Phase II Study to Assess AFM13 in Patients With R/R CD30-positive T-cell Lymphoma or Transformed Mycosis Fungoides
- Conditions
- Peripheral T Cell LymphomaTransformed 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
- 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
- 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 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).
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 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).
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).
Trial Locations
- Locations (69)
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, 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
Emory University Clinic/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
University of Michigan Health | Rogel Cancer Center
🇺🇸Ann Arbor, Michigan, 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 Washington Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
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
Centre Hospitalier Universitaire (CHU) de Bordeaux
🇫🇷Bordeaux, France
Linear Clinical Research
🇦🇺Nedlands, Australia
Centre Hospitalier Universitaire de Brest
🇫🇷Brest, France
CHD Vendée
🇫🇷La Roche Sur Yon, France
CHU Pontchaillou
🇫🇷Rennes, France
Institut Gustave Roussy
🇫🇷Villejuif, France
University Hospital Leipzig
🇩🇪Leipzig, Germany
Kliniken Essen Sued - Evangelisches Krankenhaus Essen-Werden gGmbH
🇩🇪Essen, Germany
Universitaetsmedizin Mainz
🇩🇪Mainz, Germany
Rotkreuzklinikum Muenchen
🇩🇪Muenchen, Germany
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
Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego
🇵🇱Warsaw, Poland
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu. Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku
🇵🇱Wrocław, Poland
Instytut Hematologii i Transfuzjologii, Klinika Hematologii
🇵🇱Warsaw, Poland
Republic Hospital n.a. V.A. Baranov
🇷🇺Petrozavodsk, Russian Federation
First State Saint-Petersburg Pavlov Medical University
🇷🇺Saint Petersburg, Russian Federation
Russian Research Institute of Hematology and Transfusiology of the Federal Biomedical Agency
🇷🇺St. Petersburg, Russian Federation
Regional Clinical Hospital
🇷🇺Tula, Russian Federation
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 Virgen del Rocio
🇪🇸Sevilla, Spain
Institut Catala d'Oncologia Tarragona
🇪🇸Tarragona, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre-Centro de Actividades Ambulatorias
🇪🇸Madrid, Spain
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
🇹🇷Ankara, Turkey
Istanbul Universitesi Istanbul Tip Fakultesi Ic Hastaliklari Anabilim Dali Hematoloji Bilim Dali Fatih
🇹🇷Istanbul, Turkey
Ege University Medical Faculty
🇹🇷İzmir, Turkey
Kocaeli University Faculty of Medicine, Department of Internal Diseases, Hematology Division
🇹🇷İzmit, 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, Turkey
Szpitale Pomorskie Sp. z o.o.. Szpital Morski im. PCK, Oddzial Hematologii i Transplantologii Szpiku
🇵🇱Gdynia, Poland
Pratia MCM Krakow
🇵🇱Kraków, Poland
Saratov State Medical University
🇷🇺Saratov, Russian Federation
GUZ Leningrad Regional Clinical Hospital
🇷🇺St. Petersburg, Russian Federation
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, Italy
University of Alabama at Birmingham (O'Neal Comprehensive Cancer Center)
🇺🇸Birmingham, Alabama, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States