Ofatumumab and Bendamustine Hydrochloride With or Without Bortezomib in Treating Patients With Untreated Follicular Non-Hodgkin Lymphoma
Conditions
Grade 3a Follicular Lymphoma - Stage III Grade 1 Follicular Lymphoma - Stage III Grade 2 Follicular Lymphoma - Stage III Grade 3 Follicular Lymphoma - Stage IV Grade 1 Follicular Lymphoma - Stage IV Grade 2 Follicular Lymphoma - Stage IV Grade 3 Follicular Lymphoma
Conditions: official terms
Lymphoma - Lymphoma, Follicular
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Bendamustine Hydrochloride Type: Drug
Name: Bortezomib Type: Drug
Name: Fludeoxyglucose F-18 Type: Radiation
Name: Laboratory Biomarker Analysis Type: Other
Name: Ofatumumab Type: Biological
Name: Positron Emission Tomography with Radiolabeled Targeting Agent Type: Procedure
Overall Status
Recruiting
Summary
This randomized phase II trial studies how well ofatumumab and bendamustine hydrochloride with or without bortezomib works in treating patients with untreated follicular non-Hodgkin lymphoma. Monoclonal antibodies, such as ofatumumab, may block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Bortezomib may also stop the growth of cancer cells by blocking blood flow to the tumor. It is not yet known whether ofatumumab and bendamustine hydrochloride are more effective with bortezomib in treating patients with follicular non-Hodgkin lymphoma.
Detailed Description
PRIMARY OBJECTIVES:

I. To determine the complete response (CR) rate in newly diagnosed, untreated follicular lymphoma patients receiving 6 cycles of ofatumumab-bendamustine (bendamustine hydrochloride) (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 semi-quantitative 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 cluster of differentiation (CD)-68, B-cell chronic lymphocytic leukemia (CLL)/lymphoma (bcl)-2, marker of proliferation Ki-67 (Ki-67), forkhead box P3 (FOXP3), activated cytotoxic T-cells, lymphoma-associated macrophages (LAM), melanoma associated antigen (mutated) 1 (MUM1), CD10, nuclear v-rel avian reticuloendotheliosis viral oncogene homolog A (p65) and v-rel avian reticuloendotheliosis viral oncogene homolog C (cREL) subunits of nuclear factor of kappa light polypeptide gene enhancer in B-cells (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 micro-ribonucleic acid (RNA) signatures associated with these gene signatures and outcome.

OUTLINE: 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 or subcutaneously (SC) 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 or SC on days 1, 8, 15, and 22. Treatment repeats every 56 days for up to 4 courses.

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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Histologically confirmed follicular non-Hodgkin lymphoma, World Health Organization (WHO) classification grade 1, 2, or 3a (> 15 centroblasts per high-power field with centrocytes present)

- Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies

- Fine-needle aspirates are not acceptable

- Failure to submit pathology within 60 days of patient registration will be considered a major protocol violation

- Patients must have at least one of the following indicators of poor risk disease:

- >= 3 risk factors by the Follicular Lymphoma International Prognostic Index, or 2 risk factors by the Follicular Lymphoma International Prognostic Index and at least one bulky mass or lymph node > 6 cm in size

- Follicular Lymphoma International Prognostic Index (FLIPI score):

- Age > 60 years

- Involvement of > 4 nodal sites

- Stage III-IV disease

- Hemoglobin < 12.0 g/dL

- Lactate dehydrogenase (LDH) > upper limit of normal (ULN)

- 0-1 of the above risk factors: low risk

- 2 risk factors: intermediate risk

- >= 3 risk factors: poor risk

- No prior cytotoxic chemotherapy, radiotherapy, immunotherapy, or radioimmunotherapy

- No corticosteroids are permitted, except for maintenance therapy for a non-malignant disease or to prevent treatment-related ofatumumab reactions (maintenance therapy dose must not exceed 20 mg/day prednisone or equivalent)

- Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable; any tumor mass > 1 cm is acceptable; lesions that are considered non-measurable include the following:

- Bone lesions

- Leptomeningeal disease

- Ascites

- Pleural/pericardial effusion

- Inflammatory breast disease

- Lymphangitis cutis/pulmonis

- Bone marrow involvement (involvement by non-Hodgkin lymphoma should be noted)

