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 Overview

• Status: Completed
• Conditions: Hodgkin Lymphoma
• Intervention / Treatment: Drug: AFM 13

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Würzburg, Germany, 97080
    • University Hospital Würzburg
  • Köln
    • Koln, Köln, Germany, 50924 Köln
      • University Hosptial Cologne
• United States
  • Texas
    • Houston, Texas, United States, 77030-2374
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AFM13; IV (intravenous) infusion, dose escalation	Drug: AFM 13; Cohort escalation then expansion phase design. Starting dose 0.01 mg/kg. 4 weekly drug administrations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the safety and tolerability of AFM13 monotherapy.	Measure occurrence of adverse events and monitor laboratory safety parameters. Immunogenicity of AFM13.	Length of Study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the OBD (Optimal Biological Dose) or MTD (Maximum Tolerated Dose) of AFM13		Length of study
To define the pharmacokinetic profile of AFM13.	To test levels of AFM13 in blood samples and assess curve compared to dose of AFM13 administered.	Length of study
To analyse immunological markers of activity	ADCC, NK cell, Complement and Cytokine levels in the serum will be measured at different time points to assess the level of activity resulting from administration of AFM13.	Length of study
To assess the immunogenicity of AFM13.		length of study
To assess the activity of AFM13	To measure immunological activity useing biomarkers in the blood and to measure response of the disease in FDG-PET and CT scans.	length of study

Collaborators and Investigators

• Sponsor: Affimed GmbH
• Investigators: Principal Investigator: Andreas Engert, Professor, University Hospital Cologne, Germany; Principal Investigator: Anas Younes, Professor, MD Anderson Cancer Center, Houston, Texas; Principal Investigator: Max S Topp, Professor, University Hospital Würzburg, Germany

Publications and helpful links

General Publications

• Rothe A, Sasse S, Topp MS, Eichenauer DA, Hummel H, Reiners KS, Dietlein M, Kuhnert G, Kessler J, Buerkle C, Ravic M, Knackmuss S, Marschner JP, Pogge von Strandmann E, Borchmann P, Engert A. A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2015 Jun 25;125(26):4024-31. doi: 10.1182/blood-2014-12-614636. Epub 2015 Apr 17.
• Reiners KS, Kessler J, Sauer M, Rothe A, Hansen HP, Reusch U, Hucke C, Kohl U, Durkop H, Engert A, von Strandmann EP. Rescue of impaired NK cell activity in hodgkin lymphoma with bispecific antibodies in vitro and in patients. Mol Ther. 2013 Apr;21(4):895-903. doi: 10.1038/mt.2013.14. Epub 2013 Mar 5.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: October 5, 2010
• First Submitted That Met QC Criteria: October 14, 2010
• First Posted (Estimate): October 15, 2010

Study Record Updates

• Last Update Posted (Estimate): June 26, 2013
• Last Update Submitted That Met QC Criteria: June 25, 2013
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: Phase I; Dose escalation; AFM 13; Natural killer cell
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease
• Other Study ID Numbers: AFM13-101; 2010-019232-13 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No