Relapsed or Refractory CD30-positive Peripheral T-cell Lymphoma or Transformed Mycosis Fungoides MedDRA version: 20.0 Level: HLT Classification code 10034622 Term: Peripheral T-cell lymphomas NEC System Organ Class: 100000004851 MedDRA version: 20.0 Level: HLT Classification code 10028484 Term: Mycoses fungoides System Organ Class: 100000004851
Conditions
Interventions
Product Name: AFM13
Product Code: AFM13
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Not applicable
Current Sponsor code: AFM13
Concentration unit: mg milligram(s)
Concen
Sponsors
Affimed GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Ability to understand the purpose and risks of the study, provide signed and dated written informed consent and authorization to use confidential health information in accordance with federal, local & institutional guidelines. 2. Age =18 years at time of provision of informed consent. 3. Histologically confirmed CD30-positive (via centrally assessed Ber-H2 targeted IHC; cut-offs listed in protocol) PTCL (allowed subtypes listed in protocol) or TMF per the revised WHO 2016 classification (Swerdlow, 2016) by central assessment (Note: Subjects must wait for central results before first dose of study drug). The required cut-offs for the CD30-positivity are: • Cohort A (PTCL): =10% by IHC • Cohort B (PTCL): =1 to once per week not allowed): a) Platelet count =50,000/mm3; b) Hemoglobin =8.0 g/dL (=4.96mmol/L); c) Absolute neutrophil count >1,000/mm3; d) Alanine transaminase/aspartate transaminase = 3x the upper limit of normal (ULN) or = 5x for subjects with documented hepatic involvement with lymphoma; e) Total bilirubin =1.5 x ULN or <3 x ULN for subjects with Gilbert's disease or documented hepatic involvement with lymphoma; f) Serum creatin
Exclusion criteria
Exclusion criteria: 1. Subjects 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 gastrointestinal tract •Adult T-cell leukemia/lymphoma 2. Current evidence of central nervous system involvement. 3. Has had an allogenic tissue hematopoietic cell/solid organ transplant within the last 3 years. Note: Subjects who have had a transplant > 3 years ago are eligible as long as there are no signs/symptoms of graft versus host disease (GvHD). 4. Requirement for chronic systemic immunosuppressive therapy <12 weeks prior to the first dose of study drug for prophylaxis or management of conditions such as GvHD (eg, mycophenolate, methotrexate, calcineurin inhibitor based therapy, steroid doses that would require prolonged tapering for discontinuation). 5. Major surgery =4 weeks prior to first dose of study drug. 6. Any active, concurrent, significant illness or disease (other than T-cell lymphoma) or clinically significant findings including psychiatric and behavioral problems, medical history and/or physical examination findings that would preclude the subject from participation in the study such as: a) active infection requiring systemic therapy =10 days before the first dose of study drug; b) unstable angina pectoris, symptomatic congestive heart failure (New York Heart Association II, III, IV; Appendix C of protocol), myocardial infarction 6 months prior to first study drug, uncontrolled cardiac arrhythmia eg, atrial fibrillation/flutter, cerebrovascular accidents =6 months before first dose of study drug; c) any severe or uncontrolled other disease or condition which might increase the risk associated with study participation; d) active Hepatitis B or Hepatitis C as defined in the protocol. Antiviral prophylaxis for chronic Hepatitis B virus infection may be used at the discretion of the investigator. Note: Subjects must meet criteria defined in the protocol to be allowed to be enrolled in the study). 7. Diagnosis of Human Immunodeficiency Virus (HIV) i.e. presence of HIV 1/2 antibodies. 8. Diagnosis of immunodeficiency or requirement for systemic steroid therapy or any other form of immunosuppressive therapy (outside of examples already mentioned in exclusion criterion number 4) <7 days prior to the first dose study drug. Topical steroid creams for symptomatic relief for subjects in Cohort C (TMF) are exceptions to this rule. Also, the use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor/Medical Monitor. 9. Any other malignancy known to be active, with the exception of treated cervical intra-epithelial neoplasia and non-melanoma skin cancer. 10. General intolerance of any protocol medication or its excipients. 11. Subject´s inability to appreciate the nature, meaning and consequences of the trial and to formulate his/her own wishes correspondingly. 12. Subject is unwilling to comply with the protocol; including the required biopsies and PK sampling. 13. Prior treatment with AFM13.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To assess the antitumor activity of AFM13 by Independent Review Committee confirmed positron emission tomography-computed tomography (PET-CT)-based objective response rate (ORR);Secondary Objective: •To assess the antitumor activity of AFM13 by Independent Review Committee -confirmed complete response (CR) and partial response (PR) rates and CT scan-based ORR •To assess the antitumor activity of AFM13 by Investigator-assessed ORR (defined as ORR-2) • To assess the duration of response (DOR) to AFM13 • To assess the safety and tolerability of AFM13 • To assess the serum pharmacokinetics (PK) of AFM13 • To assess the immunogenicity of AFM13 • To assess Quality of Life of subjects while on treatment with AFM13 ;Primary end point(s): To assess the antitumor activity of AFM13 by an Independent Review Committee positron emission tomography-computed tomography (IRC-PET-CT) based objective response rate (ORR);Timepoint(s) of evaluation of this end point: ORR (CR + PR) as confirmed by an IRC as assessed by the modified Lugano Classification (Cheson, 2014) for Cohorts A and B (PTCL) based on PET-CT and after at least 8 weeks from the first assessment as assessed by Olsen Criteria (Olsen, 2011) for Cohort C (TMF)(see Appendix F of protocol). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) To assess the antitumor activity of AFM13 by: o IRC-confirmed CR and PR rates and CT scan-based ORR o Investigator-assessed ORR (defined as ORR-2) 2) To assess the duration of response (DOR) to AFM13 3) To assess the safety and tolerability of AFM13 4) To assess the pharmacokinetics (PK) of AFM13 5) To assess the immunogenicity of AFM13 6) To assess Quality of Life (QOL) of subjects while on treatment with AFM13;Timepoint(s) of evaluation of this end point: 1) At Screening and every 8 weeks for the first 3 assessments, then every 12 weeks thereafter. 2) Every 8 weeks for the first 3 assessments, then every 12 weeks thereafter. 3) Predose and at the end of each infusion (EOI), and laboratory safety evaluations. Cytokine levels in blood samples will be tested predose and EOI on Cycle 1 Day 1. 4) Evaluation of the levels of AFM13 in serum will be performed at the time points described in Schedule of Assessments (Appendix A) of the protocol. 5) Predose at Cycle 1, onwards at each Cycle on Day 1 and 29. 6) Questionnaires will be performed at Screening and at same time point as every Disease Assessment until disease progression and at Final Study Visit. | — |
Countries
Australia, France, Germany, Italy, Korea, Republic of, Poland, Russian Federation, Spain, Turkey, United States
Contacts
Public ContactMichelle Boone
ICON Clinical Research (UK) Ltd
Outcome results
None listed