- Patients must have no known central nervous system (CNS) involvement by lymphoma

- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Patients must be non-pregnant and non-nursing; pregnant or nursing patients may not be enrolled; women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to registration; in addition, women and men of childbearing potential must commit to use an effective form of contraception throughout their participation in this study; appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives (Norplant), or double barrier method (diaphragm plus condom)

- Patients with human immunodeficiency virus (HIV) infection are eligible; patients with HIV infection must meet the following: no evidence of co-infection with hepatitis B or C; CD4+ count > 400/ul; no evidence of resistant strains of HIV; on anti-HIV therapy with an HIV viral load < 50 copies HIV RNA/mL; no history of acquired immunodeficiency syndrome (AIDS)-defining conditions; no zidovudine or stavudine are allowed owing to overlapping toxicity with chemotherapy

- Patients must have no evidence of active hepatitis B or C infection (i.e., no positive serology for anti-hepatitis B core [HBc] or anti-hepatitis C virus [HCV] antibodies); hepatitis B virus (HBV) seropositive patients (hepatitis B surface antigen [HBsAg] +) are eligible if HBV deoxyribonucleic acid (DNA) is undetectable at baseline and they are closely monitored for evidence of active HBV infection by HBV DNA testing at each treatment cycle; after completing treatment, HBsAg + patients must be monitored by HBV DNA testing every 2 months for 6 months post-treatment, while continuing lamivudine

- Granulocytes >= 1,000/uL

- Platelet count >= 75,000/uL

- Creatinine =< 2.0 mg/dL

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limits of normal (ULN)

