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Ofatumumab and Bendamustine Hydrochloride With or Without Bortezomib in Treating Patients With Untreated Follicular Non-Hodgkin Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01286272
First received: January 27, 2011
Last updated: November 10, 2016
Last verified: August 2016
  Purpose
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.

Condition Intervention Phase
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
Drug: Bendamustine Hydrochloride
Drug: Bortezomib
Radiation: Fludeoxyglucose F-18
Other: Laboratory Biomarker Analysis
Biological: Ofatumumab
Procedure: Positron Emission Tomography with Radiolabeled Targeting Agent
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Ofatumumab and Bendamustine vs. Ofatumumab, Bortezomib (NSC #681239) and Bendamustine in Patients With Untreated Follicular Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • CR rate [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Grade 3 or higher toxicities assessed according to NCI Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
    The toxicity profile of the two arms will be summarized using frequency tables. The chi-squared test will be conducted to compare the toxicity rate of grade 3 or higher between the two arms.

  • Immunohistochemical (IHC) markers [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The IHC markers will be correlated with response (using the two-sample t-test) and PFS (using the Cox regression method) data. No multiple testing adjustment will be applied because of the small sample size.

  • PFS [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Kaplan-Meier curves of PFS and overall survival (OS) will be generated for the two arms. The p-values of the log-rank test will be calculated to compare PFS and OS between the two arms.

  • Pre-treatment single nucleotide polymorphisms (SNP) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The PFS will be compared among the three genotype groups of each SNP using the log-rank tests. A maxtype test will be used by taking the maximum value of the log-rank tests under dominant, recessive, and proportional hazard model. The critical value (or p-value) of the max test will be obtained by a permutation method. No multiple testing adjustment may be applied because of the small sample size.

  • Predictive value of FDG-PET [ Time Frame: Up to 36-38 weeks (6-8 weeks after course 6, day 1 after last course of induction chemotherapy) ] [ Designated as safety issue: No ]
    The ratio will be correlated with response (using the two-sample t-test) and PFS (using the Cox regression method) data.


Estimated Enrollment: 130
Study Start Date: April 2011
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (ofatumumab, bendamustine hydrochloride)

INDUCTION: Patients receive ofatumumab 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.

Drug: Bendamustine Hydrochloride
Given IV
Other Names:
  • Bendamustin Hydrochloride
  • Cytostasan Hydrochloride
  • Levact
  • Ribomustin
  • SyB L-0501
  • Treanda
Radiation: Fludeoxyglucose F-18
Undergo FDG-PET
Other Names:
  • 18FDG
  • FDG
  • fludeoxyglucose F 18
  • Fludeoxyglucose F18
  • Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
  • Fluorodeoxyglucose F18
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Ofatumumab
Given IV
Other Names:
  • Arzerra
  • GSK1841157
  • HuMax-CD20
  • HuMax-CD20, 2F2
Procedure: Positron Emission Tomography with Radiolabeled Targeting Agent
Undergo FDG-PET
Other Name: Positron Emission Tomography with Radiolabeled Targeting Agents
Experimental: Arm B (ofatumumab, bendamustine hydrochloride, bortezomib)

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 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.

Drug: Bendamustine Hydrochloride
Given IV
Other Names:
  • Bendamustin Hydrochloride
  • Cytostasan Hydrochloride
  • Levact
  • Ribomustin
  • SyB L-0501
  • Treanda
Drug: Bortezomib
Given IV or SC
Other Names:
  • [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid
  • LDP 341
  • MLN341
  • PS-341
  • PS341
  • Velcade
Radiation: Fludeoxyglucose F-18
Undergo FDG-PET
Other Names:
  • 18FDG
  • FDG
  • fludeoxyglucose F 18
  • Fludeoxyglucose F18
  • Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
  • Fluorodeoxyglucose F18
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Ofatumumab
Given IV
Other Names:
  • Arzerra
  • GSK1841157
  • HuMax-CD20
  • HuMax-CD20, 2F2
Procedure: Positron Emission Tomography with Radiolabeled Targeting Agent
Undergo FDG-PET
Other Name: Positron Emission Tomography with Radiolabeled Targeting Agents

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01286272

  Hide Study Locations
Locations
United States, California
UC San Diego Moores Cancer Center
La Jolla, California, United States, 92093
Saint Helena Hospital
Saint Helena, California, United States, 94574
United States, Connecticut
Middlesex Hospital
Middletown, Connecticut, United States, 06457
United States, Florida
Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
United States, Idaho
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, United States, 83706
Kootenai Cancer Center
Post Falls, Idaho, United States, 83854
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
Cancer Care Center of Decatur
Decatur, Illinois, United States, 62526
Decatur Memorial Hospital
Decatur, Illinois, United States, 62526
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, United States, 60201
Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
Southern Illinois University School of Medicine
Springfield, Illinois, United States, 62702
Springfield Clinic
Springfield, Illinois, United States, 62703
Memorial Medical Center
Springfield, Illinois, United States, 62781
United States, Indiana
Memorial Regional Cancer Center Day Road
Mishawaka, Indiana, United States, 46544
Michiana Hematology Oncology PC-Mishawaka
Mishawaka, Indiana, United States, 46545
Memorial Hospital of South Bend
South Bend, Indiana, United States, 46601
Michiana Hematology Oncology PC-Westville
Westville, Indiana, United States, 46391
United States, Iowa
Mercy Hospital
Cedar Rapids, Iowa, United States, 52403
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, United States, 52403
Siouxland Regional Cancer Center
Sioux City, Iowa, United States, 51101
United States, Maine
Harold Alfond Center for Cancer Care
Augusta, Maine, United States, 04330
Eastern Maine Medical Center
Bangor, Maine, United States, 04401
Penobscot Bay Medical Center
Rockport, Maine, United States, 04856
United States, Maryland
Sinai Hospital of Baltimore
Baltimore, Maryland, United States, 21215
United States, Michigan
Saint Joseph Mercy Hospital
Ann Arbor, Michigan, United States, 48106-0995
Saint John Hospital and Medical Center
Detroit, Michigan, United States, 48236
Mercy Health Saint Mary's
Grand Rapids, Michigan, United States, 49503
Spectrum Health at Butterworth Campus
Grand Rapids, Michigan, United States, 49503
United States, Minnesota
Fairview Ridges Hospital
Burnsville, Minnesota, United States, 55337
Fairview-Southdale Hospital
Edina, Minnesota, United States, 55435
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, United States, 55109
Saint John's Hospital - Healtheast
Maplewood, Minnesota, United States, 55109
Minneapolis Veterans Medical Center
Minneapolis, Minnesota, United States, 55417
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, United States, 55416
Regions Hospital
Saint Paul, Minnesota, United States, 55101
United States, Missouri
Central Care Cancer Center-Carrie J Babb Cancer Center
Bolivar, Missouri, United States, 65613
University of Missouri - Ellis Fischel
Columbia, Missouri, United States, 65212
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, United States, 64111
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Missouri Baptist Medical Center
Saint Louis, Missouri, United States, 63131
Mercy Hospital Saint Louis
Saint Louis, Missouri, United States, 63141
Mercy Hospital Springfield
Springfield, Missouri, United States, 65804
CoxHealth South Hospital
Springfield, Missouri, United States, 65807
United States, Montana
Billings Clinic Cancer Center
Billings, Montana, United States, 59101
Benefis Healthcare- Sletten Cancer Institute
Great Falls, Montana, United States, 59405
United States, Nevada
Nevada Cancer Research Foundation CCOP
Las Vegas, Nevada, United States, 89106
United States, New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New York
Hematology Oncology Associates of Central New York-East Syracuse
East Syracuse, New York, United States, 13057
Northwell Health NCORP
Lake Success, New York, United States, 11042
Weill Medical College of Cornell University
New York, New York, United States, 10065
State University of New York Upstate Medical University
Syracuse, New York, United States, 13210
United States, North Carolina
Randolph Hospital
Asheboro, North Carolina, United States, 27203
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States, 27599
Wayne Memorial Hospital
Goldsboro, North Carolina, United States, 27534
Cone Health Cancer Center
Greensboro, North Carolina, United States, 27403
Kinston Medical Specialists PA
Kinston, North Carolina, United States, 28501
Annie Penn Memorial Hospital
Reidsville, North Carolina, United States, 27320
Iredell Memorial Hospital
Statesville, North Carolina, United States, 28677
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, North Dakota
Altru Cancer Center
Grand Forks, North Dakota, United States, 58201
United States, Ohio
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
Toledo Clinic Cancer Centers-Maumee
Maumee, Ohio, United States, 43537
Saint Charles Hospital
Oregon, Ohio, United States, 43616
Flower Hospital
Sylvania, Ohio, United States, 43560
Mercy Saint Anne Hospital
Toledo, Ohio, United States, 43623
Toledo Clinic Cancer Centers-Toledo
Toledo, Ohio, United States, 43623
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
Mercy Hospital Oklahoma City
Oklahoma City, Oklahoma, United States, 73120
United States, Oregon
Providence Portland Medical Center
Portland, Oregon, United States, 97213
Providence Saint Vincent Medical Center
Portland, Oregon, United States, 97225
United States, Pennsylvania
Guthrie Medical Group PC-Robert Packer Hospital
Sayre, Pennsylvania, United States, 18840
United States, South Carolina
Saint Francis Hospital
Greenville, South Carolina, United States, 29601
Saint Francis Cancer Center
Greenville, South Carolina, United States, 29607
Spartanburg Medical Center
Spartanburg, South Carolina, United States, 29303
United States, Virginia
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, United States, 23298
United States, West Virginia
West Virginia University Healthcare
Morgantown, West Virginia, United States, 26506
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Kristie Blum Alliance for Clinical Trials in Oncology
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01286272     History of Changes
Other Study ID Numbers: NCI-2011-02625  NCI-2011-02625  CDR0000694298  CALGB-50904  CALGB 50904  CALGB-50904  U10CA180821  U10CA031946 
Study First Received: January 27, 2011
Last Updated: November 10, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Bortezomib
Bendamustine Hydrochloride
Fluorodeoxyglucose F18
Antibodies, Monoclonal
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Radiopharmaceuticals
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 02, 2016