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Safety and Efficacy Study of an Anti-CD20 Monoclonal Antibody (AME-133v) to Treat Non-Hodgkin's Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00354926
Recruitment Status : Completed
First Posted : July 20, 2006
Last Update Posted : January 7, 2016
Sponsor:
Information provided by (Responsible Party):
Applied Molecular Evolution

Tracking Information
First Submitted Date  ICMJE July 18, 2006
First Posted Date  ICMJE July 20, 2006
Last Update Posted Date January 7, 2016
Study Start Date  ICMJE July 2006
Actual Primary Completion Date January 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 5, 2016)
Adverse Events [ Time Frame: Until the patient is off study (an average of 10 months) ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 18, 2006)
Adverse events and laboratory evaluations
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2006)
Pharmacokinetic analysis and tumor evaluation by International Workshop criteria
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of an Anti-CD20 Monoclonal Antibody (AME-133v) to Treat Non-Hodgkin's Lymphoma
Official Title  ICMJE Open-Label, Multicenter, Phase 1/2 Dose-Escalation Study of AME-133v (LY 2469298), Administered Intravenously in Four Weekly Doses, in Subjects With CD20+ Follicular Relapsed or Refractory Non-Hodgkin's Lymphoma
Brief Summary This study is designed to provide evidence of the safety and a preliminary understanding of the efficacy of AME 133v.
Detailed Description The protein engineering of AME-133v is hypothesized to result in an anti-CD20 therapy with greater potency and efficacy in all patients, but particularly in genetically defined subpopulations that respond poorly to rituximab because they express a low affinity version of the Fc receptor on their immune effector cells. A monoclonal antibody that has increased binding for this receptor should be more effective in stimulating effector cell killing and thus improve response to the antibody.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Hodgkin's Lymphoma
Intervention  ICMJE Biological: AME-133v (LY2469298)
IV 4X weekly X 4
Study Arms  ICMJE Experimental: AME 133v
All subjects will receive weekly intravenous infusions of AME-133v. Each subject will receive a total of 4 infusions administered once a week for 3 consecutive weeks.
Intervention: Biological: AME-133v (LY2469298)
Publications * Ganjoo KN, de Vos S, Pohlman BL, Flinn IW, Forero-Torres A, Enas NH, Cronier DM, Dang NH, Foon KA, Carpenter SP, Slapak CA, Link BK, Smith MR, Mapara MY, Wooldridge JE. Phase 1/2 study of ocaratuzumab, an Fc-engineered humanized anti-CD20 monoclonal antibody, in low-affinity FcγRIIIa patients with previously treated follicular lymphoma. Leuk Lymphoma. 2015 Jan;56(1):42-8. doi: 10.3109/10428194.2014.911859. Epub 2014 Jul 14.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 28, 2013)
67
Original Enrollment  ICMJE
 (submitted: July 18, 2006)
80
Actual Study Completion Date  ICMJE January 2009
Actual Primary Completion Date January 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

To be included in the study protocol, subjects have to meet all of the following criteria.

  • Have morphologically confirmed diagnosis of CD-20+ follicular B-cell non-Hodgkin's lymphoma;
  • Have the low affinity form of FcγRIIIa (F/F or F/V at position 158) as determined by FcR genotyping;
  • Have measurable disease. Measurable masses (such as enlarged lymph nodes) must have a clearly defined bi-dimensional diameter of at least 1.5 x 1.5 cm on physical examination or ≤ 1.5 cm in one of the dimensions by CT, MRI, or plain radiograph;
  • Have received prior treatment with chemotherapy given without rituximab; OR, Have not relapsed or progressed within 120 days (inclusive) of the last infusion of rituximab;
  • Be 18 years of age or greater;
  • Have a negative pregnancy test, if relevant. Women of childbearing potential (not postmenopausal for at least one year and not surgically incapable of bearing children) must agree not to become pregnant for the duration of the study. To do this, they must agree to use a medically acceptable contraceptive regimen;
  • Have a performance status of 0 to 2 on the ECOG performance scale;
  • Have adequate hematopoietic, renal, and hepatic function defined as:

    1. Absolute neutrophil count greater than 1,500/mm³;
    2. Platelet count greater than 75,000/mm³;
    3. Hemoglobin at least 8 g/dL;
    4. Serum creatinine ≤ 1.5x upper limit of normal;
    5. Total bilirubin ≤ 1.5x upper limit of normal;
    6. ALT ≤ 1.5 x upper limit of normal;
    7. Alkaline phosphatase ≤ 1.5x upper limit of normal.
  • No evidence of hepatitis B or C infection (no detectable HBV DNA or HCV RNA);
  • Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, or other investigational therapy for at least 30 days prior to study enrollment;
  • Have discontinued all high-dose corticosteroid therapy at least 30 days prior to study enrollment (≤ 10 mg/day of Prednisone or equivalent is allowable);
  • Have life expectancy of more than 3 months;
  • Be able to give written informed consent.

Exclusion Criteria:

Subjects with any of the following exclusions are not allowed to participate in the study.

  • Allergy to monoclonal antibodies or any of the study drug components;
  • Concurrent malignancy that could complicate interpretation of response evaluation, including any histologic evidence of diffuse B-cell lymphoma. Non-melanoma skin cancer and carcinoma in situ of the cervix are not exclusions;
  • Significant cardiac disease (e.g. NYHA CHF of class III or IV, history of MI within one year prior to study Day 1, unstable angina, uncontrolled hypertension, clinically significant cardiac arrhythmia (CTCAE Grade 2 or higher), or clinically significant baseline ECG or MUGA abnormality.
  • Positive test for serum cardiac troponins (cTnI or cTnT assay; special processing required, and the same assay must be used throughout the study; see Study Reference Manual)
  • Active infection requiring oral or i.v. antibiotics;
  • Administration of blood transfusions or red blood cell growth factors within 10 days preceding enrollment into the protocol;
  • Administration of white cell growth factors within 28 days preceding enrollment into the protocol;
  • Concomitant nonmalignant disease(s) which could interfere with implementation of the protocol, make the study results difficult to interpret, or which represent additional safety risks;
  • History of HIV-associated non-Hodgkin's lymphoma.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00354926
Other Study ID Numbers  ICMJE AME 06.133v.A
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Applied Molecular Evolution
Study Sponsor  ICMJE Applied Molecular Evolution
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Brian Link, MD University of Iowa
Principal Investigator: Andres Forero-Torres, MD University of Alabama Medical Center
Principal Investigator: Nam Dang, MD Nevada Cancer Institute
Principal Investigator: Sven de Vos, MD, PhD University of California, Los Angeles
Principal Investigator: Kristen Ganjoo, MD Stanford University
Principal Investigator: Brad Pohlman, MD The Cleveland Clinic
Principal Investigator: Mitchell R. Smith, MD, PhD Fox Chase Cancer Center
Principal Investigator: Michael E. Williams, MD University of Virginia Health Systems
Principal Investigator: Ian Flinn, MD, PhD SCRI Development Innovations, LLC
Principal Investigator: Markus Mapara, MD, PhD University of Pittsburgh Medical Center
Principal Investigator: Stephanie A. Gregory, MD Rush University Medical Center
PRS Account Applied Molecular Evolution
Verification Date January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP