Clinical trial NCT01221571: A Study to Assess AFM13 in Patients With Hodgkin Lymphoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hodgkin Lymphoma
Keywords: Phase I
Dose escalation
AFM 13
Natural killer cell
Lead sponsor: Affimed GmbH
Sponsor class: INDUSTRY
First posted: 2010-10-15
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: To determine the safety and tolerability of AFM13 monotherapy.
timeFrame: Length of Study
Secondary outcomes:
measure: To determine the OBD (Optimal Biological Dose) or MTD (Maximum Tolerated Dose) of AFM13
timeFrame: Length of study
measure: To define the pharmacokinetic profile of AFM13.
timeFrame: Length of study
measure: To analyse immunological markers of activity
timeFrame: Length of study
measure: To assess the immunogenicity of AFM13.
timeFrame: length of study
measure: To assess the activity of AFM13
timeFrame: length of study
Other outcomes:
Locations:
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Koln
country: Germany
facility: University Hosptial Cologne
state: Köln
city: Würzburg
country: Germany
facility: University Hospital Würzburg
Study officials:
affiliation: University Hospital Cologne, Germany
name: Andreas Engert, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: MD Anderson Cancer Center, Houston, Texas
name: Anas Younes, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Würzburg, Germany
name: Max S Topp, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.