A Randomized Phase II Trial of Ofatumumab and Bendamustine vs. Ofatumumab, Bortezomib (NSC # 681239, IND # 58443) and Bendamustine in Patients With Untreated Follicular Lymphoma
PRIMARY OBJECTIVES:
I. To determine the complete response (CR) rate in newly diagnosed, untreated follicular
lymphoma patients receiving 6 cycles of ofatumumab-bendamustine (ARM A) and 6 cycles of
ofatumumab, bortezomib, and bendamustine (ARM B) using International Harmonization Project
Response Criteria.
SECONDARY OBJECTIVES:
I. To determine progression-free survival (PFS) of patients with untreated follicular
lymphoma after 6 cycles of ofatumumab-bendamustine (ARM A) followed by maintenance
ofatumumab and after 6 cycles of ofatumumab, bortezomib, and bendamustine followed by
maintenance ofatumumab and bortezomib (ARM B).
II. To determine the toxicity profile of ofatumumab and bendamustine and ofatumumab,
bortezomib, and bendamustine in patients with untreated high-risk follicular lymphoma.
III. To determine if changes in both qualitative and semi-quantitative fludeoxyglucose
(FDG)-positron-emission tomography (PET) findings at baseline, after cycle 2 (day 32-35),
and at end of therapy (6-8 weeks after the last cycle of induction chemotherapy but prior to
maintenance therapy) with ofatumumab-bendamustine and ofatumumab, bortezomib, and
bendamustine correlate with response and PFS in patients with high-risk follicular lymphoma.
IV. To assess if a combinatorial approach using both qualitative and semiquantitative
changes in FDG-PET and computed tomography (CT) or magnetic resonance imaging (MRI) studies
at baseline, after cycle 2 (day 32-35), and at end of therapy (6-8 weeks after the last
cycle of induction chemotherapy prior to maintenance therapy) would result in a higher
predictive value for response and PFS in patients with high-risk follicular lymphoma.
V. To correlate all molecular parameters with FDG-PET parameters in determination of
response and PFS.
VI. To correlate pre-treatment single nucleotide polymorphisms with response and PFS
following ofatumumab-bendamustine and ofatumumab, bortezomib, and bendamustine therapy in
patients with untreated high-risk follicular lymphoma.
VII. To correlate CD-68, bcl-2, Ki-67, FOXP3, activated cytotoxic T-cells,
lymphoma-associated macrophages (LAM), MUM1, CD10, nuclear p65 and cREL subunits of NFkB,
and selected genetic translocations by fluorescent in situ hybridization (FISH) analysis
(such as Bcl-2 and Bcl-6) with response and PFS in patients receiving initial therapy for
high-risk follicular lymphoma.
VIII. To determine whether immune gene signatures previously identified as prognostic
factors in follicular lymphoma can be applied to paraffin-embedded tissues in ofatumumab and
bendamustine or ofatumumab, bendamustine, and bortezomib treated patients; evaluate microRNA
signatures associated with these gene signatures and outcome.
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.
ARM A:
INDUCTION: Patients receive ofatumumab intravenously (IV) over 2-8 hours on day 1 and
bendamustine hydrochloride IV over 30-60 minutes on days 1 and 2. Treatment repeats every 35
days for up to 6 courses. Patients without disease progression continue on to maintenance
therapy.
MAINTENANCE: Beginning 8 weeks after the start of induction course 6, patients receive
ofatumumab IV over 2-8 hours on day 1. Treatment repeats every 56 days for up to 4 courses.
ARM B:
INDUCTION: Patients receive ofatumumab IV over 2-8 hours on day 1, bendamustine
hydrochloride IV over 30-60 minutes on days 1 and 2, and bortezomib IV over 3-5 seconds on
days 1, 8, 15, and 22. Treatment repeats every 35 days for up to 6 courses. Patients without
disease progression continue on to maintenance therapy.
MAINTENANCE: Beginning 8 weeks after the start of induction course 6, patients receive
ofatumumab IV over 2-8 hours on day 1 and bortezomib IV over 3-5 seconds on days 1, 8, 15,
and 22. Treatment repeats every 56 days for up to 4 courses.
Blood and tumor tissue samples may be collected at baseline and at progression or relapse
for correlative studies. Patients also undergo FDG-PET at baseline and periodically for
restaging.
After completion of study treatment, patients are followed up every 4 months for 2 years and
then every 6 months for up to 10 years.
