Ofatumumab and Bendamustine Hydrochloride with or without Bortezomib in Treating Patients with Untreated Follicular Non-Hodgkin Lymphoma

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IIBiomarker/Laboratory analysis, Treatment18 and overCALGB 50904
NCI-2011-02625, CDR0000694298, 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

Granulocytes >= 1,000/uL

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

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

Platelet count >= 75,000/uL

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

Creatinine =< 2.0 mg/dL

Bilirubin =< 2 x ULN

No prior cytotoxic chemotherapy, radiotherapy, immunotherapy, or radioimmunotherapy

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

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)

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

National Cancer Institute

  • National Cancer Institute
Kristie A. Blum, Principal Investigator

Trial Sites

U.S.A.

California
La Jolla

UC San Diego Moores Cancer Center

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

Erin Gourley Reid
Principal Investigator

Saint Helena

Saint Helena Hospital

Gregory B. Smith
Ph: 707-967-3698

Gregory B. Smith
Principal Investigator

Connecticut
Middletown

Middlesex Hospital

Susanna Hong
Ph: 860-358-2058

Susanna Hong
Principal Investigator

Florida
Miami Beach

Mount Sinai Medical Center

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

Michael A. Schwartz
Principal Investigator

Idaho
Post Falls

Kootenai Cancer Center

Benjamin T. Marchello
Ph: 800-648-6274

Benjamin T. Marchello
Principal Investigator

Illinois
Evanston

NorthShore University HealthSystem-Evanston Hospital

Lynne S. Kaminer
Ph: 847-570-2109

Lynne S. Kaminer
Principal Investigator

Indiana
Mishawaka

Memorial Regional Cancer Center Day Road

Thomas Joseph Reid
Ph: 800-284-7370

Thomas Joseph Reid
Principal Investigator

South Bend

Memorial Hospital of South Bend

Thomas Joseph Reid
Ph: 800-284-7370

Thomas Joseph Reid
Principal Investigator

Iowa
Cedar Rapids

Mercy Hospital

Deborah Weil Wilbur
Ph: 319-363-2690

Deborah Weil Wilbur
Principal Investigator

Oncology Associates at Mercy Medical Center

Deborah Weil Wilbur
Ph: 319-363-2690

Deborah Weil Wilbur
Principal Investigator

Sioux City

Siouxland Regional Cancer Center

Donald B. Wender
Ph: 712-252-0088

Donald B. Wender
Principal Investigator

Maine
Augusta

Harold Alfond Center for Cancer Care

Thomas H. Openshaw
Ph: 207-973-4274

Thomas H. Openshaw
Principal Investigator

Bangor

Eastern Maine Medical Center

Thomas H. Openshaw
Ph: 207-973-4274

Thomas H. Openshaw
Principal Investigator

Rockport

Penobscot Bay Medical Center

Thomas H. Openshaw
Ph: 207-973-4274

Thomas H. Openshaw
Principal Investigator

Maryland
Baltimore

Sinai Hospital of Baltimore

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

Roberto F. Martinez
Principal Investigator

Michigan
Ann Arbor

Saint Joseph Mercy Hospital

Christopher M. Reynolds
Ph: 734-712-4673

Christopher M. Reynolds
Principal Investigator

Detroit

Saint John Hospital and Medical Center

Christopher M. Reynolds
Ph: 734-712-4673

Christopher M. Reynolds
Principal Investigator

Grand Rapids

Mercy Health Saint Mary's

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

Gilbert D.A. Padula
Principal Investigator

Spectrum Health at Butterworth Campus

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

Gilbert D.A. Padula
Principal Investigator

Minnesota
Edina

Fairview-Southdale Hospital

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

Patrick James Flynn
Principal Investigator

Minneapolis

Minneapolis Veterans Medical Center

Sharon Davis Luikart
Ph: 612-467-2800

Sharon Davis Luikart
Principal Investigator

Saint Paul

Regions Hospital

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

