: Concentrations at the End of Infusion (Ceoi) of Isatuximab(At end of infusion on Cycle 1 Days 1 and 29)
- Number of Participants With Negative Minimal Residual Disease (MRD)(From screening until the study completion date, approximately 45 months)
- Overall Response Rate (ORR)(From enrollment until the primary analysis completion date of 12 Sep 2022; the median duration of exposure was approximately 7 weeks)
- Duration of Response (DoR)(From first documented response up to the date of first documented disease progression or death due to any cause, a maximum of 45 months)