Clinical trial NCT00354926: Safety and Efficacy Study of an Anti-CD20 Monoclonal Antibody (AME-133v) to Treat Non-Hodgkin's Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-Hodgkin's Lymphoma
Keywords: Non-Hodgkin's Lymphoma
rituximab
humanized monoclonal antibody
anti-CD20 monoclonal antibody
Lead sponsor: Applied Molecular Evolution
Sponsor class: INDUSTRY
First posted: 2006-07-20
Enrollment: 67
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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse Events
timeFrame: Until the patient is off study (an average of 10 months)
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Medical Center
state: Alabama
city: Los Angeles
country: United States
facility: UCLA Medical Hematology and Oncology
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Las Vegas
country: United States
facility: Nevada Cancer Institute
state: Nevada
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
Study officials:
affiliation: University of Iowa
name: Brian Link, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama Medical Center
name: Andres Forero-Torres, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nevada Cancer Institute
name: Nam Dang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: Sven de Vos, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Kristen Ganjoo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Brad Pohlman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fox Chase Cancer Center
name: Mitchell R. Smith, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Virginia Health Systems
name: Michael E. Williams, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: SCRI Development Innovations, LLC
name: Ian Flinn, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh Medical Center
name: Markus Mapara, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rush University Medical Center
name: Stephanie A. Gregory, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 FcgammaRIIIa patients with previously treated follicular lymphoma. Leuk Lymphoma. 2015 Jan;56(1):42-8. doi: 10.3109/10428194.2014.911859. Epub 2014 Jul 14.