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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01190449
Recruitment Status : Active, not recruiting
First Posted : August 27, 2010
Results First Posted : July 26, 2018
Last Update Posted : July 10, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Tracking Information
First Submitted Date  ICMJE August 26, 2010
First Posted Date  ICMJE August 27, 2010
Results First Submitted Date  ICMJE April 16, 2018
Results First Posted Date  ICMJE July 26, 2018
Last Update Posted Date July 10, 2019
Actual Study Start Date  ICMJE August 2011
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 26, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 26, 2010)
Overall response (complete or partial response)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 26, 2018)
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 26, 2010)
  • Progression-free survival
  • Tolerability
  • Comparison of two ofatumumab doses efficacy with historical controls
  • Comparison of two ofatumumab doses toxicity with historical controls
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ofatumumab in Treating Patients With Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma
Official Title  ICMJE A Phase II Trial of Ofatumumab (CALGB IND #) in Previously Untreated Follicular Non-Hodgkin's Lymphoma (NHL)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma
Intervention  ICMJE Biological: ofatumumab
Given IV
Study Arms  ICMJE
  • 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.
    Intervention: Biological: ofatumumab
  • 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.
    Intervention: Biological: ofatumumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 11, 2017)
51
Original Estimated Enrollment  ICMJE
 (submitted: August 26, 2010)
100
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01190449
Other Study ID Numbers  ICMJE CALGB-50901
CALGB-50901
GSK-CALGB-50901
CDR0000683083 ( Registry Identifier: NCI Physician Data Query )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alliance for Clinical Trials in Oncology
Study Sponsor  ICMJE Alliance for Clinical Trials in Oncology
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Cara A. Rosenbaum, MD University of Chicago
PRS Account Alliance for Clinical Trials in Oncology
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP