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

August 16, 2021 updated by: Alliance for Clinical Trials in Oncology

A Phase II Trial of Ofatumumab (CALGB IND #) in Previously Untreated Follicular Non-Hodgkin's Lymphoma (NHL)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

51

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Delaware
      • Lewes, Delaware, United States, 19958
        • Tunnell Cancer Center at Beebe Medical Center
      • Newark, Delaware, United States, 19713
        • CCOP - Christiana Care Health Services
    • Florida
      • Weston, Florida, United States, 33331
        • Cleveland Clinic Florida - Weston
    • Illinois
      • Bloomington, Illinois, United States, 61701
        • Illinois CancerCare - Bloomington
      • Canton, Illinois, United States, 61520
        • Illinois CancerCare - Canton
      • Eureka, Illinois, United States, 61530
        • Illinois CancerCare - Eureka
      • Eureka, Illinois, United States, 61530
        • Eureka Community Hospital
      • Galesburg, Illinois, United States, 61401
        • Galesburg Clinic, PC
      • Macomb, Illinois, United States, 61455
        • Illinois CancerCare - Macomb
      • Normal, Illinois, United States, 61761
        • Bromenn Regional Medical Center
      • Normal, Illinois, United States, 61761
        • Community Cancer Center
      • Normal, Illinois, United States, 61761
        • Illinois CancerCare - Community Cancer Center
      • Ottawa, Illinois, United States, 61350
        • Community Hospital of Ottawa
      • Ottawa, Illinois, United States, 61350
        • Oncology Hematology Associates of Central Illinois, PC - Ottawa
      • Pekin, Illinois, United States, 61554
        • Cancer Treatment Center at Pekin Hospital
      • Pekin, Illinois, United States, 61603
        • Illinois CancerCare - Pekin
      • Peoria, Illinois, United States, 61636
        • Methodist Medical Center of Illinois
      • Peoria, Illinois, United States, 61614
        • Proctor Hospital
      • Peoria, Illinois, United States, 61615
        • CCOP - Illinois Oncology Research Association
      • Peoria, Illinois, United States, 61615
        • Oncology Hematology Associates of Central Illinois, PC - Peoria
      • Peru, Illinois, United States, 61354
        • Illinois CancerCare - Peru
      • Peru, Illinois, United States, 61354
        • Illinois Valley Community Hospital
      • Spring Valley, Illinois, United States, 61362
        • Illinois CancerCare - Spring Valley
    • Iowa
      • Cedar Rapids, Iowa, United States, 52402
        • Iowa Blood and Cancer Care
    • Maryland
      • Elkton, Maryland, United States, 21921
        • Union Hospital of Cecil County
    • Michigan
      • Battle Creek, Michigan, United States, 49017
        • Battle Creek Health System Cancer Care Center
      • Big Rapids, Michigan, United States, 49307
        • Mecosta County Medical Center
      • Grand Rapids, Michigan, United States, 49503
        • Butterworth Hospital at Spectrum Health
      • Grand Rapids, Michigan, United States, 49503
        • CCOP - Grand Rapids
      • Grand Rapids, Michigan, United States, 49503
        • Lacks Cancer Center at Saint Mary's Health Care
      • Muskegon, Michigan, United States, 49444
        • Mercy General Health Partners
      • Reed City, Michigan, United States, 49677
        • Spectrum Health Reed City Hospital
      • Traverse City, Michigan, United States, 49684
        • Munson Medical Center
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
    • New Hampshire
      • Concord, New Hampshire, United States, 03301
        • New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
      • Hooksett, New Hampshire, United States, 03106
        • New Hampshire Oncology - Hematology, PA - Hooksett
      • Laconia, New Hampshire, United States, 03246
        • Lakes Region General Hospital
    • New Jersey
      • Voorhees, New Jersey, United States, 08043
        • Cancer Institute of New Jersey at Cooper - Voorhees
    • New York
      • Lake Success, New York, United States, 11042
        • Monter Cancer Center of the North Shore-LIJ Health System
      • Manhasset, New York, United States, 11030
        • Don Monti Comprehensive Cancer Center at North Shore University Hospital
      • Mount Kisco, New York, United States, 10549-3417
        • Mount Kisco Medical Group, PC
      • New Hyde Park, New York, United States, 11040
        • Long Island Jewish Medical Center
      • New York, New York, United States, 10021
        • New York Weill Cornell Cancer Center at Cornell University
      • Syracuse, New York, United States, 13210
        • SUNY Upstate Medical University Hospital
    • North Carolina
      • Kinston, North Carolina, United States, 28501
        • Kinston Medical Specialists
      • Winston-Salem, North Carolina, United States, 27157-1096
        • Wake Forest University Comprehensive Cancer Center
    • Ohio
      • Columbus, Ohio, United States, 43210-1240
        • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
    • Virginia
      • Richmond, Virginia, United States, 23298-0037
        • Virginia Commonwealth University Massey Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Biological: ofatumumab
Given IV
Experimental: 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.
Biological: ofatumumab
Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (Complete or Partial Response) by Month 12
Time Frame: From baseline to month 12
The primary endpoint of this trial is overall response rate (OR=complete response (CR) or partial response (PR)) to 500 mg or 1000 mg dose of ofatumumab in previously untreated patients with CD20+ follicular NHL. The response outcome is defined as the best response during the 12 months of first-line and extended induction treatment. A CR is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. A PR is defined as at least a 50% decrease in the sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses, with no increase observed in the size of other nodes, liver, or spleen and no new sites of disease should be observed. The ORR (percentage of patients) reported below by arm is the percentage of patients whose best response during the 12 months of treatment was CR or PR.
From baseline to month 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Progression-free Survival Time
Time Frame: From date of study entry until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 4 years
The median progression-free survival (PFS) time for each arm was estimated using the Kaplan-Meier method. PFS was calculated as the time from study entry until progression or death, whichever occurred first. Patients were censored at the time last known alive and progression free. Lymph nodes should be considered abnormal if the long axis is > 1.5 cm, regardless of the short axis. If a lymph node has a long axis of 1.1 to 1.5 cm, it should only be considered abnormal if its short axis is > 1.0. Lymph nodes ≤ 1.0 cm by ≤ 1.0 cm will not be considered as abnormal for relapse or progressive disease. Progression is defined using the 2007 revised response criteria reported by Cheson et al. as follows: Appearance of any new lesion, At least a 50% increase from nadir in the SPD of any previously involved nodes, At least a 50% increase in the longest diameter of any single previously identified node > 1.0 cm in its short axis.
From date of study entry until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alliance for Clinical Trials in Oncology

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Cara A. Rosenbaum, MD, University of Chicago

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2011

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

October 15, 2020

Study Registration Dates

First Submitted

August 26, 2010

First Submitted That Met QC Criteria

August 26, 2010

First Posted (Estimate)

August 27, 2010

Study Record Updates

Last Update Posted (Actual)

August 18, 2021

Last Update Submitted That Met QC Criteria

August 16, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CALGB-50901
  • GSK-CALGB-50901
  • CDR0000683083 (Registry Identifier: NCI Physician Data Query)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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