A Phase I/II Multicenter Study Evaluating the Safety and Efficacy of Allogeneic GDA-201 Natural Killer Cells in Patients With Relapsed/Refractory B Cell Non-Hodgkin Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 13
- 试验地点
- 6
- 主要终点
- Phase I: Safety as Determined by Dose Limiting Toxicities (DLTs)
研究概览
简要总结
This is an open-label, non-randomized, interventional, single group assignment study of GDA-201, an allogeneic cryopreserved Natural Killer (NK) cell therapy derived from donor peripheral blood, in combination with rituximab, monoclonal anti-CD20 antibody, for patients with relapsed or refractory B Cell non-Hodgkin lymphoma (NHL).
详细描述
The study is divided into a phase I dose escalation phase and a phase II expansion phase.
Patients with relapsed or refractory follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL)/high grade B-cell lymphoma (HGBCL) will receive GDA-201 followed by a short course of low-dose interleukin-2 (IL-2). Rituximab will be administered prior to and after GDA-201 infusion.
Phase I: Dose escalation phase The objective of Phase I is to evaluate the safety of GDA-201 in patients with FL, DLBCL/ HGBCL, marginal zone lymphoma or mantle cell lymphoma. The maximal tolerated dose (MTD) and recommended Phase II Dose (RP2D) will be determined based on dose limiting toxicities (DLT).
Phase II expansion phase The objective of the Phase II expansion cohort is to evaluate the safety and efficacy of GDA-201 in two patient cohorts, FL and DLBCL/HGBCL.
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
- •Patients must have relapsed/refractory FL or HGBCL/DLBCL that has failed conventional therapy defined as follows:
- •Received at least 2 prior lines of therapy
- •Transplant ineligible patients allowed assuming they meet criterion a.
- •Patients who received prior chimeric antigen receptor modified T-cells (CAR-T) cell therapy or are considered ineligible for CAR-T therapy per the investigator's discretion
- •FL transformed to HGBCL: Must have received at least 1 line of therapy after transformation to DLBCL/HGBCL
- •Patients must be at least 18 years of age
- •Patients must have adequate hematologic, hepatic, renal, cardiac and pulmonary function prior to any study treatment.
排除标准
- •Central Nervous System (CNS) lymphoma
- •Time between previous treatment and first dose of study treatment (rituximab):
- •Allogeneic hematopoietic stem cell transplantation (HSCT) < 6 months prior to study treatment
- •Autologous HSCT < 3 months prior to study treatment
- •CAR-T < 2 months prior to study treatment
研究组 & 干预措施
GDA-201 Cohort 1 (Phase I)
Dose escalation with up to 4 dose levels to reach MTD and determine recommended Phase II dose (RP2D).
干预措施: GDA-201 (Drug)
GDA-201 Cohort 2 (Phase II)
RP2D will be administered to all patients.
干预措施: GDA-201 (Drug)
结局指标
主要结局
Phase I: Safety as Determined by Dose Limiting Toxicities (DLTs)
时间窗: Day 28
DLTs defined as one of the following within the first 28 days of the first dose of GDA-201 by the NCI-CTCAE v 5.0. acute graft-versus-host disease (aGvHD) will be assessed according to the Consensus Conference on aGvHD grading: Steroid refractory Grade II aGvHD, defined as GvHD that does not respond to at least 1 mg/kg/day or equivalent of prednisone within 7 days of initiating therapy Grade III or IV aGvHD Grade 4 infusion reaction Grade 4 or 5 related adverse event (AE) Grade 3 or above cardiac, central nervous system or pulmonary adverse event. Any Grade 3 or above non-hematologic adverse event that does not resolve to Grade 2 or below within 72 hours, except for renal or hepatic adverse events which may take up to 7 days to resolve Treatment emergent ≥Grade 3 autoimmune disorder Grade 3 or above allergic reaction that does not recover to Grade II or below within 24 hours Grade 4 cytopenia lasting beyond Day 42 (the 28-day DLT observation period will be extend
Phase II: Overall Response Rate
时间窗: up to 1 year
Patients will be assessed after the infusion of GDA-201 for level of response.
次要结局
未报告次要终点