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

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIBiomarker/Laboratory analysis, TreatmentActive18 and overNCINCI-2011-02625
CDR0000694298, CALGB 50904, U10CA180821, U10CA031946, NCT01286272

Trial Description

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 or by stopping them from dividing. 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.

Further Study Information

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 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 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 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.

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.

Eligibility 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 10-14 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 ribonucleic acid (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

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

    Kristie Blum, Principal Investigator

    Trial Sites

    U.S.A.

    California
    La Jolla

    Rebecca and John Moores UCSD Cancer Center

    Erin G Reid
    Ph: 858-822-5354
    Email: cancercto@ucsd.edu

    Saint Helena

    Saint Helena Hospital

    Gregory B Smith
    Ph: 707-967-3698

    Connecticut
    Middletown

    Middlesex Hospital Cancer Center

    Susanna Hong
    Ph: 860-358-2058

    Florida
    Miami Beach

    CCOP - Mount Sinai Medical Center

    Michael Schwartz
    Ph: 305-674-2625
    Email: info@msccop.com

    Idaho
    Post Falls

    Kootenai Cancer Center - Post Falls

    Benjamin Thomas Marchello
    Ph: 800-648-6274

    Illinois
    Evanston

    CCOP - Evanston

    Lynne S. Kaminer
    Ph: 847-570-2109

    Harvey

    Ingalls Cancer Care Center at Ingalls Memorial Hospital

    Mark F. Kozloff
    Ph: 708-915-4673
    Email: clinicaltrials@ingalls.org

    Indiana
    Mishawaka

    Memorial Regional Cancer Center Day Road

    Thomas Joseph Reid
    Ph: 800-284-7370

    Michiana Hematology-Oncology, PC - Mishawaka

    Rafat H. Ansari
    Ph: 574-234-5123

    South Bend

    Memorial Hospital of South Bend

    Thomas Joseph Reid
    Ph: 800-284-7370

    Westville

    Michiana Hematology Oncology-PC Westville

    Rafat H. Ansari
    Ph: 574-234-5123

    Iowa
    Cedar Rapids

    Cedar Rapids Oncology Associates

    Deborah W Wilbur
    Ph: 319-363-2690

    Mercy Regional Cancer Center at Mercy Medical Center

    Deborah W Wilbur
    Ph: 319-363-2690

    Sioux City

    Siouxland Hematology-Oncology Associates, LLP

    Donald Bruce Wender
    Ph: 712-252-0088

    Maine
    Augusta

    Harold Alfond Center for Cancer Care

    Thomas Henry Openshaw
    Ph: 207-973-4274

    Bangor

    CancerCare of Maine at Eastern Maine Medical Center

    Thomas Henry Openshaw
    Ph: 207-973-4274

    Rockport

    Penobscot Bay Medical Center Cancer Care Center

    Thomas Henry Openshaw
    Ph: 207-973-4274

    Maryland
    Baltimore

    Alvin and Lois Lapidus Cancer Institute at Sinai Hospital

    Roberto F Martinez
    Ph: 410-601-6120
    Email: pridgely@lifebridgehealth.org

    Michigan
    Ann Arbor

    Saint Joseph Mercy Cancer Center

    Christopher M Reynolds
    Ph: 734-712-4673

    Detroit

    Van Elslander Cancer Center at St. John Hospital and Medical Center

    Christopher M Reynolds
    Ph: 734-712-4673

    Grand Rapids

    Butterworth Hospital at Spectrum Health

    Gilbert D Padula
    Ph: 616-685-5225
    Email: connie.szczepanek@grcop.org

    Lacks Cancer Center at Saint Mary's Health Care

    Gilbert D Padula
    Ph: 616-685-5225
    Email: connie.szczepanek@grcop.org

    Minnesota
    Edina

    Fairview Southdale Hospital

    Patrick J. Flynn
    Ph: 952-993-1517
    Email: MMCCOP@parknicollet.com

    Minneapolis

    Veterans Affairs Medical Center - Minneapolis

    Sharon D Luikart
    Ph: 612-467-2800

    Missouri
    Bolivar

    Central Care Cancer Center at Carrie J. Babb Cancer Center

    Jay W Carlson
    Ph: 800-821-7532

    Columbia

    Ellis Fischel Cancer Center at University of Missouri - Columbia

    Donald C Doll
    Ph: 573-882-7440

    Saint Louis

    David C. Pratt Cancer Center at St. John's Mercy

    Jay W Carlson
    Ph: 800-821-7532

    Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

    Nancy L. Bartlett
    Ph: 800-600-3606
    Email: info@siteman.wustl.edu

    Springfield

    Hulston Cancer Center at Cox Medical Center South

    Jay W Carlson
    Ph: 800-821-7532

    St. John's Regional Health Center

    Jay W Carlson
    Ph: 800-821-7532

    Montana
    Billings

    Billings Clinic Cancer Center - 801 N 29th Street

    Benjamin Thomas Marchello
    Ph: 800-648-6274

    Nevada
    Las Vegas

    CCOP - Nevada Cancer Research Foundation

    John Allan Ellerton
    Ph: 702-384-0013

    New Hampshire
    Lebanon

    Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center

    Frederick Lansigan
    Ph: 800-639-6918
    Email: cancer.research.nurse@dartmouth.edu

    New York
    East Syracuse

    CCOP - Hematology-Oncology Associates of Central New York

    Jeffrey J. Kirshner
    Ph: 315-472-7504

    Syracuse

    SUNY Upstate Medical University Hospital

    Dorothy C Pan
    Ph: 315-464-5476

    North Carolina
    Asheboro

    Randolph Hospital

    James M Granfortuna
    Ph: 336-832-0821

    Chapel Hill

    Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

    Steven I Park
    Ph: 877-668-0683
    Email: cancerclinicaltrials@med.unc.edu

    Goldsboro

    Wayne Memorial Hospital, Incorporated

    James N. Atkins
    Ph: 919-580-0000

    Greensboro

    Moses Cone Regional Cancer Center at Wesley Long Community Hospital

    James M Granfortuna
    Ph: 336-832-0821

    Kinston

    Kinston Medical Specialists

    Peter R. Watson
    Ph: 252-559-2200

    Reidsville

    Annie Penn Cancer Center

    James M Granfortuna
    Ph: 336-832-0821

    Statesville

    Iredell Memorial Hospital

    Ruby A. Grimm
    Ph: 704-873-5661

    Winston-Salem

    Wake Forest University Comprehensive Cancer Center

    David Duane Hurd
    Ph: 336-713-6771

    North Dakota
    Grand Forks

    Altru Cancer Center at Altru Hospital

    Grant R Seeger
    Ph: 701-780-6520

    Ohio
    Columbus

    Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

    Kristie A. Blum
    Ph: 614-293-3196

    Maumee

    Northwest Ohio Oncology Center

    Rex B Mowat
    Ph: 800-444-3561

    Oregon

    St. Charles Mercy Hospital

    Rex B Mowat
    Ph: 800-444-3561

    Toledo

    St. Anne Mercy Hospital

    Rex B Mowat
    Ph: 800-444-3561

    Toledo Clinic, Incorporated - Main Clinic

    Rex B Mowat
    Ph: 800-444-3561

    Oklahoma
    Oklahoma City

    Mercy Health Center

    Vikki Ann Canfield
    Ph: 405-751-4343

    Stephenson Cancer Center at the University of Oklahoma

    Mohamad Cherry
    Ph: 405-271-4272
    Email: julie-traylor@ouhsc.edu

    South Carolina
    Spartanburg

    Gibbs Regional Cancer Center at Spartanburg Regional Medical Center

    Charles E Bowers
    Ph: 800-486-5941

    Link to the current ClinicalTrials.gov record.
    NLM Identifier NCT01286272
    ClinicalTrials.gov processed this data on May 20, 2015

    Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.