Phase II Study to Assess AFM13 in Patients With R/R CD30-positive T-cell Lymphoma or Transformed Mycosis Fungoides

Phase 2

Completed

Conditions: Peripheral T Cell Lymphoma
Transformed Mycosis Fungoides

Interventions: Drug: AFM13

Registration Number: NCT04101331

Lead Sponsor: Affimed GmbH

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 108

Inclusion Criteria

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

Main

Exclusion Criteria

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cohort A	AFM13	Subjects with Relapsed or Refractory CD30 positive Peripheral T-cell Lymphoma (PTCL).

Primary Outcome Measures

Name	Time	Method
Overall 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 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).

Secondary Outcome Measures

Name	Time	Method
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).	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).
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).	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.
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.	Maximum measured concentration (Cmax) of the AFM13 in serum. Geometric coefficient of variation is given in percentages.
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.	The terminal half-life (t1/2) of the AFM13. Geometric coefficient of variation is given in percentages.
European Quality of Life 5-dimensional Pain/Discomfort Score (EQ-5D)	At baseline and final study visit, up to 199 weeks.	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.
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 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).
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).	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).
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).	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).
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.	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.
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).	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.
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.	Number of subjects who had treatment (AFM13) related Adverse Events.
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.	Volume of distribution at steady state (Vss) of the AFM13. Geometric coefficient of variation is given in percentages.
European Quality of Life 5-dimensional Visual Analogue Scale Scores (EQ-5D)	From baseline until final study visit, up to 199 weeks.	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.
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.	Number of subjects who had treatment (AFM13) and developed anti-drug antibodies (ADA).
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 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).
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 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).

Trial Locations

Locations (69): University of Alabama at Birmingham (O'Neal Comprehensive Cancer Center)
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Birmingham, Alabama, United States
City of Hope Comprehensive Cancer Center
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Duarte, California, United States
University of California Los Angeles (UCLA) Health
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Los Angeles, California, United States
Emory University Clinic/Winship Cancer Institute
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Atlanta, Georgia, United States
Ochsner Clinic Foundation/Precision Cancer Therapies Program
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New Orleans, Louisiana, United States
University of Michigan Health | Rogel Cancer Center
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Ann Arbor, Michigan, United States
Mayo Clinic
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Rochester, Minnesota, United States
Center for Lymphoid Malignancies
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New York, New York, United States
Memorial Sloan Kettering Cancer Center
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New York, New York, United States
Abramson Cancer Center of the University of Pennsylvania
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Philadelphia, Pennsylvania, United States
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University of Alabama at Birmingham (O'Neal Comprehensive Cancer Center)
🇺🇸Birmingham, Alabama, United States