- Bilirubin =< 2 x ULN
Locations
UC San Diego Moores Cancer Center
La Jolla, California, United States
Status: Recruiting
Contact: Erin G. Reid - 858-822-5354 - cancercto@ucsd.edu
Saint Helena Hospital
Saint Helena, California, United States
Status: Recruiting
Contact: Gregory B. Smith - 707-967-3698
Middlesex Hospital
Middletown, Connecticut, United States
Status: Recruiting
Contact: Susanna Hong - 860-358-2058
Mount Sinai Medical Center
Miami Beach, Florida, United States
Status: Recruiting
Contact: Michael A. Schwartz - 305-674-2625 - info@msccop.com
Oncare Hawaii Inc-Pali Momi
Aiea, Hawaii, United States
Status: Withdrawn
Pali Momi Medical Center
Aiea, Hawaii, United States
Status: Withdrawn
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, United States
Status: Withdrawn
Kuakini Medical Center
Honolulu, Hawaii, United States
Status: Withdrawn
Oncare Hawaii Inc-POB II
Honolulu, Hawaii, United States
Status: Withdrawn
OnCare Hawaii-Liliha
Honolulu, Hawaii, United States
Status: Withdrawn
Queen's Medical Center
Honolulu, Hawaii, United States
Status: Withdrawn
Straub Clinic and Hospital
Honolulu, Hawaii, United States
Status: Withdrawn
Castle Medical Center
Kailua, Hawaii, United States
Status: Withdrawn
Wilcox Memorial Hospital and Kauai Medical Clinic
Lihue, Hawaii, United States
Status: Withdrawn
Kootenai Cancer Center
Post Falls, Idaho, United States
Status: Recruiting
Contact: Benjamin T. Marchello - 800-648-6274
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Status: Active, not recruiting
University of Illinois
Chicago, Illinois, United States
Status: Withdrawn
Weiss Memorial Hospital
Chicago, Illinois, United States
Status: Withdrawn
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, United States
Status: Recruiting
Contact: Lynne S. Kaminer - 847-570-2109
Ingalls Memorial Hospital
Harvey, Illinois, United States
Status: Recruiting
Contact: Mark F. Kozloff - 708-915-4673 - clinicaltrials@ingalls.org
Fort Wayne Medical Oncology and Hematology Inc-Parkview
Fort Wayne, Indiana, United States
Status: Withdrawn
Franciscan Saint Francis Health-Indianapolis
Indianapolis, Indiana, United States
Status: Withdrawn
Memorial Regional Cancer Center Day Road
Mishawaka, Indiana, United States
Status: Recruiting
Contact: Thomas J. Reid - 800-284-7370
Michiana Hematology Oncology PC-Mishawaka
Mishawaka, Indiana, United States
Status: Terminated
Memorial Hospital of South Bend
South Bend, Indiana, United States
Status: Recruiting
Contact: Thomas J. Reid - 800-284-7370
Michiana Hematology Oncology PC-Westville
Westville, Indiana, United States
Status: Terminated
Mercy Hospital
Cedar Rapids, Iowa, United States
Status: Active, not recruiting
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, United States
Status: Active, not recruiting
Siouxland Regional Cancer Center
Sioux City, Iowa, United States
Status: Recruiting
Contact: Donald B. Wender - 712-252-0088
Harold Alfond Center for Cancer Care
Augusta, Maine, United States
Status: Recruiting
Contact: Thomas H. Openshaw - 207-973-4274
Eastern Maine Medical Center
Bangor, Maine, United States
Status: Recruiting
Contact: Thomas H. Openshaw - 207-973-4274
Penobscot Bay Medical Center
Rockport, Maine, United States
Status: Recruiting
Contact: Thomas H. Openshaw - 207-973-4274
Sinai Hospital of Baltimore
Baltimore, Maryland, United States
Status: Recruiting
Contact: Roberto F. Martinez - 410-601-6120 - pridgely@lifebridgehealth.org
Saint Joseph Mercy Hospital
Ann Arbor, Michigan, United States
Status: Recruiting
Contact: Christopher M. Reynolds - 734-712-4673
Saint John Hospital and Medical Center
Detroit, Michigan, United States
Status: Recruiting
Contact: Christopher M. Reynolds - 734-712-4673
Mercy Health Saint Mary's
Grand Rapids, Michigan, United States
Status: Recruiting
Contact: Gilbert D. Padula - 616-685-5225 - connie.szczepanek@grcop.org
Spectrum Health at Butterworth Campus
Grand Rapids, Michigan, United States
Status: Recruiting
Contact: Gilbert D. Padula - 616-685-5225 - connie.szczepanek@grcop.org
Fairview-Southdale Hospital
Edina, Minnesota, United States
Status: Recruiting
Contact: Patrick J. Flynn - 952-993-1517 - MMCCOP@parknicollet.com
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, United States
Status: Recruiting
Contact: Patrick J. Flynn - 952-993-1517 - MMCCOP@parknicollet.com
Minneapolis Veterans Medical Center
Minneapolis, Minnesota, United States
Status: Recruiting
Contact: Sharon D. Luikart - 612-467-2800
Regions Hospital
Saint Paul, Minnesota, United States
Status: Recruiting
Contact: Patrick J. Flynn - 952-993-1517 - MMCCOP@parknicollet.com
Central Care Cancer Center-Carrie J Babb Cancer Center
Bolivar, Missouri, United States
Status: Active, not recruiting
University of Missouri - Ellis Fischel
Columbia, Missouri, United States
Status: Recruiting
Contact: Donald C. Doll - 573-882-7440
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, United States
