A Phase II Trial of Ofatumumab in Subjects With Waldenstrom's Macroglobulinemia

April 28, 2017 updated by: GlaxoSmithKline
Given the tolerability and efficacy of ofatumumab in follicular lymphoma and Chronic Lymphocytic Leukemia, and the need to improve therapy for patients with WM utilizing a non-myelosuppressive agent this phase II trial of ofatumumab is being initiated in patients with Waldenstrom's Macroglobulinemia (WM).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

37

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
    • California
      • Los Angeles, California, United States, 90095-6984
        • GSK Investigational Site
      • Stanford, California, United States, 94305
        • GSK Investigational Site
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • GSK Investigational Site
    • New York
      • Buffalo, New York, United States, 14263
        • GSK Investigational Site
      • New York, New York, United States, 10021
        • GSK Investigational Site
    • Ohio
      • Columbus, Ohio, United States, 43210-1228
        • GSK Investigational Site
    • Texas
      • San Antonio, Texas, United States, 78229
        • GSK Investigational Site

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

Inclusion Criteria:

  • Confirmed and active Waldenstrom's Macroglobulinemia requiring treatment.
  • Ambulatory and capable of all selfcare. Up and about more than 50% of waking hours.
  • Adequate organ function.
  • Detectable CD20 positive of the tumor cells.
  • Measurable disease as defined by a monoclonal IgM paraprotein level greater than 1000 mg/dL.

Exclusion Criteria:

  • Treatment of WM within the past 28 days.
  • Treatment with rituximab or alemtuzamab within the past 3 months.
  • Certain heart problems, chronic or current active infection not controlled with oral antibiotics, other current cancer or within last 5 years.
  • Current participation in another interventional clinical study.
  • Lactating or pregnant women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception.
  • Active cerebrovascular disease.

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: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ofatumumab
Ofatumumab is a fully human antibody, targeting a unique epitope on the CD20 molecule expressed on human B cells.
Biological: Ofatumumab
Ofatumumab is a fully human antibody, targeting a unique epitope on the CD20 molecule expressed on human B cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Overall Response (OR) for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator
Time Frame: Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment
OR (based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM) included Complete Response (CR), Partial Response (PR), or a Minor Response (MR). CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline.
Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment
Number of Participants With OR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator
Time Frame: Baseline and up to Study Week 16
OR (based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM) included Complete Response (CR), Partial Response (PR), or a Minor Response (MR). CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline.
Baseline and up to Study Week 16