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Complete response (CR) rate
Up to 10 years
No
Kristie Blum
Principal Investigator
Cancer and Leukemia Group B
United States: Food and Drug Administration
NCI-2011-02625
NCT01286272
April 2011
Name | Location |
---|---|
Washington University School of Medicine | Saint Louis, Missouri 63110 |
Sinai Hospital of Baltimore | Baltimore, Maryland 21225 |
Ingalls Memorial Hospital | Harvey, Illinois 60426 |
North Shore University Hospital | Manhasset, New York 11030 |
Eastern Maine Medical Center | Bangor, Maine 04401 |
University of Oklahoma Health Sciences Center | Oklahoma City, Oklahoma 73104 |
Weill Medical College of Cornell University | New York, New York 10021 |
Long Island Jewish Medical Center | New Hyde Park, New York 11040 |
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center | Columbus, Ohio 43210-1240 |
Iredell Memorial Hospital | Statesville, North Carolina 28677 |
Saint Joseph Mercy Hospital | Ann Arbor, Michigan 48106 |
Altru Cancer Center | Grand Forks, North Dakota 58206 |
Randolph Hospital | Asheboro, North Carolina 27203 |
Spartanburg Regional Medical Center | Spartanburg, South Carolina 29303 |
Queen's Medical Center | Honolulu, Hawaii 96813 |
University of North Carolina | Chapel Hill, North Carolina 27599 |
Kapiolani Medical Center at Pali Momi | Aiea, Hawaii 96701 |
Kapiolani Medical Center for Women and Children | Honolulu, Hawaii 96826 |
Straub Clinic and Hospital | Honolulu, Hawaii 96813 |
Virginia Commonwealth University | Richmond, Virginia |
University of Chicago Comprehensive Cancer Center | Chicago, Illinois 60637-1470 |
Castle Medical Center | Kailua, Hawaii 96734 |
Wake Forest University Health Sciences | Winston-Salem, North Carolina 27157 |
Oncare Hawaii Inc-POB II | Honolulu, Hawaii 96813 |
Evanston CCOP-NorthShore University HealthSystem | Evanston, Illinois 60201 |
Fort Wayne Medical Oncology and Hematology Inc - State Boulevard | Fort Wayne, Indiana 46845 |
Saint Mary's Health Care | Grand Rapids, Michigan 49503 |
Spectrum Health at Butterworth Campus | Grand Rapids, Michigan 49503 |
Minneapolis Veterans Medical Center | Minneapolis, Minnesota 55417 |
Saint Luke's Hospital of Kansas City | Kansas City, Missouri 64111 |
Missouri Baptist Medical Center | Saint Louis, Missouri 63131 |
State University of New York Upstate Medical University | Syracuse, New York 13210 |
Wayne Memorial Hospital | Goldsboro, North Carolina 27534 |
Kinston Medical Specialists PA | Kinston, North Carolina 28501 |
Kettering Medical Center | Kettering, Ohio 45429 |
Saint Charles Hospital | Oregon, Ohio 43616 |
Mercy Cancer Center at Saint Anne Mercy Hospital | Toledo, Ohio 43623 |
University of Illinois | Chicago, Illinois 60612 |
Moores University of California San Diego Cancer Center | LA Jolla, California 92093 |
Michiana Hematology Oncology-PC Westville | Westville, Indiana 46391 |
University of Missouri - Ellis Fischel | Columbia, Missouri 65203 |
Moses Cone Health System-Regional Cancer Center | Greensboro, North Carolina 27403 |
Annie Penn Memorial Hospital | Reidsville, North Carolina 27320 |
Monter Cancer Center | Lake Success, New York 11042 |
Kuakini Medical Center | Honolulu, Hawaii 96817 |
Wilcox Memorial Hospital and Kauai Medical Clinic | Lihue, Hawaii 96766-1099 |
Saint Francis Hospital | Greenville, South Carolina 29601 |
Siouxland Hematology Oncology Associates | Sioux City, Iowa 51101 |
Michiana Hematology Oncology PC-Mishawaka | Mishawaka, Indiana 46545-1470 |
Hematology Oncology Associates of Central New York PC | East Syracuse, New York 13057 |
Franciscan St. Francis Health | Indianapolis, Indiana 46237 |
Cancer and Leukemia Group B | Chicago, Illinois 60606 |
North Shore-LIJ Health System CCOP | Manhasset, New York 11030 |
Oncare Hawaii Inc - Kapiolani Medical Center at Pali Momi | Aiea, Hawaii 96701 |