Ofatumumab in Treating Patients With Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma

NCT ID: NCT01190449

Last Updated: 2021-08-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2020-10-15

Brief Summary

RATIONALE: Monoclonal antibodies, such as ofatumumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them.

PURPOSE: This randomized phase II trial is studying ofatumumab to see how well it works in treating patients with previously untreated stage II, stage III, or stage IV follicular non-Hodgkin lymphoma.

Detailed Description

OBJECTIVES:

Primary

• To determine the response rate in patients with previously untreated CD20-positive bulky stage II, or stage III or IV follicular non-Hodgkin lymphoma (NHL) treated with a lower- or high-dose of ofatumumab.

Secondary

• To determine the progression-free survival (PFS) of patients treated with these regimens.
• To determine the toxicity profile of these regimens in these patients.
• To establish whether the therapeutic effect of single-agent ofatumumab is sufficiently promising to warrant evaluation in subsequent randomized, ofatumumab-based, biologic doublet trials.
• To evaluate the two ofatumumab doses by independent comparison of response, PFS, and toxicity to a historical control in previously untreated patients with follicular NHL.
• To prospectively validate the FLIPI2 prognostic index in low- and intermediate-risk patients and compare to low- and intermediate-risk stratified patients by standard FLIPI scoring to determine a more reliable indicator of response and PFS.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive high-dose ofatumumab IV over 2-8 hours on days 1, 8, 15, and 22 and then once monthly in months 3-9.
• Arm II: Patients receive a lower dose of ofatumumab IV over 2-8 hours on days 1, 8, 15, and 22 and then once monthly in months 3-9.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients may undergo blood and bone marrow sample collection for correlative studies.

After completion of study therapy, patients are followed up every 4 months for 2 years and then every 6 months for 8 years.

Conditions

Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

Patients receive high-dose ofatumumab IV over 2-8 hours on days 1, 8, 15, and 22 and then once monthly in months 3-9.

Group Type: EXPERIMENTAL

ofatumumab

Intervention Type: BIOLOGICAL

Given IV

Arm II

Patients receive a lower dose of ofatumumab IV over 2-8 hours on days 1, 8, 15, and 22 and then once monthly in months 3-9.

Group Type: EXPERIMENTAL

ofatumumab

Intervention Type: BIOLOGICAL

Given IV

Interventions

ofatumumab

Given IV

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed follicular non-Hodgkin lymphoma (NHL) meeting 1 of the following criteria:

• Bulky (i.e., single mass ≥ 7cm in any uni-dimensional measurement) stage II disease
• Stage III or IV disease
• WHO grade 1, 2, or 3a disease
• Bone marrow biopsies allowed provided they are submitted in conjunction with nodal biopsies

• No fine-needle aspirates for diagnosis
• Tumor tissue must express the CD20-positive antigen by flow cytometry or IHC
• At least 1 site of measurable disease that is > 1 cm in diameter in ≥ 1 dimension present either on physical exam or imaging studies

• Non-measurable disease alone not allowed, including the following:

• Bone lesions (lesions if present should be noted)
• Ascites
• Pleural/pericardial effusion
• Lymphangitis cutis/pulmonis
• Bone marrow (involvement by NHL should be noted)
• Low- or intermediate-risk disease by the Follicular Lymphoma International Prognostic Index (FLIPI)

• FLIPI score meeting 1 or 2 of the following risk factors:

• Age > 60 years
• Involvement of > 4 nodal sites
• Stage III-IV disease
• Hemoglobin < 12.0 g/dL
• LDH normal
• Risk determined by the following:

• Low Risk: 0-1 of the above risk factors
• Intermediate Risk: 2 risk factors
• Poor Risk: ≥ 3 risk factors
• No known CNS involvement

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• ANC ≥ 1,000/μL
• Platelet count ≥ 75,000/μL
• Creatinine clearance ≥ 30 mL/min
• Bilirubin ≤ 2 times upper limit of normal (unless secondary to Gilbert syndrome or hepatic involvement of NHL)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment
• Patients with HIV infection allowed provided the following criteria are met:

• No evidence of coinfection with hepatitis B or C
• CD4+ cell count ≥ 400/mm³
• No evidence of resistant strains of HIV
• HIV viral load < 10,000 copies HIV RNA/mL if not on anti-HIV therapy OR HIV viral load < 50 copies if on anti-HIV therapy
• No history of AIDS-defining conditions
• No evidence of active hepatitis B (HBV) or C (HCV) infection (i.e., no positive serology for anti-HBc or anti-HCV antibodies)

• HBV seropositivity allowed (HBsAg+) provided they are closely monitored for evidence of active HBV infection by HBV DNA testing
• After completing treatment, HBsAg + patients must be monitored by HBV DNA testing every 2 months for 6 months post-treatment, while continuing lamivudine (required)

