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Clinical Trials (PDQ®)

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

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

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 BlumPrincipal 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
Hawaii
  Aiea
 Kapiolani Medical Center at Pali Momi
 Jeffrey L. Berenberg Ph: 808-586-2979
 Jeffrey L. Berenberg Ph: 808-586-2979
  Honolulu
 Kapiolani Medical Center for Women and Children
 Jeffrey L. Berenberg Ph: 808-586-2979
 Kuakini Medical Center
 Jeffrey L. Berenberg Ph: 808-586-2979
 OnCare Hawaii, Incorporated - Kuakini
 Jeffrey L. Berenberg Ph: 808-586-2979
 OnCare Hawaii, Incorporated - Lusitana
 Jeffrey L. Berenberg Ph: 808-586-2979
 Queen's Cancer Institute at Queen's Medical Center
 Jeffrey L. Berenberg Ph: 808-586-2979
 Straub Clinic and Hospital, Incorporated
 Jeffrey L. Berenberg Ph: 808-586-2979
  Lihue
 Kauai Medical Clinic
 Jeffrey L. Berenberg Ph: 808-586-2979
Idaho
  Post Falls
 Kootenai Cancer Center - Post Falls
 Benjamin Thomas Marchello Ph: 800-648-6274
Illinois
  Chicago
 University of Illinois Cancer Center
 David J. Peace Ph: 312-355-3046
  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
  Indianapolis
 St. Francis Hospital Cancer Care Services
 Stephen E Rubenstein Ph: 317-851-2555
  Mishawaka
 Michiana Hematology-Oncology, PC - Mishawaka
 Rafat H. Ansari Ph: 574-234-5123
  Westville
 Michiana Hematology Oncology-PC Westville
 Rafat H. Ansari Ph: 574-234-5123
Iowa
  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
 Lacks Cancer Center at Saint Mary's Health Care
 Gilbert D Padula Ph: 616-685-5225
Minnesota
  Minneapolis
 Veterans Affairs Medical Center - Minneapolis
 Sharon D Luikart Ph: 612-467-2800
Missouri
  Columbia
 Ellis Fischel Cancer Center at University of Missouri - Columbia
 Carl E. Freter Ph: 573-882-7440
  Kansas City
 Saint Luke's Hospital
 Rakesh Gaur Ph: 913-948-5588
  Email: aroland@kccop.org
  Saint Louis
 David C. Pratt Cancer Center at St. John's Mercy
 Jay W Carlson Ph: 800-821-7532
  Email: sherrijr@iora.org
 Missouri Baptist Cancer Center
 Alan Philip Lyss Ph: 800-392-0936
 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
  Email: sherrijr@iora.org
 St. John's Regional Health Center
 Jay W Carlson Ph: 800-821-7532
  Email: sherrijr@iora.org
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 York
  East Syracuse
 CCOP - Hematology-Oncology Associates of Central New York
 Jeffrey J. Kirshner Ph: 315-472-7504
  New York
 New York Weill Cornell Cancer Center at Cornell University
 Peter Martin Ph: 212-746-1848
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: 866-627-7616
  Email: osu@emergingmed.com
 Kristie A. Blum Ph: 614-293-3196
  Dayton
 Samaritan North Cancer Care Center
 Howard M. Gross Ph: 937-775-1350
  Kettering
 Charles F. Kettering Memorial Hospital
 Howard M. Gross Ph: 937-775-1350
  Oregon
 St. Charles Mercy Hospital
 Rex B Mowat Ph: 517-265-0116
  Toledo
 St. Anne Mercy Hospital
 Rex B Mowat Ph: 517-265-0116
 Toledo Clinic, Incorporated - Main Clinic
 Rex B Mowat Ph: 517-265-0116
Oklahoma
  Oklahoma City
 Cancer Care Associates - Mercy Campus
 Vikki Ann Canfield Ph: 405-271-4272
  Email: julie-traylor@ouhsc.edu
 Oklahoma University Cancer Institute
 Mohamad Cherry Ph: 405-271-4272
  Email: julie-traylor@ouhsc.edu
Oregon
  Portland
 Providence Cancer Center at Providence Portland Medical Center
 Alison K Conlin Ph: 503-215-6412
Virginia
  Richmond
 Virginia Commonwealth University Massey Cancer Center
 Beata Holkova Ph: 804-628-1939
West Virginia
  Morgantown
 Mary Babb Randolph Cancer Center at West Virginia University Hospitals
 Michael D Craig Ph: 304-293-2745
  Email: sfilburn@hsc.wvu.edu

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01286272
ClinicalTrials.gov processed this data on October 15, 2014

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.

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