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

Sponsor

Applied Molecular Evolution (Industry)

Overall Status

Completed

CT.gov ID

NCT00354926

Collaborator

(none)

Enrollment

Locations

Arm

30.1

Duration (Months)

6.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is designed to provide evidence of the safety and a preliminary understanding of the efficacy of AME 133v.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin's Lymphoma	Biological: AME-133v (LY2469298)	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

67 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jul 1, 2006

Actual Primary Completion Date :

Jan 1, 2009

Actual Study Completion Date :

Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
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.	Biological: AME-133v (LY2469298) IV 4X weekly X 4

Arm

Intervention/Treatment

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.

Biological: AME-133v (LY2469298)

IV 4X weekly X 4

Outcome Measures

Primary Outcome Measures

Adverse Events [Until the patient is off study (an average of 10 months)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Absolute neutrophil count greater than 1,500/mm³;
Platelet count greater than 75,000/mm³;
Hemoglobin at least 8 g/dL;
Serum creatinine ≤ 1.5x upper limit of normal;
Total bilirubin ≤ 1.5x upper limit of normal;
ALT ≤ 1.5 x upper limit of normal;
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama Medical Center	Birmingham	Alabama	United States	35249
2	UCLA Medical Hematology and Oncology	Los Angeles	California	United States	90095
3	Stanford University Medical Center	Stanford	California	United States	94305
4	Rush University Medical Center	Chicago	Illinois	United States	60612
5	University of Iowa	Iowa City	Iowa	United States	52242
6	Nevada Cancer Institute	Las Vegas	Nevada	United States	89135
7	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
8	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
9	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15232
10	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
11	University of Virginia Health System	Charlottesville	Virginia	United States	22908

Sponsors and Collaborators

Applied Molecular Evolution

Investigators

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