Status: Active, not recruiting
Mercy Hospital Saint Louis
Saint Louis, Missouri, United States
Status: Recruiting
Contact: Jay W. Carlson - 800-821-7532
Missouri Baptist Medical Center
Saint Louis, Missouri, United States
Status: Active, not recruiting
Washington University School of Medicine
Saint Louis, Missouri, United States
Status: Recruiting
Contact: Nancy L. Bartlett - 800-600-3606 - info@siteman.wustl.edu
CoxHealth South Hospital
Springfield, Missouri, United States
Status: Recruiting
Contact: Jay W. Carlson - 800-821-7532
Mercy Hospital Springfield
Springfield, Missouri, United States
Status: Recruiting
Contact: Jay W. Carlson - 800-821-7532
Billings Clinic Cancer Center
Billings, Montana, United States
Status: Recruiting
Contact: Benjamin T. Marchello - 800-648-6274
Nevada Cancer Research Foundation CCOP
Las Vegas, Nevada, United States
Status: Recruiting
Contact: John A. Ellerton - 702-384-0013
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States
Status: Recruiting
Contact: Frederick Lansigan - 800-639-6918 - cancer.research.nurse@dartmouth.edu
Hematology Oncology Associates of Central New York-East Syracuse
East Syracuse, New York, United States
Status: Recruiting
Contact: Jeffrey J. Kirshner - 315-472-7504
North Shore University Hospital
Manhasset, New York, United States
Status: Withdrawn
North Shore-LIJ Health System NCORP
Manhasset, New York, United States
Status: Terminated
Long Island Jewish Medical Center
New Hyde Park, New York, United States
Status: Withdrawn
North Shore-LIJ Health System/Center for Advanced Medicine
New Hyde Park, New York, United States
Status: Withdrawn
Weill Medical College of Cornell University
New York, New York, United States
Status: Active, not recruiting
State University of New York Upstate Medical University
Syracuse, New York, United States
Status: Recruiting
Contact: Dorothy C. Pan - 315-464-5476
Randolph Hospital
Asheboro, North Carolina, United States
Status: Recruiting
Contact: James M. Granfortuna - 336-832-0821
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Status: Recruiting
Contact: Steven I. Park - 877-668-0683 - cancerclinicaltrials@med.unc.edu
Wayne Memorial Hospital
Goldsboro, North Carolina, United States
Status: Recruiting
Contact: James N. Atkins - 919-580-0000
Cone Health Cancer Center
Greensboro, North Carolina, United States
Status: Recruiting
Contact: James M. Granfortuna - 336-832-0821
Kinston Medical Specialists PA
Kinston, North Carolina, United States
Status: Recruiting
Contact: Peter R. Watson - 252-559-2200
Annie Penn Memorial Hospital
Reidsville, North Carolina, United States
Status: Recruiting
Contact: James M. Granfortuna - 336-832-0821
Iredell Memorial Hospital
Statesville, North Carolina, United States
Status: Recruiting
Contact: Ruby A. Grimm - 704-873-5661
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Status: Recruiting
Contact: David D. Hurd - 336-713-6771
Altru Cancer Center
Grand Forks, North Dakota, United States
Status: Recruiting
Contact: Grant R. Seeger - 701-780-6520
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Status: Recruiting
Contact: Kristie A. Blum - 614-293-3196
Samaritan North Health Center
Dayton, Ohio, United States
Status: Withdrawn
Kettering Medical Center
Kettering, Ohio, United States
Status: Withdrawn
Toledo Clinic Cancer Centers-Maumee
Maumee, Ohio, United States
Status: Recruiting
Contact: Rex B. Mowat - 800-444-3561
Saint Charles Hospital
Oregon, Ohio, United States
Status: Recruiting
Contact: Rex B. Mowat - 800-444-3561
Flower Hospital
Sylvania, Ohio, United States
Status: Terminated
Mercy Saint Anne Hospital
Toledo, Ohio, United States
Status: Recruiting
Contact: Rex B. Mowat - 800-444-3561
Toledo Clinic Cancer Centers-Toledo
Toledo, Ohio, United States
Status: Recruiting
Contact: Rex B. Mowat - 800-444-3561
Mercy Hospital Oklahoma City
Oklahoma City, Oklahoma, United States
Status: Recruiting
Contact: Vikki A. Canfield - 405-751-4343
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Status: Recruiting
Contact: Mohamad Cherry - 405-271-4272 - julie-traylor@ouhsc.edu
Providence Portland Medical Center
Portland, Oregon, United States
Status: Recruiting
Contact: Keith S. Lanier - 503-215-6412
Providence Saint Vincent Medical Center
Portland, Oregon, United States
Status: Recruiting
Contact: Keith S. Lanier - 503-215-6412
Saint Francis Hospital
Greenville, South Carolina, United States
Status: Active, not recruiting
Spartanburg Medical Center
Spartanburg, South Carolina, United States
Status: Recruiting
Contact: Charles E. Bowers - 800-486-5941
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, United States
Status: Active, not recruiting
West Virginia University Healthcare
Morgantown, West Virginia, United States
Status: Active, not recruiting
Start Date
April 2011
Sponsors
National Cancer Institute (NCI)
Source
National Cancer Institute (NCI)
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page