GHSG-AFM13 An Open-label, Multicenter Phase II Trial With AFM13 in Patients With Relapsed or Refractory Hodgkin Lymphoma

GHSG-AFM13 An Open-label, Randomized, Multicenter Phase II Trial With AFM13 in Patients With Relapsed or Refractory Hodgkin Lymphoma

The study is designed

• to demonstrate efficacy of AFM13 with an optimized treatment schedule
• to decide whether AFM13 warrants further investigation in a phase III clinical trial

Inclusion Criteria:

• Patients with diagnosis of classical HL reconfirmed by histopathology and relapsed or refractory disease after standard therapy including brentuximab vedotin and anti-PD1 or PD-L1 antibodies
• Age: 18 years or older (both genders)
• ECOG performance status ≤2
• Life expectancy >3 months
• Measurable site of disease with ≥ 1.5cm diameter which is evaluable by CT/MRI and FDG-avid by PET
• Completion of, if applicable, radiotherapy, chemotherapy, antibodies and immunoconjugates including brentuximab vedotin and/or another investigational drug which could interact with this trial not less than 4 weeks (or 5 half-lifes of the drug, whatever occurs later) prior to first dose of study drug
• Completion of, if applicable, an autologous stem cell transplantation (ASCT) at least 3 months prior tofirst dose of study drug
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care

Exclusion Criteria:

• Any significant diseases (other than HL) 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

  • unstable angina pectoris, symptomatic congestive heart failure (NYHA II, III, IV), myocardial infarction ≤ 6 months prior to first study drug, uncontrolled cardiac arrhythmia, cerebrovascular accidents ≤ 6 months before study drug start
  • severely impaired lung function as defined by spirometry (FEV1) and DLCO (diffusing capacity of the lung for carbon monoxide) that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air
  • Liver disease as indicated by AST >3 ULN (> 5 ULN if liver involvement is present)
  • any severe or uncontrolled other disease which might increase the risk associated with study participation or study drug administration and impair the ability to evaluate the patient or for the patient to complete the study

• Major organ dysfunction (except for HL-related reduced values e.g. in case of bone marrow or organ infiltration) as indicated by

  • Absolute Neutrophil Count (ANC) ≤1.5 x 109/l
  • Platelets <75 x 109/l
  • Hemoglobin level ≤9.0 g/dl (may be maintained by transfusions)
  • Total bilirubin >2 ULN (if >2 ULN direct bilirubin is required and should be ≤1.5 x ULN); Alkaline Phosphatase >3 ULN, AST or ALT ≥3 ULN (unless due to Hodgkin Lymphoma or diagnosed Gilbert´s Syndrome)
  • Blood creatinine level >2.0 mg/dl

• History of a previous malignancy ≤3 years prior to first dose of study drug except basal or squamous cell carcinoma of the skin, cervical carcinoma in situ or completely resected melanoma in stage TNMpT1

• Patients with a history of HIV seropositivity, chronic active hepatitis, or another uncontrolled active infection within 4 weeks prior to first dose of study drug

• Patients with evidence of current central nervous system (CNS) involvement

• Prior allogeneic stem cell transplantation (SCT)

• Patients receiving systemic corticosteroid treatment > 10 mg daily prednisone equivalents or other chronic systemic immunosuppressive agents within 2 weeks prior to first dose of study drug or during study treatment

• Major surgery within 4 weeks prior to first dose of study drug

• Known hypersensitivity to recombinant proteins or any excipient in the drug formulation

• General intolerance of any protocol medication including obligatory concomitant medication

• Pregnant or nursing women or women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least 3 months thereafter. Male patients not willing to ensure that during the study and at least 3 months thereafter no fathering takes place

• Patient´s lack of accountability, inability to appreciate the nature, meaning and consequences of the trial and to formulate his/her own wishes correspondingly

• Patients unwilling to comply with the protocol

• Patients who have a relationship of dependence or employer-employee relationship to the sponsor or the investigator