Clinical trial NCT04101331: Phase II Study to Assess AFM13 in Patients With R/R CD30-positive T-cell Lymphoma or Transformed Mycosis Fungoides
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Peripheral T Cell Lymphoma
Transformed Mycosis Fungoides
Lead sponsor: Affimed GmbH
Sponsor class: INDUSTRY
First posted: 2019-09-24
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Overall Response Rate Assessed by Independent Review Committee Based on PET-CT
timeFrame: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 28 months).
Secondary outcomes:
measure: Overall Response Rate Assessed by Investigator Based on PET-CT
timeFrame: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 46 months).
measure: Overall Response Rate Assessed by Investigator Based on CT
timeFrame: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 46 months).
measure: Complete Response Rate and Partial Response Rate Assessed by Independent Review Committee Based on PET-CT
timeFrame: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 46 months).
measure: Complete Response Rate, Partial Response Rate and Overall Response Rate Assessed by Independent Review Committee Based on CT
timeFrame: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 46 months).
measure: Duration of Overall Response Assessed by Independent Review Committee Based on PET-CT
timeFrame: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 46 months).
measure: Duration of Overall Response Assessed by Independent Review Committee Based on CT
timeFrame: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 46 months).
measure: Duration of Overall Response Assessed by Investigator Based on PET-CT
timeFrame: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 46 months).
measure: Duration of Overall Response Assessed by Investigator Based on CT
timeFrame: Tumor assessment performed every 8 weeks for first 3 assessments, then every 12 weeks until documented disease progression (up to 46 months).
measure: Number of Subjects With Treatment Related Adverse Event
timeFrame: From the date of first treatment until the date of the last treatment + 37 days, up to 199 weeks.
measure: Maximum Measured Concentration (Cmax) of AFM13
timeFrame: 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.
measure: Area Under the Concentration-Time Curve of AFM13 From 0 to Infinity (AUC 0-∞)
timeFrame: 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.
measure: Volume of Distribution at Steady State (Vss) of AFM13
timeFrame: 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.
measure: The Terminal Half-life (t1/2) of AFM13
timeFrame: 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.
measure: European Quality of Life 5-dimensional Pain/Discomfort Score (EQ-5D)
timeFrame: At baseline and final study visit, up to 199 weeks.
measure: European Quality of Life 5-dimensional Visual Analogue Scale Scores (EQ-5D)
timeFrame: From baseline until final study visit, up to 199 weeks.
measure: Number of Subjects Who Developed Anti-drug Antibodies (ADA) During Treatment
timeFrame: Pre-dose Day 1 on cycle 1 and end of treatment, up to approximately 46 months.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham (O'Neal Comprehensive Cancer Center)
state: Alabama
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles (UCLA) Health
state: California
city: Atlanta
country: United States
facility: Emory University Clinic/Winship Cancer Institute
state: Georgia
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation/Precision Cancer Therapies Program
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan Health | Rogel Cancer Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Center for Lymphoid Malignancies
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: University of Washington Seattle Cancer Care Alliance
state: Washington
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
city: Clayton
country: Australia
facility: Monash Health-Monash Medical Centre
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
city: Gosford
country: Australia
facility: Gosford Hospital
city: Nedlands
country: Australia
facility: Linear Clinical Research
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire (CHU) de Bordeaux
city: Brest
country: France
facility: Centre Hospitalier Universitaire de Brest
city: La Roche Sur Yon
country: France
facility: CHD Vendée
city: Rennes
country: France
facility: CHU Pontchaillou
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Essen
country: Germany
facility: Kliniken Essen Sued - Evangelisches Krankenhaus Essen-Werden gGmbH
city: Leipzig
country: Germany
facility: University Hospital Leipzig
city: Mainz
country: Germany
facility: Universitaetsmedizin Mainz
city: Muenchen
country: Germany
facility: Rotkreuzklinikum Muenchen
city: Bologna
country: Italy
facility: Ist.Ematologia E Oncologia Medica L.E A.Seragnoli
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS
city: Milano
country: Italy
facility: Azienda Ospedaliera Niguarda Ca' Granda
city: Ravenna
country: Italy
facility: Azienda Unita Sanitaria Locale di Ravenna - Ospedale S. Maria delle Croci di Ravenna
city: Jeonju
country: Korea, Republic of
facility: Chonbuk National University Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Catholic University of Korea, Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp. z o.o.. Szpital Morski im. PCK, Oddzial Hematologii i Transplantologii Szpiku
city: Kraków
country: Poland
facility: Pratia MCM Krakow
city: Warsaw
country: Poland
facility: Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie, Klinika Nowotworow Ukladu Chlonnego
city: Warsaw
country: Poland
facility: Instytut Hematologii i Transfuzjologii, Klinika Hematologii
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu. Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku
city: Petrozavodsk
country: Russian Federation
facility: Republic Hospital n.a. V.A. Baranov
city: Saint Petersburg
country: Russian Federation
facility: First State Saint-Petersburg Pavlov Medical University
city: Saratov
country: Russian Federation
facility: Saratov State Medical University
city: St. Petersburg
country: Russian Federation
facility: GUZ Leningrad Regional Clinical Hospital
city: St. Petersburg
country: Russian Federation
facility: Russian Research Institute of Hematology and Transfusiology of the Federal Biomedical Agency
city: Tula
country: Russian Federation
facility: Regional Clinical Hospital
city: Barcelona
country: Spain
facility: Duran I Reynals Hospital Catalan Institute Of Oncology
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia Badalona, Hospital Germans Trias I Pujol
city: Girona
country: Spain
facility: Institut Catala d' Oncologia Girona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre-Centro de Actividades Ambulatorias
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Tarragona
country: Spain
facility: Institut Catala d'Oncologia Tarragona
city: Ankara
country: Turkey
facility: Ankara University Faculty of Medicine, Department of Internal Diseases, Hematology Division
city: Ankara
country: Turkey
facility: Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim Arastirma Hastanesi Hematoloji Klinigi Ankara
city: Ankara
country: Turkey
facility: Gazi University Faculty of Medicine, Department of Internal Diseases
city: Ankara
country: Turkey
facility: Sağlık Bilimleri Üniversitesi Gülhane Eğitim ve Araştırm Hastanesi
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Istanbul Tip Fakultesi Ic Hastaliklari Anabilim Dali Hematoloji Bilim Dali Fatih
city: İzmir
country: Turkey
facility: Ege University Medical Faculty
city: İzmit
country: Turkey
facility: Kocaeli University Faculty of Medicine, Department of Internal Diseases, Hematology Division
city: Samsun
country: Turkey
facility: Ondokuz Mayis Universitesi Tip Fakultesi Saglik Uyg. ve Egitim Merkezi
city: Tekirdag
country: Turkey
facility: Tekirdag Namik Kemal Universitesi Saglik Uygulama ve Arastirma Hastanesi
city: Trabzon
country: Turkey
facility: KaradenizTeknik Universitesi Tip Fakultesi Farabi Hastanesi
Study officials:
affiliation: Affimed Inc.
name: Karenza Alexis, MD
role: STUDY_DIRECTOR
affiliation: Samsung Medical Center
name: Won Seog Kim, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Sloan Kettering Cancer Center
name: Steven Horwitz, MD
role: PRINCIPAL_INVESTIGATOR
References: