A Multi-Center, Open-Label, Phase 1/2 Clinical Trial to Evaluate the Safety and Anti-Tumor Activity of AB-101 Monotherapy and AB-101 With Immunotherapy in Patients With Relapsed/Refractory Non-Hodgkin Lymphoma of B-Cell Origin.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 22
- 主要终点
- Phase 1: Safety and tolerability of AB-101 as monotherapy, and in combination with rituximab (including the DLBCL specific cohort) and in combination with bendamustine and rituximab.
研究概览
简要总结
AB-101 is an off-the shelf, allogeneic cell product made of "natural killer" cells, also called NK cells. White blood cells are part of the immune system and NK cells are a type of white blood cell that are known to kill cancer cells.
This clinical trial will enroll patients with relapsed/refractory non-Hodgkin lymphoma of B-cell origin and is conducted in two phases. The primary objectives of Phase 1 are as follows: 1) to evaluate the safety of AB-101 given alone or in combination with rituximab (including the DLBCL specific cohort) or in combination with bendamustine and rituximab; 2) to evaluate the potential clinical activity of AB-101 when given in combination with rituximab or in combination with bendamustine and rituximab (combination cohorts only); and 3) to identify the recommended Phase 2 dose (RP2D). The primary objective of Phase 2 is to determine whether AB-101 in combination with rituximab or in combination with bendamustine and rituximab has anti-cancer activity in patients.
Patients will be assigned to receive either AB-101 alone as monotherapy, in combination with rituximab (including DLBCL specific cohort) or in combination with bendamustine and rituximab. All patients will receive at least 1 treatment cycle of AB-101, followed by scheduled assessments of overall health and tumor response. Patients receiving AB-101 in combination with rituximab may receive up to 3 additional cycles of treatment. Patients receiving AB-101 in combination with bendamustine and rituximab may receive up to 5 additional cycles of treatment. Patients enrolled into the DLBCL specific cohort receiving AB-101 in combination with rituximab may receive up to 3 cycles of 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
- •Confirmed diagnosis of aggressive NHL of B-cell origin. For enrollment into the DLBCL specific cohort: DLBCL, High-grade B-cell Lymphoma or PMBCL.
- •Patient must have progressed or demonstrated intolerance to at least two lines of FDA-approved therapies, one of which must have included anti-CD20 monoclonal antibody therapy. The following are permitted: Prior autologous hematopoietic stem cell transplantation, prior treatment with FDA-approved CAR-T therapy, and/or prior treatment with an investigational agent. Prior treatment(s) with an FDA-approved CAR-T cell therapy or other cell therapies is permitted as long the patients are not considered to be refractory to this previous cell therapy approach (defined as progression within 120 days from the infusion of the cell therapy approach).
- •Patient must have disease that allows for response assessment using the Lugano classification criteria.
- •Ability to understand and sign the ICF.
排除标准
- •Active CNS lymphoma or CNS involvement unless there is a history of at least 3 months of sustained remission of treated disease.
- •History of clinically significant structural cardiac disease.
- •Cardiac ejection fraction of < 45% on echocardiogram or MUGA scan at screening assessment.
- •Inadequate pulmonary function.
- •History of a solid organ allograft, or an inflammatory or autoimmune disease likely to be exacerbated by IL-
- •Ongoing uncontrolled systemic infections.
- •Positive HIV PCR test
- •Positive for Hepatitis B or Hepatitis C
- •Prior allogeneic stem cell transplant.
- •Females of childbearing potential must be willing and able to use appropriate contraception for duration of trial and for 6 months following final AB-101 dose. Males must be sterile or commit to using appropriate contraception until 90 days following the final dose of AB-
- •Individuals who are pregnant or lactating are ineligible.
