A study to evaluate the safety and efficacy of AFM13 in patients with certain types of T-cell lymphoma
- Conditions
- Relapsed or Refractory CD30-positive Peripheral T-cell Lymphoma or Transformed Mycosis FungoidesMedDRA version: 20.0Level: HLTClassification code 10034622Term: Peripheral T-cell lymphomas NECSystem Organ Class: 100000004851MedDRA version: 20.0Level: HLTClassification code 10028484Term: Mycoses fungoidesSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-001003-20-DE
- Lead Sponsor
- Affimed GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 108
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 <10% by IHC
• Cohort C (TMF): =1% by IHC
Measurable disease will be defined as below for each cohort:
• 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.
• 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. Note: After the planned Interim Analyses, Cohorts A and B may be combined with the CD30-positivity defined as = 1% by centrally assessed IHC.
4. Subjects must have relapsed or refractory disease AND the following:
• Cohorts A and B (PTCL cohorts): Subjects must have received at least 1 prior line of systemic therapy. For subjects with systemic ALCL, subjects must have failed or be intolerant to brentuximab vedotin [BV]; Adcetris®.
• Cohort C (TMF cohort): Subjects must have received at least 1 prior line of systemic therapy, and have exhausted systemic therapies with full approval for their treatment of transformed mycosis fungoides.
Note: intolerance is defined as a discontinuation of a drug due to a = Grade 2 treatment-related adverse event that is clearly documented.
5. Completion of treatment with any radiotherapy, chemotherapy, antibody, immunoconjugates and/or another investigational drug =4 weeks (or 5 half-lives of the drug, whichever is shorter) prior to first dose of study drug.
Note: Subjects may be enrolled after a minimum of 2 weeks post radiation if radiation was for palliative intent to a single cutaneous lesion or single nodal region after discussion with the Sponsor.
6. Completion of an autologous hematopoietic stem cell transplantation at least 3 months prior to first dose of study drug (if applicable).
7. Resolution of any clinically significant previous therapy-related toxicity to =Grade 1 or to baseline if pre-existing condition (exception: Subjects with all grade alopecia and =Grade 2 peripheral neuropathy).
8. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.
9. Life expectancy =12 weeks.
10. Adequate laboratory functional values. (Note: transfusions and growth factors allowed during Screening; however, transfusion dependency defined as requiring blood products > 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
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method