Clinical Trials

Inclusion Criteria:

• Histologically confirmed CD30-positive PTCL (most subtypes allowed) or TMF per the revised World Health Organization 2016 classification (Swerdlow, 2016).
  Note: Patients must wait for central results before first dose of study drug.
• 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: Confirmation by 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 cohorts):
  • 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 cohort):
  • patients 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 
• 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: patients may be enrolled after a minimum of 2 weeks of radiation if radiation was for palliative intent to a single cutaneous lesion or single nodal region after discussion with the sponsor.
• Completion of an autologous hematopoietic stem cell transplantation at least 3 months prior to first dose of study drug (if applicable). 
• Resolution of any clinically significant previous therapy-related toxicity to ≤Grade 1 or to baseline if pre-existing condition (exception: patients with all grade alopecia and ≤Grade 2 peripheral neuropathy.
• Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 (Appendix B).
• Life expectancy ≥12 weeks.
• Adequate laboratory functional values. Note: transfusions and growth factors allowed during screening; however, transfusion-dependency defined as requiring blood products ≥once per week is not allowed.

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.
  • Adult T-cell leukemia/lymphoma (ATLL)
• Current evidence of central nervous system involvement.
• 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 chronic systemic immunosuppressive therapy <12 weeks prior to the first dose of study drug for prophylaxis or management of conditions such as GvHD (e.g. mycophenolate, methotrexate, calcineurin inhibitor-based therapy, steroid doses that would require prolonged tapering for discontinuation).
• Major surgery ≤4 weeks prior to first dose of study drug.
• 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 patient from participation in the study such as:
  • active infection requiring systemic therapy ≤10 days before the first dose of study drug
  • unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to first study drug, uncontrolled cardiac arrhythmia e.g. atrial fibrillation/flutter, cerebrovascular accidents ≤6 months before first dose of study drug
  • any severe or uncontrolled other disease or condition which might increase the risk associated with study participation
  • active Hepatitis B or Hepatitis C. Antiviral prophylaxis for chronic Hepatitis B virus infection may be used at the discretion of the investigator.
• Diagnosis of Human Immunodeficiency Virus (HIV) i.e. presence of HIV 1/2 antibodies
• Diagnosis of immunodeficiency or requirement for systemic steroid therapy or any other form of immunosuppressive therapy (outside of samples already mentioned in Exclusion Criterion number 4) <7 days prior to the first dose study drug. Topical steroid creams for symptomatic relief for patients 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.
• Any other malignancy known to be active, with the exception of treated cervical intraepithelial neoplasia and non-melanoma skin cancer.
• General intolerance of any protocol medication or its excipients
• Patient´s inability to appreciate the nature, meaning and consequences of the trial and to formulate his/her own wishes correspondingly.
• Patient is unwilling to comply with the protocol; including the required biopsies and PK sampling.
• Prior treatment with AFM13.