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

Peripheral T Cell Lymphoma Clinical Trial

— REDIRECT  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04101331
• Other study ID #: AFM13-202
• Status: Completed
• Phase: Phase 2
• Start date: November 13, 2019
• Est. completion date: January 11, 2024

Study information

• Verified date: August 2023
• Source: Affimed GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: January 11, 2024
• Est. primary completion date: May 11, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Mycoses
• Mycosis Fungoides
• Peripheral T Cell Lymphoma
• Transformed Mycosis Fungoides

Intervention

Drug:
• AFM13
weekly intravenous infusions of 200mg

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Affimed GmbH

Countries where clinical trial is conducted

United States,  Australia,  France,  Germany,  Italy,  Korea, Republic of,  Poland,  Russian Federation,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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 28 months).
Secondary	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 28 months).
Secondary	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 28 months).
Secondary	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 28 months).
Secondary	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 26 months).
Secondary	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 26 months).
Secondary	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 26 months).
Secondary	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 26 months).
Secondary	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 138 weeks.
Secondary	Maximum Measured Concentration (Cmax) of AFM13	Maximum measured concentration (Cmax) of the AFM13 in plasma.	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.
Secondary	Area Under the Concentration-Time Curve of AFM13 From 0 to Infinity (AUC 0-8)	Area under concentration (AUC) versus time curve of the AFM13 in plasma over time interval from 0 extrapolated to infinity.	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.
Secondary	Volume of Distribution at Steady State (Vss) of AFM13	Volume of distribution at steady state (Vss) of the 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.
Secondary	The Terminal Half-life (t1/2) of AFM13	The terminal half-life (t1/2) of the 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.
Secondary	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 138 weeks.
Secondary	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.	From baseline until final study visit, up to 138 weeks.