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

Non-Hodgkin's Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00354926
• Other study ID #: AME 06.133v.A
• Status: Completed
• Phase: Phase 1
• First received: July 18, 2006
• Last updated: January 5, 2016
• Start date: July 2006
• Est. completion date: January 2009

Study information

• Verified date: January 2013
• Source: Applied Molecular Evolution
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 67
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Fc?RIIIa (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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma

Intervention

Biological:
• AME-133v (LY2469298)
IV 4X weekly X 4

Locations

Country	Name	City	State
United States	University of Alabama Medical Center	Birmingham	Alabama
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Rush University Medical Center	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University of Iowa	Iowa City	Iowa
United States	Nevada Cancer Institute	Las Vegas	Nevada
United States	UCLA Medical Hematology and Oncology	Los Angeles	California
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Stanford University Medical Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Applied Molecular Evolution

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events		Until the patient is off study (an average of 10 months)	No