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

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)

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 Overview

• Status: Completed
• Conditions: Peripheral T Cell Lymphoma; Transformed Mycosis Fungoides
• Intervention / Treatment: Drug: AFM13

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • Royal Adelaide Hospital
  • Bedford Park, Australia
    • Flinders Medical Centre
  • Clayton, Australia
    • Monash Health-Monash Medical Centre
  • Concord, Australia
    • Concord Repatriation General Hospital
  • Gosford, Australia
    • Gosford Hospital
  • Nedlands, Australia
    • Linear Clinical Research
• France
  • Bordeaux, France
    • Centre Hospitalier Universitaire (CHU) de Bordeaux
  • Brest, France
    • Centre Hospitalier Universitaire de Brest
  • La Roche Sur Yon, France
    • CHD Vendee
  • Rennes, France
    • Chu Pontchaillou
  • Villejuif, France
    • Institut Gustave Roussy
• Germany
  • Essen, Germany
    • Kliniken Essen Sued - Evangelisches Krankenhaus Essen-Werden gGmbH
  • Leipzig, Germany
    • University Hospital Leipzig
  • Mainz, Germany
    • Universitaetsmedizin Mainz
  • Muenchen, Germany
    • Rotkreuzklinikum Muenchen
• Italy
  • Bologna, Italy
    • Ist.Ematologia E Oncologia Medica L.E A.Seragnoli
  • Brescia, Italy
    • Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia
  • Meldola, Italy
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS
  • Milano, Italy
    • Azienda Ospedaliera Niguarda Ca' Granda
  • Ravenna, Italy
    • Azienda Unita Sanitaria Locale di Ravenna - Ospedale S. Maria delle Croci di Ravenna
• Korea, Republic of
  • Jeonju, Korea, Republic of
    • Chonbuk National University Hospital
  • Seongnam-si, Korea, Republic of
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Catholic University of Korea, Seoul St. Mary's Hospital
  • Ulsan, Korea, Republic of
    • Ulsan University Hospital
• Poland
  • Gdynia, Poland
    • Szpitale Pomorskie Sp. z o.o.. Szpital Morski im. PCK, Oddzial Hematologii i Transplantologii Szpiku
  • Kraków, Poland
    • PRATIA MCM Kraków
  • Warsaw, Poland
    • Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego
  • Warsaw, Poland
    • Instytut Hematologii i Transfuzjologii, Klinika Hematologii
  • Wrocław, Poland
    • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu. Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku
• Russian Federation
  • Petrozavodsk, Russian Federation
    • Republic Hospital n.a. V.A. Baranov
  • Saint Petersburg, Russian Federation
    • First State Saint-Petersburg Pavlov Medical University
  • Saratov, Russian Federation
    • Saratov State Medical University
  • St. Petersburg, Russian Federation
    • GUZ Leningrad Regional Clinical Hospital
  • St. Petersburg, Russian Federation
    • Russian Research Institute of Hematology and Transfusiology of the Federal Biomedical Agency
  • Tula, Russian Federation
    • Regional Clinical Hospital
• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain
    • Hospital del Mar
  • Barcelona, Spain
    • Hospital De La Santa Creu I Sant Pau
  • Barcelona, Spain
    • Duran I Reynals Hospital Catalan Institute Of Oncology
  • Barcelona, Spain
    • Institut Catala d'Oncologia Badalona, Hospital Germans Trias I Pujol
  • Girona, Spain
    • Institut Catala d' Oncologia Girona
  • Madrid, Spain
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre-Centro de Actividades Ambulatorias
  • Sevilla, Spain
    • Hospital Universitario Virgen del Rocio
  • Tarragona, Spain
    • Institut Catala d'Oncologia Tarragona
• Turkey
  • Ankara, Turkey
    • Ankara University Faculty of Medicine, Department of Internal Diseases, Hematology Division
  • Ankara, Turkey
    • Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim Arastirma Hastanesi Hematoloji Klinigi Ankara
  • Ankara, Turkey
    • Gazi University Faculty of Medicine, Department of Internal Diseases
  • Ankara, Turkey
    • Sağlık Bilimleri Üniversitesi Gülhane Eğitim ve Araştırm Hastanesi
  • Istanbul, Turkey
    • Istanbul Universitesi Istanbul Tip Fakultesi Ic Hastaliklari Anabilim Dali Hematoloji Bilim Dali Fatih
  • Samsun, Turkey
    • Ondokuz Mayis Universitesi Tip Fakultesi Saglik Uyg. ve Egitim Merkezi
  • Tekirdag, Turkey
    • Tekirdag Namik Kemal Universitesi Saglik Uygulama ve Arastirma Hastanesi
  • Trabzon, Turkey
    • KaradenizTeknik Universitesi Tip Fakultesi Farabi Hastanesi
  • İzmir, Turkey
    • Ege University Medical Faculty
  • İzmit, Turkey
    • Kocaeli University Faculty of Medicine, Department of Internal Diseases, Hematology Division
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham (O'Neal Comprehensive Cancer Center)
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Los Angeles, California, United States, 90404
      • University of California Los Angeles (UCLA) Health
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Clinic/Winship Cancer Institute
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation/Precision Cancer Therapies Program
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health | Rogel Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10019
      • Center for Lymphoid Malignancies
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of The University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Md Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Main 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; Subjects with Relapsed or Refractory CD30 positive Peripheral T-cell Lymphoma (PTCL).	Drug: AFM13; weekly intravenous infusions of 200mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 28 months).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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).	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).	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).	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).	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).	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.	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.	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.	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.	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.	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.	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.	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.	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.	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).	Pre-dose Day 1 on cycle 1 and end of treatment, up to approximately 46 months.

Collaborators and Investigators

• Sponsor: Affimed GmbH
• Investigators: Study Director: Karenza Alexis, MD, Affimed Inc.; Principal Investigator: Won Seog Kim, Dr, Samsung Medical Center; Principal Investigator: Steven Horwitz, MD, Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2019
• Primary Completion (Actual): May 11, 2022
• Study Completion (Actual): January 11, 2024

Study Registration Dates

• First Submitted: September 20, 2019
• First Submitted That Met QC Criteria: September 23, 2019
• First Posted (Actual): September 24, 2019

Study Record Updates

• Last Update Posted (Actual): November 5, 2024
• Last Update Submitted That Met QC Criteria: November 4, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Infections; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Bacterial Infections and Mycoses; Lymphoma, T-Cell, Cutaneous; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Mycoses; Mycosis Fungoides
• Other Study ID Numbers: AFM13-202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No