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

Basic Trial Information

Trial Description

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.

Further Study Information

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.

Eligibility 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

Trial Contact Information

Trial Lead Organizations/Sponsors

Cancer and Leukemia Group B

Cara A. Rosenbaum

Principal Investigator

U.S.A.
Delaware
	Lewes
	Tunnell Cancer Center at Beebe Medical Center
		Stephen Scott Grubbs	Ph: 302-733-6227
	Newark
	Helen F. Graham Cancer Center at Christiana Hospital
		Stephen Scott Grubbs	Ph: 302-733-6227
District of Columbia
	Washington
	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
		Bruce David Cheson	Ph: 202-444-0381
Florida
	Weston
	Cleveland Clinic Florida - Weston
		James E Hoffman	Ph: 954-659-5705
Illinois
	Bloomington
	Illinois CancerCare - Bloomington
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Canton
	Illinois CancerCare - Canton
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Chicago
	University of Chicago Cancer Research Center
		Cara A. Rosenbaum	Ph: 773-834-7424
	Eureka
	Eureka Community Hospital
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Illinois CancerCare - Eureka
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Galesburg
	Galesburg Clinic, PC
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Macomb
	Illinois CancerCare - Macomb
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Normal
	BroMenn Regional Medical Center
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Community Cancer Center
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Illinois CancerCare - Community Cancer Center
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Ottawa
	Community Hospital of Ottawa
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Illinois CancerCare - Ottawa
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Pekin
	Cancer Treatment Center at Pekin Hospital
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Illinois CancerCare - Pekin
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Peoria
	CCOP - Illinois Oncology Research Association
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Illinois CancerCare - Peoria
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Methodist Medical Center of Illinois
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Proctor Hospital
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Peru
	Illinois CancerCare - Princeton
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Illinois Valley Community Hospital
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Spring Valley
	Illinois CancerCare - Spring Valley
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
Iowa
	Cedar Rapids
	Iowa Blood and Cancer Care
		David O. Zenk	Ph: 319-297-2900
			Email: cetscheidt@pcofiowa.com
Maryland
	Elkton MD
	Union Hospital of Cecil County
		Stephen Scott Grubbs	Ph: 302-733-6227
Michigan
	Battle Creek
	Battle Creek Health System Cancer Care Center
		Gilbert D Padula	Ph: 616-685-5225
	Big Rapids
	Mecosta County Medical Center
		Gilbert D Padula	Ph: 616-685-5225
	Grand Rapids
	Butterworth Hospital at Spectrum Health
		Gilbert D Padula	Ph: 616-685-5225
	CCOP - Grand Rapids
		Gilbert D Padula	Ph: 616-685-5225
	Lacks Cancer Center at Saint Mary's Health Care
		Gilbert D Padula	Ph: 616-685-5225
	Muskegon
	Mercy General Health Partners
		Gilbert D Padula	Ph: 616-685-5225
	Reed City
	Spectrum Health Reed City Hospital
		Gilbert D Padula	Ph: 616-685-5225
	Traverse City
	Munson Medical Center
		Gilbert D Padula	Ph: 616-685-5225
Missouri
	Saint Louis
	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
		Nancy L. Bartlett	Ph: 800-600-3606
			Email: info@siteman.wustl.edu
New Hampshire
	Concord
	New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
		Frederick M. Briccetti	Ph: 800-339-6484
	Hooksett
	New Hampshire Oncology - Hematology, PA - Hooksett
		Frederick M. Briccetti	Ph: 800-339-6484
	Laconia
	Lakes Region General Hospital
		Frederick M. Briccetti	Ph: 800-339-6484
New Jersey
	Camden
	Cancer Institute of New Jersey at Cooper University Hospital - Camden
		Stephen Scott Grubbs	Ph: 302-733-6227
New York
	Lake Success
	Monter Cancer Center of the North Shore-LIJ Health System
		Dilip V. Patel	Ph: 516-562-3467
	Manhasset
	Don Monti Comprehensive Cancer Center at North Shore University Hospital
		Dilip V. Patel	Ph: 516-562-3467
	Mount Kisco
	Northern Westchester Hospital
		Jonathan S Goldberg	Ph: 914-666-1366
			Email: skloiber@nwhc.net
	New Hyde Park
	Long Island Jewish Medical Center
		Dilip V. Patel	Ph: 516-562-3467
	New York
	New York Weill Cornell Cancer Center at Cornell University
		Peter Martin	Ph: 212-746-1848
	Syracuse
	SUNY Upstate Medical University Hospital
		Teresa C. Gentile	Ph: 315-464-5476
North Carolina
	Kinston
	Kinston Medical Specialists
		Peter R. Watson	Ph: 252-559-2200
	Winston-Salem
	Wake Forest University Comprehensive Cancer Center
		Denise Angelique Levitan	Ph: 336-713-6771
Ohio
	Columbus
	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
		Beth A Christian	Ph: 866-627-7616
			Email: osu@emergingmed.com
Virginia
	Richmond
	Virginia Commonwealth University Massey Cancer Center
		Beata Holkova	Ph: 804-628-1939

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01190449
Information obtained from ClinicalTrials.gov on February 18, 2013