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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
108
weekly intravenous infusions of 200mg
University of Alabama at Birmingham (O'Neal Comprehensive Cancer Center)
Birmingham, Alabama, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
University of California Los Angeles (UCLA) Health
Los Angeles, California, United States
Emory University Clinic/Winship Cancer Institute
Atlanta, Georgia, United States
Ochsner Clinic Foundation/Precision Cancer Therapies Program
New Orleans, Louisiana, United States
Overall Response Rate Assessed by Independent Review Committee Based on PET-CT
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).
Time frame: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 28 months).
Overall Response Rate Assessed by Investigator Based on PET-CT
Overall response by Positron Emission Tomography-Computed Tomography (PET-CT) as defined by achieving complete response and/or partial response assessed by the investigator utilizing the modified Lugano Classification Revised Staging System for malignant lymphoma (Cheson, 2014).
Time frame: 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
Overall response by Computed Tomography (CT) as defined by achieving complete response and/or partial response assessed by the investigator utilizing the modified Lugano Classification Revised Staging System for malignant lymphoma (Cheson, 2014).
Time frame: 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 and Partial Response Rate Assessed by Independent Review Committee Based on PET-CT
Complete response and/or partial response by Positron Emission Tomography-Computed Tomography (PET-CT) assessed by an Independent Review Committee (IRC) utilizing the modified Lugano Classification Revised Staging System for malignant lymphoma (Cheson, 2014).
Time frame: 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
Overall response by Computed Tomography (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).
Time frame: 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
Duration of response (DOR) defined as the period from first Partial Response (PR) and Complete Response (CR) assessment till first assessment of progressive disease or death. Response assessed by Positron Emission Tomography-Computed Tomography (PET-CT) by Independent Review Committee (IRC).
Time frame: 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 CT
Duration of response (DOR) defined as the period from first Partial Response (PR) and Complete Response (CR) assessment till first assessment of progressive disease or death. Response assessed by Computed Tomography (CT) by Independent Review Committee (IRC).
Time frame: 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
Duration of response (DOR) defined as the period from first Partial Response (PR) and Complete Response (CR) assessment till first assessment of progressive disease or death. Response assessed by Positron Emission Tomography-Computed Tomography (PET-CT) by the investigator.
Time frame: 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
Duration of response (DOR) defined as the period from first Partial Response (PR) and Complete Response (CR) assessment till first assessment of progressive disease or death. Response assessed by Computed Tomography (CT) by the investigator.
Time frame: 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
Number of subjects who had treatment (AFM13) related Adverse Events.
Time frame: From the date of first treatment until the date of the last treatment + 37 days, up to 199 weeks.
Maximum Measured Concentration (Cmax) of AFM13
Maximum measured concentration (Cmax) of the AFM13 in serum. Geometric coefficient of variation is given in percentages.
Time frame: 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.
Area Under the Concentration-Time Curve of AFM13 From 0 to Infinity (AUC 0-∞)
Area under concentration (AUC) versus time curve of the AFM13 in serum over time interval from 0 extrapolated to infinity. Geometric coefficient of variation is given in percentages.
Time frame: 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.
Volume of Distribution at Steady State (Vss) of AFM13
Volume of distribution at steady state (Vss) of the AFM13. Geometric coefficient of variation is given in percentages.
Time frame: 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.
The Terminal Half-life (t1/2) of AFM13
The terminal half-life (t1/2) of the AFM13. Geometric coefficient of variation is given in percentages.
Time frame: 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)
Quality of Life (QoL) as measured by the European QoL 5-dimensional questionnaire (EQ-5D) for Cohorts A. The EQ-5D comprises asks for the current health state in the five dimensions: mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Pain/discomfort scores assessed based on questionnaire. The categories of the response offer three levels pain/discomfort score: "no pain or discomfort" (score of 1), "moderate pain or discomfort" (score of 2), and "extreme pain and discomfort" (score of 3). Scores are presented from baseline to each visit for Cohort A.
Time frame: At baseline and final study visit, up to 199 weeks.
European Quality of Life 5-dimensional Visual Analogue Scale Scores (EQ-5D)
Quality of Life (QoL) as measured by the European Quality of Life 5-dimensional questionnaire (EQ-5D) for Cohorts A. Visual Analogue Scale scores assessed based on drawn scale from 0(worst imaginable state) to 100(best imaginable state). Subjects chose their health state on scale based on their situation by themselves. A negative outcome indicates a decrease in score compared to the baseline value.
Time frame: From baseline until final study visit, up to 199 weeks.
Number of Subjects Who Developed Anti-drug Antibodies (ADA) During Treatment
Number of subjects who had treatment (AFM13) and developed anti-drug antibodies (ADA).
Time frame: Pre-dose Day 1 on cycle 1 and end of treatment, up to approximately 46 months.
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University of Michigan Health | Rogel Cancer Center
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