Recruitment

Recruitment Status
Terminated
Estimated Enrollment
150

Summary

Conditions
Indolent Non-Hodgkin's Lymphoma
Type
Interventional
Phase
Phase 2
Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

Description

According to the American Cancer Society, it is estimated that approximately 70,800 individuals will be diagnosed with non-Hodgkin's lymphoma (NHL) and over 18,990 men and women will die of the disease in 2014. The survival rates for patients with indolent NHL remained unchanged from the 1950s throu...

According to the American Cancer Society, it is estimated that approximately 70,800 individuals will be diagnosed with non-Hodgkin's lymphoma (NHL) and over 18,990 men and women will die of the disease in 2014. The survival rates for patients with indolent NHL remained unchanged from the 1950s through the early 1990s, but recent evidence suggests that outcomes are improving. Indolent NHL is a particular challenge because it is an incurable disease requiring multiple treatments; yet relatively long survivals elevate the importance of quality of life associated with treatment. Agents such as rituximab are active in patients with a low burden of disease and result in high response rates and durable remissions for most patients. However, the optimal therapeutic approach to patients with low-grade lymphoma with a low disease burden is controversial as conventional chemotherapy also results in high rates of response. Regardless of whether patients receive immunotherapy, chemotherapy, or a combination thereof, they unfortunately exhibit a continuing pattern of disease relapse and the median survival for newly diagnosed patients is between 7-10 years. Rituximab and GA101 both target the CD20 antigen. The CD20 antigen is located on the surface of normal and malignant B-cell lymphocytes. An attractive feature of this target is that CD20 is not on hematopoietic stem cells, nor is it expressed in any great extent on other normal body tissues. Studies in vitro have shown that rituximab predominantly induces antibody dependent cellular cytotoxicity (ADCC), but also binds complement and directly induces apoptosis in lymphoma cells. GA101 shows increased ADCC related to an improved binding of the GA101 to the different allotypes expressed by natural killer cells and monocytes. It also has increased direct cell-death related to an elbow hinge amino acid exchange and Type II binding of the CD20 epitope. The safety of GA101 in NHL so far appears to be similar to that observed with rituximab in patients with NHL, except for a higher incidence of infusion-related reactions. Depletion of malignant B-cells using anti-CD20 monoclonal antibodies has an acceptable safety profile, particularly in patients with low-grade B-cell lymphomas with a low disease burden. To determine whether treatment with GA101 results in better outcomes than that seen with rituximab and to determine which anti-CD20 antibody to utilize in future studies, we will conduct a randomized Phase II trial of rituximab and GA101 in patients with previously untreated low-grade lymphoma. Patients will receive either rituximab or GA101 weekly for 4 weeks followed by re-staging. The endpoints of the study will be the Complete Response (CR), Overall Response Rate (ORR), time to next treatment, progression free survival (PFS), and safety of each treatment arm. PrE0401 Sub-Study Evaluation of Corrected QT (QTc) Interval and Pharmacokinetic Parameters in Patients Participating in GA101 (Obinutuzumab) Patients randomized to GA101 and who consent to the sub-study will have electrocardiograms obtained pre and post Week 1 and Week 4 to investigate the effect of GA101 on QTc interval. Pharmacokinetic blood samples will also be done to evaluate serum concentrations of GA101 at the same time-points.

Locations

Decatur, Illinois, 62526
Danville, Pennsylvania, 17822
Canton, Ohio, 44710
Mobile, Alabama, 36604
Bronx, New York, 10467
...
Decatur, Illinois, 62526
Danville, Pennsylvania, 17822
Canton, Ohio, 44710
Mobile, Alabama, 36604
Bronx, New York, 10467
Williamsport, Pennsylvania, 17701
Cleveland, Ohio, 44106
Indianapolis, Indiana, 46202
Charleston, West Virginia, 25304
Greenbrae, California, 94904
Baltimore, Maryland, 21204
La Crosse, Wisconsin, 54601
West Reading, Pennsylvania, 19611
Urbana, Illinois, 61801
Omaha, Nebraska, 68106
Madison, Wisconsin, 53717
St. Louis Park, Minnesota, 55416
Rochester, Minnesota, 55905
New Orleans, Louisiana, 70121
Toledo, Ohio, 43617
Wauwatosa, Wisconsin, 53266
Boston, Massachusetts, 02111
Philadelphia, Pennsylvania, 19111
Waukesha, Wisconsin, 53188
Ann Arbor, Michigan, 48106
Savannah, Georgia, 31405
Sioux City, Iowa, 51101
Charlottesburg, Virginia, 22908

Tracking Information

NCT #
NCT01889797
Collaborators
Genentech, Inc.
Investigators
Study Chair: Stephen Ansell, MD Mayo Clinic in Minnesota