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or immunotherapy (e.g., monoclonal antibody-based therapy) for NHL

• Prior involved-field radiation therapy allowed
• More than 2 weeks since prior corticosteroids except for maintenance therapy for a non-malignant disease

• No concurrent dexamethasone or other steroids as antiemetics
• No live virus vaccination within 6 weeks prior to study entry
• No concurrent zidvoudine or stavudine

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cara A. Rosenbaum, MD

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

Locations

Tunnell Cancer Center at Beebe Medical Center

Lewes, Delaware, United States

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Cleveland Clinic Florida - Weston

Weston, Florida, United States

Illinois CancerCare - Bloomington

Bloomington, Illinois, United States

Illinois CancerCare - Canton

Canton, Illinois, United States

Eureka Community Hospital

Eureka, Illinois, United States

Illinois CancerCare - Eureka

Eureka, Illinois, United States

Galesburg Clinic, PC

Galesburg, Illinois, United States

Illinois CancerCare - Macomb

Macomb, Illinois, United States

BroMenn Regional Medical Center

Normal, Illinois, United States

Community Cancer Center

Normal, Illinois, United States

Illinois CancerCare - Community Cancer Center

Normal, Illinois, United States

Community Hospital of Ottawa

Ottawa, Illinois, United States

Oncology Hematology Associates of Central Illinois, PC - Ottawa

Ottawa, Illinois, United States

Cancer Treatment Center at Pekin Hospital

Pekin, Illinois, United States

Illinois CancerCare - Pekin

Pekin, Illinois, United States

Proctor Hospital

Peoria, Illinois, United States

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

Oncology Hematology Associates of Central Illinois, PC - Peoria

Peoria, Illinois, United States

Methodist Medical Center of Illinois

Peoria, Illinois, United States

Illinois CancerCare - Peru

Peru, Illinois, United States

Illinois Valley Community Hospital

Peru, Illinois, United States

Illinois CancerCare - Spring Valley

Spring Valley, Illinois, United States

Iowa Blood and Cancer Care

Cedar Rapids, Iowa, United States

Union Hospital of Cecil County

Elkton, Maryland, United States

Battle Creek Health System Cancer Care Center

Battle Creek, Michigan, United States

Mecosta County Medical Center

Big Rapids, Michigan, United States

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, United States

CCOP - Grand Rapids

Grand Rapids, Michigan, United States

Lacks Cancer Center at Saint Mary's Health Care

Grand Rapids, Michigan, United States

Mercy General Health Partners

Muskegon, Michigan, United States

Spectrum Health Reed City Hospital

Reed City, Michigan, United States

Munson Medical Center

Traverse City, Michigan, United States

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care

Concord, New Hampshire, United States

New Hampshire Oncology - Hematology, PA - Hooksett

Hooksett, New Hampshire, United States

Lakes Region General Hospital

Laconia, New Hampshire, United States

Cancer Institute of New Jersey at Cooper - Voorhees

Voorhees Township, New Jersey, United States

Monter Cancer Center of the North Shore-LIJ Health System

Lake Success, New York, United States

Don Monti Comprehensive Cancer Center at North Shore University Hospital

Manhasset, New York, United States

Mount Kisco Medical Group, PC

Mount Kisco, New York, United States

Long Island Jewish Medical Center

New Hyde Park, New York, United States

New York Weill Cornell Cancer Center at Cornell University

New York, New York, United States

SUNY Upstate Medical University Hospital

Syracuse, New York, United States

Kinston Medical Specialists

Kinston, North Carolina, United States

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

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

Columbus, Ohio, United States

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, United States

Countries

United States

References

Rutherford SC, Yin J, Pederson L, Perez Burbano G, LaPlant B, Shadman M, Li H, LeBlanc ML, Kenkre VP, Hong F, Blum KA, Dockter T, Martin P, Jung SH, Grant B, Rosenbaum C, Ujjani C, Barr PM, Unger JM, Cheson BD, Bartlett NL, Kahl B, Friedberg JW, Mandrekar SJ, Leonard JP. Relevance of Bone Marrow Biopsies for Response Assessment in US National Cancer Institute National Clinical Trials Network Follicular Lymphoma Clinical Trials. J Clin Oncol. 2023 Jan 10;41(2):336-342. doi: 10.1200/JCO.21.02301. Epub 2022 Jul 5.

Reference Type: DERIVED

PMID: 35787017 (View on PubMed)

Other Identifiers

CALGB-50901

Identifier Type: -

Identifier Source: secondary_id

GSK-CALGB-50901

Identifier Type: -

Identifier Source: secondary_id

CDR0000683083

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-50901

Identifier Type: -

Identifier Source: org_study_id