- •Patients who received a previous genetically modified cell therapy product (e.g., CD19 CAR-T), and progressed within 120 days from the time of the cell therapy infusion
研究组 & 干预措施
Phase 1: Dose confirmation of AB-101 as mono, ritux combo (including DLBCL specific) & BR combo
Phase 1: Dose confirmation of AB-101 as monotherapy, in combination with rituximab (including the DLBCL specific cohort) and in combination with bendamustine and rituximab
干预措施: AB-101 (Drug)
Phase 2: AB-101 given with rituximab or with BR to patients with B-cell NHL at the R2PD
Phase 2: AB-101 given with rituximab or with bendamustine and rituximab to patients with B-cell NHL at the R2PD
干预措施: AB-101 (Drug)
Phase 1: Dose confirmation of AB-101 as mono, ritux combo (including DLBCL specific) & BR combo
Phase 1: Dose confirmation of AB-101 as monotherapy, in combination with rituximab (including the DLBCL specific cohort) and in combination with bendamustine and rituximab
干预措施: Rituximab (Drug)
Phase 1: Dose confirmation of AB-101 as mono, ritux combo (including DLBCL specific) & BR combo
Phase 1: Dose confirmation of AB-101 as monotherapy, in combination with rituximab (including the DLBCL specific cohort) and in combination with bendamustine and rituximab
干预措施: Interleukin-2 (Drug)
Phase 1: Dose confirmation of AB-101 as mono, ritux combo (including DLBCL specific) & BR combo
Phase 1: Dose confirmation of AB-101 as monotherapy, in combination with rituximab (including the DLBCL specific cohort) and in combination with bendamustine and rituximab
干预措施: Cyclophosphamide (Drug)
Phase 2: AB-101 given with rituximab or with BR to patients with B-cell NHL at the R2PD
Phase 2: AB-101 given with rituximab or with bendamustine and rituximab to patients with B-cell NHL at the R2PD
干预措施: Rituximab (Drug)
Phase 1: Dose confirmation of AB-101 as mono, ritux combo (including DLBCL specific) & BR combo
Phase 1: Dose confirmation of AB-101 as monotherapy, in combination with rituximab (including the DLBCL specific cohort) and in combination with bendamustine and rituximab
干预措施: Fludarabine (Drug)
Phase 1: Dose confirmation of AB-101 as mono, ritux combo (including DLBCL specific) & BR combo
Phase 1: Dose confirmation of AB-101 as monotherapy, in combination with rituximab (including the DLBCL specific cohort) and in combination with bendamustine and rituximab
干预措施: Bendamustine (Drug)
Phase 2: AB-101 given with rituximab or with BR to patients with B-cell NHL at the R2PD
Phase 2: AB-101 given with rituximab or with bendamustine and rituximab to patients with B-cell NHL at the R2PD
干预措施: Cyclophosphamide (Drug)
Phase 2: AB-101 given with rituximab or with BR to patients with B-cell NHL at the R2PD
Phase 2: AB-101 given with rituximab or with bendamustine and rituximab to patients with B-cell NHL at the R2PD
干预措施: Interleukin-2 (Drug)
Phase 2: AB-101 given with rituximab or with BR to patients with B-cell NHL at the R2PD
Phase 2: AB-101 given with rituximab or with bendamustine and rituximab to patients with B-cell NHL at the R2PD
干预措施: Bendamustine (Drug)
Phase 2: AB-101 given with rituximab or with BR to patients with B-cell NHL at the R2PD
Phase 2: AB-101 given with rituximab or with bendamustine and rituximab to patients with B-cell NHL at the R2PD
干预措施: Fludarabine (Drug)
结局指标
主要结局
Phase 1: Safety and tolerability of AB-101 as monotherapy, and in combination with rituximab (including the DLBCL specific cohort) and in combination with bendamustine and rituximab.
时间窗: From the ICF signature through 13 weeks after last study drug dose.
Based on incidence, severity, and dose relationship of AEs and serious AEs (SAEs)
Phase 1, combination therapy: AB-101 clinical activity, determined by ORR
时间窗: From baseline disease assessment through end of study participation.
Objective response rate (ORR) is defined as the proportion of patients with a documented complete response or partial response (CR + PR) in the absence of earlier disease progression.
Phase 1, combination therapy: Identify the recommended Phase 2 dose (R2PD) for AB-101.
时间窗: From ICF signature through 13 weeks after last study drug dose.
R2PD will be determined based on safety and tolerability of AB-101 in combination with rituximab or in combination with bendamustine and rituximab.
Phase 2: Determine the efficacy profile of AB-101 in combination with rituximab or in combination with bendamustine and rituximab when administered to patients with R/R NHL of B-cell origin.
时间窗: From baseline disease assessment through end of study participation.
The efficacy profile will be determined by the ORR.
次要结局
未报告次要终点