Non Hodgkin Lymphoma Clinical Trial

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

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.

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Full 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.

View Eligibility Criteria

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 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

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 2

Estimated Enrollment:

135

Study ID:

NCT01286272

Recruitment Status:

Active, not recruiting

Sponsor:

National Cancer Institute (NCI)

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There are 84 Locations for this study

See Locations Near You

UC San Diego Moores Cancer Center
La Jolla California, 92093, United States
Saint Helena Hospital
Saint Helena California, 94574, United States
Middlesex Hospital
Middletown Connecticut, 06457, United States
Mount Sinai Medical Center
Miami Beach Florida, 33140, United States
Pali Momi Medical Center
'Aiea Hawaii, 96701, United States
Queen's Cancer Center - Pearlridge
'Aiea Hawaii, 96701, United States
Hawaii Cancer Care Inc - Waterfront Plaza
Honolulu Hawaii, 96813, United States
Queen's Medical Center
Honolulu Hawaii, 96813, United States
Straub Clinic and Hospital
Honolulu Hawaii, 96813, United States
Hawaii Cancer Care Inc-Liliha
Honolulu Hawaii, 96817, United States
Kuakini Medical Center
Honolulu Hawaii, 96817, United States
Kapiolani Medical Center for Women and Children
Honolulu Hawaii, 96826, United States
Castle Medical Center
Kailua Hawaii, 96734, United States
Wilcox Memorial Hospital and Kauai Medical Clinic
Lihue Hawaii, 96766, United States
Saint Alphonsus Cancer Care Center-Boise
Boise Idaho, 83706, United States
Kootenai Clinic Cancer Services - Post Falls
Post Falls Idaho, 83854, United States
University of Illinois
Chicago Illinois, 60612, United States
University of Chicago Comprehensive Cancer Center
Chicago Illinois, 60637, United States
Weiss Memorial Hospital
Chicago Illinois, 60640, United States
Cancer Care Specialists of Illinois - Decatur
Decatur Illinois, 62526, United States
Decatur Memorial Hospital
Decatur Illinois, 62526, United States
NorthShore University HealthSystem-Evanston Hospital
Evanston Illinois, 60201, United States
Ingalls Memorial Hospital
Harvey Illinois, 60426, United States
Southern Illinois University School of Medicine
Springfield Illinois, 62702, United States
Springfield Clinic
Springfield Illinois, 62702, United States
Memorial Medical Center
Springfield Illinois, 62781, United States
Fort Wayne Medical Oncology and Hematology Inc-Parkview
Fort Wayne Indiana, 46845, United States
Franciscan Health Indianapolis
Indianapolis Indiana, 46237, United States
Memorial Regional Cancer Center Day Road
Mishawaka Indiana, 46545, United States
Michiana Hematology Oncology PC-Mishawaka
Mishawaka Indiana, 46545, United States
Memorial Hospital of South Bend
South Bend Indiana, 46601, United States
Michiana Hematology Oncology PC-Westville
Westville Indiana, 46391, United States
Mercy Hospital
Cedar Rapids Iowa, 52403, United States
Oncology Associates at Mercy Medical Center
Cedar Rapids Iowa, 52403, United States
Siouxland Regional Cancer Center
Sioux City Iowa, 51101, United States
Harold Alfond Center for Cancer Care
Augusta Maine, 04330, United States
Eastern Maine Medical Center
Bangor Maine, 04401, United States
Penobscot Bay Medical Center
Rockport Maine, 04856, United States
Sinai Hospital of Baltimore
Baltimore Maryland, 21215, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor Michigan, 48106, United States
Ascension Saint John Hospital
Detroit Michigan, 48236, United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids Michigan, 49503, United States
Trinity Health Grand Rapids Hospital
Grand Rapids Michigan, 49503, United States
Fairview Ridges Hospital
Burnsville Minnesota, 55337, United States
Fairview Southdale Hospital
Edina Minnesota, 55435, United States
Minnesota Oncology Hematology PA-Maplewood
Maplewood Minnesota, 55109, United States
Saint John's Hospital - Healtheast
