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

Sponsor

Affimed GmbH (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04101331

Collaborator

(none)

145

Enrollment

Locations

Arms

48.6

Anticipated Duration (Months)

2.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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 objective 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.

Condition or Disease	Intervention/Treatment	Phase
Peripheral T Cell Lymphoma Transformed Mycosis Fungoides	Drug: AFM13	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

145 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Nov 13, 2019

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A PTCL (peripheral T cell lymphoma) patients with CD30 expression ≥10%	Drug: AFM13 weekly intravenous infusions of 200mg
Experimental: Cohort B PTCL (peripheral T cell lymphoma) patients with CD30 expression ≥1% to <10%	Drug: AFM13 weekly intravenous infusions of 200mg
Experimental: Cohort C TMF (transformed mycosis fungoides) patients with CD30 expression ≥1%	Drug: AFM13 weekly intravenous infusions of 200mg

Arm

Intervention/Treatment

Experimental: Cohort A

PTCL (peripheral T cell lymphoma) patients with CD30 expression ≥10%

Drug: AFM13

weekly intravenous infusions of 200mg

Experimental: Cohort B

PTCL (peripheral T cell lymphoma) patients with CD30 expression ≥1% to <10%

Drug: AFM13

weekly intravenous infusions of 200mg

Experimental: Cohort C

TMF (transformed mycosis fungoides) patients with CD30 expression ≥1%

Drug: AFM13

weekly intravenous infusions of 200mg

Outcome Measures

Primary Outcome Measures

Antitumor activity of AFM13: Independent Review Committee (IRC)-confirmed objective response rate (ORR) [From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months]
Assessed by the modified Lugano Classification (Cheson, 2014) for Cohorts A and B (PTCL) and after at least 8 weeks from the first assessment as assessed by Olsen Criteria (Olsen, 2011) for Cohort C (TMF)

Secondary Outcome Measures

Antitumor activity of AFM13: Investigator-assessed objective response rate (ORR-2) [From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months]
Assessed by the modified Lugano Classification (Cheson, 2014) for Cohorts A and B (PTCL) and after at least 8 weeks from the first assessment as assessed by Olsen Criteria (Olsen, 2011) for Cohort C (TMF)
Duration of response to AFM13 (DOR) [From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months]
Assessed by the modified Lugano Classification (Cheson, 2014) for Cohorts A and B (PTCL) and after at least 8 weeks from the first assessment as assessed by Olsen Criteria (Olsen, 2011) for Cohort C (TMF )
Safety of AFM13 [From screening till final study visit (30-37 days after last dose)]
Number and frequency of Adverse Events, which includes clinical significant abnormal findings in safety laboratory, vital signs and ECG assessments.
Pharmacokinetics (PK) of AFM13 [During Cycle 1 (each cycle is 56 days)]
Cmax (maximum measured concentration of the analyte in plasma)
PK of AFM13 [During Cycle 1 (each cycle is 56 days)]
AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
PK of AFM13 [During Cycle 1 (each cycle is 56 days)]
Vss (Volume of distribution at steady state)
PK of AFM13 [During Cycle 1 (each cycle is 56 days)]
t1/2 (Terminal half-life)
Immunogenicity of AFM13 [From screening till final study visit (30-37 days after last dose)]
Maximum change from baseline of anti-drug antibodies (ADA) in blood and their neutralizing potential
Quality of Life (QoL) [Through study completion, up to 12 months]
QoL as measured by the European Quality of Life 5-dimensional questionnaire (EQ-5D) for Cohorts A and B; and by Skindex-29 for Cohort C

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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

Sponsors and Collaborators

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