A study to evaluate the safety and efficacy of AFM13 in patients with certain types of T-cell lymphoma

Phase 1

Conditions: Relapsed or Refractory CD30-positive Peripheral T-cell Lymphoma or Transformed Mycosis Fungoides
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2019-001003-20-PL

Lead Sponsor: Affimed GmbH

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 108

Inclusion Criteria

1. Written informed consent in accordance with federal, local, and
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 PTCL subtypes allowed for Cohorts A and B as described in protocol
section 3.1. The required cut-offs for the CD30-positivity are described in protocol
section 3.1.
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 (=4.96 mmol/L);
c) Absolute neutrophil count >1,000/mm3;
d) Alanine transaminase/aspartate transaminase =3 x the upper limit of
normal (ULN) or =5 x 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 c

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.

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

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