Patrick James Flynn
Principal Investigator

Missouri
Columbia

University of Missouri - Ellis Fischel

Donald C. Doll
Ph: 573-882-7440

Donald C. Doll
Principal Investigator

Saint Louis

Mercy Hospital Saint Louis

Jay W. Carlson
Ph: 800-821-7532

Jay W. Carlson
Principal Investigator

Washington University School of Medicine

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

Nancy L. Bartlett
Principal Investigator

Springfield

CoxHealth South Hospital

Jay W. Carlson
Ph: 800-821-7532

Jay W. Carlson
Principal Investigator

Mercy Hospital Springfield

Jay W. Carlson
Ph: 800-821-7532

Jay W. Carlson
Principal Investigator

Montana
Billings

Billings Clinic Cancer Center

Benjamin T. Marchello
Ph: 800-648-6274

Benjamin T. Marchello
Principal Investigator

Nevada
Las Vegas

Nevada Cancer Research Foundation CCOP

John Allan Ellerton
Ph: 702-384-0013

John Allan Ellerton
Principal Investigator

New Hampshire
Lebanon

Dartmouth Hitchcock Medical Center

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

Frederick Lansigan
Principal Investigator

New York
East Syracuse

Hematology Oncology Associates of Central New York-East Syracuse

Jeffrey J. Kirshner
Ph: 315-472-7504

Jeffrey J. Kirshner
Principal Investigator

Syracuse

State University of New York Upstate Medical University

Dorothy C. Pan
Ph: 315-464-5476

Dorothy C. Pan
Principal Investigator

North Carolina
Asheboro

Randolph Hospital

James Mitchell Granfortuna
Ph: 336-832-0821

James Mitchell Granfortuna
Principal Investigator

Chapel Hill

University of North Carolina at Chapel Hill

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

Steven I. Park
Principal Investigator

Goldsboro

Wayne Memorial Hospital

James N. Atkins
Ph: 919-580-0000

James N. Atkins
Principal Investigator

Greensboro

Cone Health Cancer Center

James Mitchell Granfortuna
Ph: 336-832-0821

James Mitchell Granfortuna
Principal Investigator

Kinston

Kinston Medical Specialists PA

Peter Robins Watson
Ph: 252-559-2200

Peter Robins Watson
Principal Investigator

Reidsville

Annie Penn Memorial Hospital

James Mitchell Granfortuna
Ph: 336-832-0821

James Mitchell Granfortuna
Principal Investigator

Statesville

Iredell Memorial Hospital

Ruby Ann Grimm
Ph: 704-873-5661

Ruby Ann Grimm
Principal Investigator

Winston-Salem

Wake Forest University Health Sciences

David Duane Hurd
Ph: 336-713-6771

David Duane Hurd
Principal Investigator

North Dakota
Grand Forks

Altru Cancer Center

Grant Richard Seeger
Ph: 701-780-6520

Grant Richard Seeger
Principal Investigator

Ohio
Columbus

Ohio State University Comprehensive Cancer Center

Kristie A. Blum
Ph: 614-293-3196

Kristie A. Blum
Principal Investigator

Maumee

Toledo Clinic Cancer Centers-Maumee

Rex B. Mowat
Ph: 800-444-3561

Rex B. Mowat
Principal Investigator

Oregon

Saint Charles Hospital

Rex B. Mowat
Ph: 800-444-3561

Rex B. Mowat
Principal Investigator

Toledo

Mercy Saint Anne Hospital

Rex B. Mowat
Ph: 800-444-3561

Rex B. Mowat
Principal Investigator

Toledo Clinic Cancer Centers-Toledo

Rex B. Mowat
Ph: 800-444-3561

Rex B. Mowat
Principal Investigator

Oklahoma
Oklahoma City

Mercy Hospital Oklahoma City

Vikki A. Canfield
Ph: 405-751-4343

Vikki A. Canfield
Principal Investigator

University of Oklahoma Health Sciences Center

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

Mohamad Cherry
Principal Investigator

Oregon
Portland

Providence Portland Medical Center

Keith S. Lanier
Ph: 503-215-6412

Keith S. Lanier
Principal Investigator

Providence Saint Vincent Medical Center

Keith S. Lanier
Ph: 503-215-6412

Keith S. Lanier
Principal Investigator

South Carolina
Spartanburg

Spartanburg Medical Center

Charles E. Bowers
Ph: 800-486-5941

Charles E. Bowers
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01286272

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.