Open Label 1b/2a Trial of a Combination of IPH2201 and Ibrutinib in Patients With Relapsed, Refractory or Previously Untreated Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Rate of Complete Response (CR)
研究概览
简要总结
Combination study of monalizumab (IPH2201) with Ibrutinib in relapsed, refractory or previously untreated Chronic Lymphocytic Leukemia (CLL) patients in 2 parts :
- phase 1 : a 3+3 design to assess the Maximum Tolerated Dose (MTD)
- phase 2: to evaluate the anti-leukemic activity of the combination
详细描述
This trial was designated to test the hypothesis that the combination of ibrutinib and IPH2201 will result in a substantial complete response (CR) rate, especially CR without minimal residual disease (MRD), as this has been shown to be associated with long-term clinical benefit.
Up to 45 patients were planned to be enrolled. During the phase 1 part a 3+3 dose escalation design was employed. Four doses were planned to be assessed if the Maximum Tolerated Dose (MTD) was not previously reached: 1, 2, 4 and 10 mg/kg.
During phase 2 part, patients received monalizumab in combination with ibrutinib; monalizumab was given at the dose recommended upon completion of the phase I portion.
The primary objective of the phase 1 was to assess the safety of monalizumab given intravenously as a single agent and in combination with ibrutinib in patients with relapsed, refractory or previously untreated Chronic Lymphocytic Leukemia.
The primary objective of the phase 2 was to evaluate the anti-leukemic activity of the combination of monalizumab and ibrutinib in patients with relapsed, refractory or previously untreated Chronic Lymphocytic Leukemia.
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
- •Confirmed diagnosis of Chronic Lymphocytic Leukemia (CLL)
- •Relapsed, refractory or previously untreated CLL
- •CLL requiring treatment; patients must be eligible for ibrutinib therapy
- •Age > = 18 years
- •Eastern Cooperative Oncology Group performance status of 0-2
- •Life expectancy > = 3 months
- •Adequate liver and renal function
- •Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of the study participation
- •Ability to understand a written informed and consent document
- •Signed informed consent prior to any protocol-specific procedures
排除标准
- •Patients who have previously received ibrutinib or another inhibitor of Bruton's tyrosine kinase (BTK)
- •History of allergic reactions attributed to compounds or similar chemical or biological composition to ibrutinib
- •Central nervous system involvement of the CLL
- •Abnormal hematological function which is not due to bone marrow failure related to the CLL
- •Patients requiring a treatment by oral vitamin K antagonists
- •Serious uncontrolled medical disorder
- •Medical condition or organ system dysfunction which, in the investigator opinion, could interfere with absorption or metabolism of ibrutinib
- •Moderate or severe hepatic impairment
- •Active auto-immune disease
- •Abnormal cardiac status
- •Pregnant women are excluded from study
- •Current active infectious disease
- •History of another malignancy within 3 years
- •History of allogeneic stem cell or solid organ transplantation
研究组 & 干预措施
Phase 1 Level 1 - 1 mg/kg
In phase 1, Monalizumab given at the first dose level of 1 mg/kg.
干预措施: monalizumab (Drug)
Phase 1 Level 2 - 2 mg/kg
In phase 1, Monalizumab given at the second dose level of 2 mg/kg.
干预措施: monalizumab (Drug)
Phase 1 Level 3 - 4 mg/kg
In phase 1, Monalizumab given at the third dose level of 4 mg/kg.
干预措施: monalizumab (Drug)
Phase 2 RP2D - 2 mg/kg
In phase 2, Monalizumab given at the Recommended Phase 2 Dose (RP2D) of 2 mg/kg, selected by a safety committee.
干预措施: monalizumab (Drug)
结局指标
主要结局
Rate of Complete Response (CR)
时间窗: CR assessed 52 weeks after the beginning of combination treatment
The rate of complete response (CR) was evaluated using the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) grading scale and confirmed by a bone marrow biopsy. Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL), Complete Response (CR) is defined as lymphocytes \<4x109/l, absence of lymphadenopathy, hepatomegaly and splenomegaly at CT scan, no constitutional symptoms, no cytopenia, normocellular bone marrow. Partial Response (PR) is a reduction \> 50% in lymphocytes, lymphadenopathy, spleen or liver, no cytopenia. PD if appearance of any new lesion, or increase in lymphocytes \> 50%, or occurrence of cytopenia attributable to CLL.
Number of Dose Limiting Toxicities
时间窗: 8 weeks
Number of dose-limiting toxicities, measured during the phase 1, dose escalation, part of the study.
次要结局
- Best Overall Response / Remission Rates(From beginning of study drug treatment to the end of study (up to 24 months))
- Progression Free Survival(Up to 24 months)
- Duration of Remission(Up to 24 months)
- Overall Survival(Up to 24 months.)