A Phase II Open-label Multicenter Study to Assess the Efficacy and Safety of AFM13 in Patients With Relapsed or Refractory CD30-positive Peripheral T-cell Lymphoma or Transformed Mycosis Fungoides (REDIRECT)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Affimed GmbH
- 入组人数
- 108
- 试验地点
- 69
- 主要终点
- Overall Response Rate Assessed by Independent Review Committee Based on PET-CT
研究概览
简要总结
This is a phase II study to evaluate the antitumor activity and safety of AFM13 given as monotherapy in patients with CD30-positive T-cell lymphoma. The investigational medicinal product AFM13 is a tetravalent bispecific chimeric (anti-human CD30 x anti-human CD16A) recombinant antibody construct which is being developed to treat CD30-positive malignancies.
Patients who suffer from peripheral T-cell lymphoma or transformed mycosis fungoides, whose tumor expresses the surface marker CD30, and who have relapsed after an earlier treatment or have refractory disease will be enrolled into this study if all of the study entry criteria are fulfilled. Dependent on their disease type and the magnitude of CD30 expression, study participants will be assigned to one of 3 study cohorts, each cohort receiving the same treatment of weekly AFM13 infusions (a 200mg dose per infusion).
The main goal of the study is to assess the efficacy of AFM13 treatment as judged by the rate of overall responses. Further goals are to assess the safety of AFM13 treatment, the immunogenicity of AFM13 (as measured by the potential formation of anti-AFM13 antibodies) and the concentration of AFM13 in the blood.
Approx. 1 month after the last dose of AFM13 there will be a final study visit to assess the patients' health status after therapy, followed by quarterly phone contacts to check on their overall health status and long-term survival.
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
- 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
- •Histologically confirmed CD30-positive PTCL (most subtypes allowed) or TMF per the revised World Health Organization 2016 classification (Swerdlow, 2016) by central assessment.
- •Cohorts A and B (PTCL cohorts): measurable by the modified Lugano Classification (Cheson, 2014); measurable disease of ≥1.5 cm diameter by computed tomography (CT), assessed locally for eligibility. Note: fluorodeoxyglucose (FDG) avid disease by positron emission tomography (PET) recommended, if possible.
- •Cohort C (TMF cohort): measurable by the Olsen Criteria (Olsen, 2011) including at least 1 cutaneous lymphoma lesion ≥2 cm in diameter, assessed locally for eligibility.
- •Patients must have relapsed or refractory disease AND the following:
- •Cohorts A and B (PTCL): patients must have received at least 1 prior line of systemic therapy. For patients with systemic ALCL, patients must have failed or be intolerant to brentuximab vedotin [BV]; Adcetris®
- •Cohort C (TMF): patients must have received at least 1 prior line of systemic therapy; and have exhausted systemic therapies with regular approval for their disease
排除标准
- •Patients with the following subtypes of lymphoma: T-cell prolymphocytic leukemia; T-cell large granular lymphocytic leukemia; Chronic lymphoproliferative disorder of NK cells; Aggressive NK-cell leukemia; Extranodal NK-/T-cell lymphoma; Indolent T-cell lymphoproliferative disorder of the GI tract:
- •Has had an allogenic tissue hematopoietic cell/solid organ transplant within the last 3 years. Note: Patients who have had a transplant >3 years ago are eligible as long as there are no signs/symptoms of graft versus host disease (GvHD).
- •Requirement for systemic immunosuppressive therapy, e.g. GvHD therapy, <12 weeks prior to the first dose of study drug.
- •Prior treatment with AFM13
研究组 & 干预措施
Cohort A
Subjects with Relapsed or Refractory CD30 positive Peripheral T-cell Lymphoma (PTCL).
干预措施: AFM13 (Drug)
结局指标
主要结局
Overall Response Rate Assessed by Independent Review Committee Based on PET-CT
时间窗: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 28 months).
Overall response by Positron Emission Tomography-Computed Tomography (PET-CT) as defined by achieving complete response and/or partial response assessed by an Independent Review Committee (IRC) utilizing the modified Lugano Classification Revised Staging System for malignant lymphoma (Cheson, 2014).
次要结局
- Complete Response Rate and Partial Response Rate Assessed by Independent Review Committee Based on PET-CT(Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 46 months).)
- Complete Response Rate, Partial Response Rate and Overall Response Rate Assessed by Independent Review Committee Based on CT(Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 46 months).)
- Duration of Overall Response Assessed by Investigator Based on PET-CT(Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 46 months).)
- Maximum Measured Concentration (Cmax) of AFM13(Predose and 1 hour after start of infusion, end of injection (EOI) and 1 hour, 2 hours, 3 hours, 24 hours and 48 hours after EOI on Cycle 1 Day 1 and Day 29.)
- The Terminal Half-life (t1/2) of AFM13(Predose and 1 hour after start of infusion, end of injection (EOI) and 1 hour, 2 hours, 3 hours, 24 hours and 48 hours after EOI on Cycle 1 Day 1 and Day 29.)
- European Quality of Life 5-dimensional Pain/Discomfort Score (EQ-5D)(At baseline and final study visit, up to 199 weeks.)
- Overall Response Rate Assessed by Investigator Based on PET-CT(Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 46 months).)
- Overall Response Rate Assessed by Investigator Based on CT(Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 46 months).)
- Duration of Overall Response Assessed by Independent Review Committee Based on PET-CT(Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 46 months).)
- Area Under the Concentration-Time Curve of AFM13 From 0 to Infinity (AUC 0-∞)(Predose and 1 hour after start of infusion, end of injection (EOI) and 1 hour, 2 hours, 3 hours, 24 hours and 48 hours after EOI on Cycle 1 Day 1 and Day 29.)
- Duration of Overall Response Assessed by Independent Review Committee Based on CT(Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 46 months).)
- Duration of Overall Response Assessed by Investigator Based on CT(Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 46 months).)
- Number of Subjects With Treatment Related Adverse Event(From the date of first treatment until the date of the last treatment + 37 days, up to 199 weeks.)
- Volume of Distribution at Steady State (Vss) of AFM13(Predose and 1 hour after start of infusion, end of injection (EOI) and 1 hour, 2 hours, 3 hours, 24 hours and 48 hours after EOI on Cycle 1 Day 29.)
- European Quality of Life 5-dimensional Visual Analogue Scale Scores (EQ-5D)(From baseline until final study visit, up to 199 weeks.)
- Number of Subjects Who Developed Anti-drug Antibodies (ADA) During Treatment(Pre-dose Day 1 on cycle 1 and end of treatment, up to approximately 46 months.)