Maplewood Minnesota, 55109, United States
Minneapolis VA Medical Center
Minneapolis Minnesota, 55417, United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park Minnesota, 55416, United States
Regions Hospital
Saint Paul Minnesota, 55101, United States
Central Care Cancer Center - Bolivar
Bolivar Missouri, 65613, United States
MU Health - University Hospital/Ellis Fischel Cancer Center
Columbia Missouri, 65212, United States
Saint Luke's Hospital of Kansas City
Kansas City Missouri, 64111, United States
Washington University School of Medicine
Saint Louis Missouri, 63110, United States
Missouri Baptist Medical Center
Saint Louis Missouri, 63131, United States
Mercy Hospital Saint Louis
Saint Louis Missouri, 63141, United States
Mercy Hospital Springfield
Springfield Missouri, 65804, United States
CoxHealth South Hospital
Springfield Missouri, 65807, United States
Billings Clinic Cancer Center
Billings Montana, 59101, United States
Benefis Sletten Cancer Institute
Great Falls Montana, 59405, United States
Nevada Cancer Research Foundation NCORP
Las Vegas Nevada, 89169, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon New Hampshire, 03756, United States
Hematology Oncology Associates of Central New York-East Syracuse
East Syracuse New York, 13057, United States
Northwell Health NCORP
Lake Success New York, 11042, United States
Northwell Health/Center for Advanced Medicine
Lake Success New York, 11042, United States
North Shore University Hospital
Manhasset New York, 11030, United States
Long Island Jewish Medical Center
New Hyde Park New York, 11040, United States
NYP/Weill Cornell Medical Center
New York New York, 10065, United States
State University of New York Upstate Medical University
Syracuse New York, 13210, United States
Randolph Hospital
Asheboro North Carolina, 27203, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill North Carolina, 27599, United States
Wayne Memorial Hospital
Goldsboro North Carolina, 27534, United States
Cone Health Cancer Center
Greensboro North Carolina, 27403, United States
ECU Health Oncology Kinston
Kinston North Carolina, 28501, United States
Annie Penn Memorial Hospital
Reidsville North Carolina, 27320, United States
Iredell Memorial Hospital
Statesville North Carolina, 28677, United States
Wake Forest University Health Sciences
Winston-Salem North Carolina, 27157, United States
Altru Cancer Center
Grand Forks North Dakota, 58201, United States
Ohio State University Comprehensive Cancer Center
Columbus Ohio, 43210, United States
Miami Valley Hospital North
Dayton Ohio, 45415, United States
Kettering Medical Center
Kettering Ohio, 45429, United States
Toledo Clinic Cancer Centers-Maumee
Maumee Ohio, 43537, United States
Saint Charles Hospital
Oregon Ohio, 43616, United States
ProMedica Flower Hospital
Sylvania Ohio, 43560, United States
Mercy Health - Saint Anne Hospital
Toledo Ohio, 43623, United States
Toledo Clinic Cancer Centers-Toledo
Toledo Ohio, 43623, United States
University of Oklahoma Health Sciences Center
Oklahoma City Oklahoma, 73104, United States
Mercy Hospital Oklahoma City
Oklahoma City Oklahoma, 73120, United States
Providence Portland Medical Center
Portland Oregon, 97213, United States
Providence Saint Vincent Medical Center
Portland Oregon, 97225, United States
Guthrie Medical Group PC-Robert Packer Hospital
Sayre Pennsylvania, 18840, United States
Saint Francis Hospital
Greenville South Carolina, 29601, United States
Saint Francis Cancer Center
Greenville South Carolina, 29607, United States
Spartanburg Medical Center
Spartanburg South Carolina, 29303, United States
Virginia Commonwealth University/Massey Cancer Center
Richmond Virginia, 23298, United States
West Virginia University Healthcare
Morgantown West Virginia, 26506, United States

How clear is this clinincal trial information?

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 2

Estimated Enrollment:

135

Study ID:

NCT01286272

Recruitment Status:

Active, not recruiting

Sponsor:


National Cancer Institute (NCI)

How clear is this clinincal trial information?

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