Phase II Study to Assess AFM13 in Patients With R/R CD30-positive T-cell Lymphoma or Transformed Mycosis Fungoides
Condition: Peripheral T Cell Lymphoma; Transformed Mycosis Fungoides
MeSH terms: Mycoses; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Mycosis Fungoides
Intervention: AFM13
Intervention description: weekly intravenous infusions of 200mg
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 108.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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