A Study to Assess AFM13 in Patients With Hodgkin Lymphoma

A Pharmacodynamically-Guided Dose Escalation Phase I Study to Assess the Safety of AFM13 (Recombinant Antibody Construct Against Human CD30 and CD16A) in Patients With Refractory and/or Relapsed Hodgkin Lymphoma

The aim of this study is to determine the safety, tolerability, pharmacokinetics and activity of single cycles of AFM13 in patients with CD30 positive refractory and/or relapsed Hodgkin lymphoma.

Study Objectives:

The overall objective of this study is to determine the safety, tolerability, pharmacokinetics and activity of single cycles of AFM13 in patients with CD30 positive refractory and/or relapsed Hodgkin lymphoma.

Objectives:

1. To determine the safety and tolerability of increasing doses of single cycles of AFM13 monotherapy.
2. To determine the OBD (Optimal Biological Dose) or MTD (Maximum Tolerated Dose) of AFM13; whichever is reached first.
3. To define the pharmacokinetic profile of AFM13.
4. To analyse immunological markers e.g. ADCC (Antibody dependent cell mediated cytotoxicity), NK (Natural killer) cell activity, complement activation and depletion, and cytokine release.
5. To assess the immunogenicity of AFM13.
6. To assess the activity of AFM13.

Inclusion Criteria:

1. Histological diagnosis of relapsed or refractory Hodgkin lymphoma expressing the CD30 antigen.

2. Age ≥18 years.

3. Both genders.

4. Patients who have relapsed or are refractory after at least two prior potentially curative therapies including autologous stem cell transplantation (ASCT). Patients with a progressive disease after the first-line therapy who are ineligible for, or refused to receive high dose chemotherapy and/or ASCT for the second-line therapy, or any other established curative therapy, are also eligible.

5. Completed radiotherapy, chemotherapy, and/or treatment with other investigational agents at least 3 weeks prior to study entry.

6. Patients who received ASCT should have fully recovered prior to study entry.

7. Eastern Cooperative Oncology Group (ECOG) status of ≤2.

8. Laboratory data:

   1. Platelet count >75,000/mm3;
   2. Hemoglobin >9.0 g/dL (may be maintained by transfusion);
   3. Absolute neutrophil count >1500/mm3;
   4. ALT/AST (Alanine aminotransferase/Aspartate aminotransferase)<2.5 times the upper limit of normal (ULN);
   5. Total bilirubin <1.5 times ULN;
   6. Creatinine <1.5 mg/dL.

9. Female patients of childbearing potential who are not surgically sterile or postmenopausal and male patients who are not surgically sterile must agree to use medically effective contraception during the treatment period and up to 60 days after the last AFM13 administration. The patient must agree to sign his or her consent on this particular inclusion criterion.

10. Ability to give written, informed consent prior to any study-specific screening procedures, with the understanding that the consent may be withdrawn by the patient at any time without prejudice.

11. Be willing and able to comply with the study protocol for the duration of the study.

Exclusion Criteria:

1. Any significant diseases (other than HL (Hodgkin Lymphoma)) or clinically significant findings, including psychiatric and behavioral problems, medical history and/or physical examination findings that would preclude the patient from participating in the study.
2. History or clinical evidence of central nervous system (CNS) HL.
3. Allogeneic SCT.
4. Major surgery within 4 weeks prior to study entry.
5. Known hypersensitivity to recombinant proteins or any excipient contained in the drug formulation.
6. Known history of another primary malignancy that has not been in remission for at least 5 years. Non-concurrent non-melanoma skin cancer and cervical carcinoma in situ or squamous intraepithelial lesions (e.g., cervical intraepithelial neoplasia [CIN] or prostatic intraepithelial/intraductal neoplasia [PIN]) are allowed.
7. Any active viral, bacterial, or systemic fungal infection within 4 weeks prior to study entry.
8. Known to be positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg), or hepatitis C virus (HCV).
9. History of significant chronic or recurrent infections requiring treatment.
10. Receiving systemic steroid prednisone or equivalent during the 3 weeks immediately preceding enrollment.
11. Pregnant or breast-feeding.