A Study to Assess AFM13 in Patients With Hodgkin Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Affimed Therapeutics AG
ClinicalTrials.gov Identifier:
NCT01221571
First received: October 5, 2010
Last updated: June 25, 2013
Last verified: February 2011
  Purpose

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.


Condition Intervention Phase
Hodgkin Lymphoma
Drug: AFM 13
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Affimed Therapeutics AG:

Primary Outcome Measures:
  • To determine the safety and tolerability of AFM13 monotherapy. [ Time Frame: Length of Study ] [ Designated as safety issue: Yes ]
    Measure occurrence of adverse events and monitor laboratory safety parameters. Immunogenicity of AFM13.


Secondary Outcome Measures:
  • To determine the OBD (Optimal Biological Dose) or MTD (Maximum Tolerated Dose) of AFM13 [ Time Frame: Length of study ] [ Designated as safety issue: Yes ]
  • To define the pharmacokinetic profile of AFM13. [ Time Frame: Length of study ] [ Designated as safety issue: No ]
    To test levels of AFM13 in blood samples and assess curve compared to dose of AFM13 administered.

  • To analyse immunological markers of activity [ Time Frame: Length of study ] [ Designated as safety issue: No ]
    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.

  • To assess the immunogenicity of AFM13. [ Time Frame: length of study ] [ Designated as safety issue: Yes ]
  • To assess the activity of AFM13 [ Time Frame: length of study ] [ Designated as safety issue: No ]
    To measure immunological activity useing biomarkers in the blood and to measure response of the disease in FDG-PET and CT scans.


Enrollment: 28
Study Start Date: October 2010
Study Completion Date: June 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01221571

Locations
United States, Texas
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030-2374
Germany
University Hosptial Cologne
Koln, Köln, Germany, 50924 Köln
University Hospital Würzburg
Würzburg, Germany, 97080
Sponsors and Collaborators
Affimed Therapeutics AG
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
  More Information

No publications provided by Affimed Therapeutics AG

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Affimed Therapeutics AG
ClinicalTrials.gov Identifier: NCT01221571     History of Changes
Other Study ID Numbers: AFM13-101, 2010-019232-13
Study First Received: October 5, 2010
Last Updated: June 25, 2013
Health Authority: United States: Food and Drug Administration
Germany: Paul-Ehrlich-Institut

Keywords provided by Affimed Therapeutics AG:
Phase I
Dose escalation
AFM 13
Natural killer cell

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 29, 2014