A Phase I/II Open Label Study To Evaluate The Safety, Pharmacokinetics And Pharmacodynamics Of ALXN6000 In Patients With Relapsing Or Refractory B-Cell Chronic Lymphocytic Leukemia Or Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 26
- 主要终点
- Number Of Participants With Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
The purpose of this study was to determine the safety and maximum tolerated dose (MTD) of ALXN6000 (samalizumab) in treating relapsing or refractory B-cell chronic lymphocytic leukemia (B-CLL) or multiple myeloma (MM) and to study how samalizumab may help the immune system fight tumors that express CD200.
详细描述
This was an open-label multicenter study for participants with relapsing or refractory B-CLL or MM. The study was planned to be conducted in 2 parts: Part A and Part B. Both parts were to evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy (to the extent possible) of samalizumab in the target participant population. Part A was designed as the open-label, intravenous (IV) single dose-escalation portion of the study to determine the MTD and to assess the overall safety of different dose levels of up to 4 IV doses of samalizumab in participants with either refractory or relapsing B-CLL or MM. Initially, at least 3 participants would be enrolled into a cohort until a dose-limiting toxicity (DLT) was reached. If any 1 of the initial 3 participants in the cohort experienced a DLT, the cohort would be expanded to at least 6 participants.
After determination of the MTD in Part A, the Sponsor was to review the safety, PK, and relevant PD data to determine the dosing administration schedule for Part B. However, no participants were enrolled for Part B, as the study was terminated by the Sponsor for administrative reasons.
Participant enrollment in Cohort 7 (600 milligrams per square meter [mg/m^2] dose level), Part A, was halted after enrollment of the first participant. The study was terminated by the Sponsor for administrative reasons and not due to any safety concerns. Participants who were on study at the time of study termination were allowed to continue until the expiry date of the drug lot being used and then were followed for 30 (±1) days per protocol. The study was terminated by the Sponsor at that time. Part B of the study was not conducted.
研究设计
- 研究类型
- Interventional
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Relapsing or Refractory B-CLL or MM
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- •Anticipated survival of greater than 6 months
- •Female participants of childbearing potential must agree to use 2 forms of contraception
- •Participants must have a standard indication for treatment of their malignancy
- •Is willing and able to give written informed consent prior to any procedure not considered standard of care
排除标准
- •Absolute neutrophil count (ANC) < 1000 x 10^9/liter (L)
- •Platelet count < 50,000 x 10^9/L
- •Pregnant or lactating women
- •Prior history of autoimmune hemolysis requiring therapy
- •Prior history of immune thrombocytopenia
- •Active autoimmune disease requiring immunosuppressive therapy
- •Positive Coombs' Test (neither direct or indirect)
- •Ongoing corticosteroid treatment equivalent to the mineralocorticoid potency of 10 milligrams (mg) /day of prednisone, or greater, for any condition
- •Prior stem cell transplantation within 4 weeks prior to enrollment
- •Prior chemotherapy for the applicable malignancy within 30 days of enrollment
- •Neurosurgery or cranial radiation therapy within 1 year of enrollment
- •Clinically significant renal, hepatic, or cardiopulmonary disease
研究组 & 干预措施
Samalizumab
All doses of samalizumab were individualized based on the participant's body surface area in mg/m^2 based on screening height and weight. Participants were assigned to a dose cohort, ranging from 50 to 600 mg/m^2, and received a single IV dose of samalizumab. Participants who tolerated the drug and demonstrated at least stable disease received up to 3 additional cycles of samalizumab at the same dose originally received at a minimum of 28-day intervals and beginning no sooner than 6 weeks after the initial dose. If no participants enrolled into a cohort experienced a DLT, escalation to the next dose level occurred with a new cohort. If any 1 of the initial 3 participants in the cohort experienced a DLT, the cohort was expanded to at least 6 participants. Then, if less than one third of participants within the cohort experienced a DLT, escalation to the next dose level occurred with a new cohort. Dose cohorts were enrolled sequentially.
干预措施: Samalizumab (Drug)
结局指标
主要结局
Number Of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: From first dose through 10 weeks after the last dose
A TEAE was defined as any event not present prior to exposure to samalizumab or any event already present that worsened in either intensity or frequency following exposure to samalizumab. A treatment-emergent serious adverse event was defined as any event that resulted in death, was immediately life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Maximum Tolerated Dose (MTD) Of Samalizumab
时间窗: From first dose through 10 weeks after the last dose
The MTD was to be defined as the dose level at which less than one-third of participants experienced a dose-limiting toxicity (DLT) during the first 28 days of treatment and immediately below the dose at which at least one-third of participants experienced a DLT. A DLT was defined as any Grade 3 or greater toxicity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 not related to the disease under study or its sequelae that occurred in the first 28 days after dosing in Cycle 1. The NCI CTCAE grading system for the organ of involvement was used to classify severity of adverse autoimmune reactions.
次要结局
- Density Of B-CLL Cells Bound At Baseline (Predose) And Day 1 (Postdose)(Baseline (Predose) and Day 1 (Postdose))
- Percent Of Bound Samalizumab On B-Cell Chronic Lymphocytic Leukemia (B-CLL) Cells In Participants With B-CLL At Baseline (Predose) And Day 1 (Postdose)(Baseline (Predose) and Day 1 (Postdose))
- Clinical Response Of Participants With B-CLL Following Samalizumab Dosing Using Modified NCI Working Group Response Criteria For ORR Rate(From first dose through 10 weeks after the last dose)
- Clinical Response Of Participants With Multiple Myeloma (MM) Following Dosing With Samalizumab(From first dose through 10 weeks after the last dose)