A Phase I/IIa Multicenter Study Evaluating the Safety and Efficacy of CAR20(NAP)-T in Patients With Relapsed/Refractory B Cell Lymphoma (CARMA-01 Study)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Incidence of dose limiting toxicity
研究概览
简要总结
The purpose is to study the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of CAR20(NAP)-T for patients with B-cell malignancies.
详细描述
A cancer patient's T cells can be isolated and engineered to express a chimeric antigen receptor (CAR), which re-directs the T cells to recognize and kill tumor cells expressing that particular antigen. CD19-targeted CAR-T cell therapy has shown good effects for B cell malignancies, even cure, in otherwise therapy refractory patients.
Antigen escape, i.e., the downregulation of the antigen targeted by the CAR due to the selective pressure caused by the CAR-T cell therapy is a challenge. For patients treated with CD19 CAR-T cell therapy, about 30% of the patients are resistant to treatment and about 20% of patients relapse after an initial response.
CAR20(NAP)-T cells target CD20 and upon target recognition secrete a bacterial-derived pluripotent immune-stimulating factor named NAP (Helicobacter pylori Neutrophil-activating protein). Secretion of NAP in the tumor microenvironment can induce an endogenous bystander immune response, that counteracts antigen escape and thereby improves the therapeutic outcome.
CAR20(NAP)-T is an investigational agent not yet approved by authorities.
Design:
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent.
- •Relapsed or refractory CD20+ diffuse large B-cell lymphoma, mantle cell lymphoma or indolent lymphoma.
- •The patient should have been treated with at least two lines of therapy and have no curative treatment option, specifically
- •Relapsed or refractory CD20+ B-cell lymphoma that are not eligible to receive clinically approved CD19-directed CAR T cell treatment.
- •Relapsed or refractory CD20+ B-cell lymphoma who are CD19 negative.
- •Relapsed or refractory B-cell lymphoma who relapse after CD19 CAR T cell treatment.
- •In phase I age >18 years, in phase II all ages
- •Measurable disease per Lugano classification.
- •Performance status ECOG 0-
- •Adequate bone marrow function as evidenced by:
- •Absolute neutrophil count (ANC) ≥ 1x10^9/l/L
- •Platelet ≥ 50x 10^9/l
- •Absolute lymphocyte count ≥ 0,1x10^9/L
- •Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by:
- •Creatinine clearance (Cockcroft Gault) ≥ 30 mL/min
- •Serum Alanine aminotransferase/Aspartate aminotransferase (ALT/AST) ≤ 2.5 Upper limit of normal (ULN) and S-Bilirubin <1.5x UNL
- •Cardiac ejection fraction ≥ 40%
- •Functional venous for administration of IMP.
- •Fertile individuals must consent to use contraceptives during participation in the trial.
排除标准
- •Other CD20-positive lymphomas i.e Burkitt lymphoma, primary CNS lymphoma, plasmablastic lymphoma or CLL transformed to DLBCL/HGBL (Richter transformation)
- •Any significant medical or psychiatric illness that would prevent the subject from giving informed consent or from following the study procedures.
- •Known human immunodeficiency virus (HIV) infection.
- •Impending organ-compromising disease.
- •Rapidly progressing disease
- •Active and/or severe infection (e.g., tuberculosis, sepsis and opportunistic infections, active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
- •Other serious underlying medical conditions, which, in the Investigator's judgment, could impair the ability of the subject to perform the treatment.
- •Treatment with an investigational product within 30 days prior to enrolment
- •Potential sign of hypersensitivity reaction to tocilizumab or any of the agents used in this study
- •Systemic corticosteroid treatment (>10mg/day) <5 days prior to IMP treatment or <7 days prior leukapheresis.
- •Pregnancy
研究组 & 干预措施
Treatment
CAR20(NAP)-T treatment
干预措施: CAR20(NAP)-T (Biological)
Treatment
CAR20(NAP)-T treatment
干预措施: Cyclophosphamide (Drug)
Treatment
CAR20(NAP)-T treatment
干预措施: Fludarabine (Drug)
结局指标
主要结局
Incidence of dose limiting toxicity
时间窗: First infusion up to 30 days
The incidence of dose limiting toxicity (DLT). Number of Participants Experiencing Adverse Events (AEs) Defined as Dose Limiting Toxicities (DLTs)
Adverse events
时间窗: 24 months
The nature, frequency, severity, and tolerability of adverse events (AEs) including clinically significant laboratory data, and their relation to dosage.
Pharmacodynamic (PD) and pharmacokinetic (PK)
时间窗: Either 24 month or 15 years during long-term follow up if clinically indicated
PD is assessed by determine circulating B cell level; PK is assessed by determine circulating CAR20(NAP)-T cells.
次要结局
- Progression free survival [PFS](24 months)
- Objective response rate [ORR](24 months)
- Best Objective Response(24 months)
- Duration of Response (DOR)(24 months)
- Overall Survival (OS)(either 24 months or 15 years during long-term follow up if clinically indicated)