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With CR, PR, and MR for Cycle 1 (Including the Redosing Cycle), as Assessed by the Investigator
Time Frame: Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment
Response criteria were based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM. CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline.
Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment
Number of Participants With CR, PR, and MR for Cycle 1 (Excluding the Redosing Cycle), as Assessed by the Investigator
Time Frame: Baseline and up to Study Week 16
Response criteria were based on the Consensus Panel recommendations from the 2nd and 3rd International Workshop on WM. CR: Complete disappearance of serum monoclonal (SM) Immunoglobulin (Ig) E (IgE), measured centrally; resolution of adenopathy/organomegaly upon physical exam and computerized tomography (CT) scan; lymph nodes =<1.5 centimeters; absence of malignant cell by bone marrow histologic examination. PR: a >=50% reduction from baseline in the SM IgM concentration. MR: >=25%, but a <50% reduction of SM IgM from baseline.
Baseline and up to Study Week 16
Number of Participants With IgM Flare for Cycle 1 Response (Including the Redosing Cycle)
Time Frame: Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment
IgM is a basic antibody that is produced by B cells. It is the first antibody to appear in response to initial exposure to antigen. IgM flare is defined as an IgM level that increases by >25% from baseline (BL) and is associated with a response to treatment. Avoidance of IgM flare indicates the lack of an increase in IgM of >25% from BL.
Baseline and up to 27 months from the first dose of Cycle 1 (Study Day 1), and before Cycle 2 treatment
Duration of Response for All Responders (CR, PR, MR), as Assessed by the Investigator
Time Frame: From baseline up to approximately 5 years
Duration of response is defined as the time from the initial response to relapse/disease progression (DP) or death. DP for CR is defined as the reappearance of the IgM protein, new signs/symptoms attributable to WM, evidence of active disease or recurrence of bone marrow involvement by lymphoplasmacytic cells, or the appearance of any new lymph node >=1.5 centimeters on any axis. Progression for PR/MR is either a >=25% increase in IgM from the lowest attained response value or progression of lymphadenopathy, organomegaly, cytopenias, or other clinically significant signs/symptoms caused by WM.
From baseline up to approximately 5 years
Progression-free Survival
Time Frame: From baseline up to approximately 5 years
Time to disease progression is defined as the time from baseline to disease progression or death.
From baseline up to approximately 5 years
Time to Response for Responders
Time Frame: From baseline up to approximately 5 years
Time to response is defined as the time from baseline to the first response date.
From baseline up to approximately 5 years
Overall Survival
Time Frame: From baseline up to approximately 5 years
Overall survival is defined as the time from baseline until death due to any cause.
From baseline up to approximately 5 years
Clearance of Ofatumumab
Time Frame: From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7
Clearance (CL) is defined as the volume of plasma that is cleared of drug per unit of time. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7
Volume of Distribution at Steady State of Ofatumumab
Time Frame: From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7
Volume of distribution at steady state (Vss) is defined as the apparent volume of distribution of the drug in the body at steady state. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7
Half-life of Ofatumumab
Time Frame: From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7
Half-life (t½) is defined as the time required for the concentration of the drug in plasma to decrease to one-half of its current value. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7
Cmax and Ctrough of Ofatumumab
Time Frame: From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7
Cmax is defined as the maximum observed drug concentration after administration, and Ctrough is defined as the drug concentration observed prior to the start of the next dose. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7
AUC(0-tau) and AUC(0-inf) of Ofatumumab
Time Frame: From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7
AUC(0-tau) is the area under the drug concentration-time curve over the dosing interval (one week). AUC(0-inf) is the area under the drug concentration-time curve from time zero extrapolated to infinite time. Blood samples for the quantification of ofatumumab were collected during each cycle and for up to 6 months after the end of each cycle.
From the first dose (Cycle 1 Day 1) up to 6 months after the end of the last cycle of treatment; blood collected on each dosing day, weekly up to Week 8, and every 4 weeks up to Week 24/Month 7
Number of Participants With at Least One Confirmed Positive Post-ofatumumab HAHA Result
Time Frame: From baseline up to approximately 5 years
All human-antihuman antibody (HAHA) samples were first tested in a screening assay to identify potential HAHA positives. Next, samples that tested positive in the screening assay were further tested in the confirmation assay to determine the specificity of the signal to ofatumumab. Confirmed positive samples were reported as positive.
From baseline up to approximately 5 years
Change From Baseline in Blood Counts (CD4+, CD19+, CD50) at Month 3 After Treatment
Time Frame: Baseline and Month 3
CD4+ and CD19+ are two key flow cytometry parameters, and total hemolytic complement (CD50) is a complement parameter. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Baseline and Month 3
Number of Participants With the Indicated SAEs Related to Study Drug
Time Frame: From baseline up to approximately 5 years
An SAE is any event occurring at any dose that results in any of the following: death, a life-threatening adverse drug experience (ADE; at immediate risk of death from the experience as it occurred), inpatient hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, or a congenital anomaly/birth defect. Medical events that may not result in death, be life threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the Investigator's medical judgement.
From baseline up to approximately 5 years
Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug
Time Frame: From baseline up to approximately 5 years
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The Investigator assessed whether the AE was possibly or probably related to study drug.
From baseline up to approximately 5 years
Number of Participants With the Indicated AEs Leading to Permanent Discontinuation of Study Drug and Withdrawal From Study
Time Frame: From baseline up to approximately 5 years
Certain AEs led to permanent discontinuation of study drug and hence resulted in their withdrawal from the study.
From baseline up to approximately 5 years
Number of Participants With the Indicated >=Grade 3 AEs
Time Frame: From baseline up to approximately 5 years
AEs were graded using the Common Toxicity Criteria for AEs from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE.
From baseline up to approximately 5 years
Number of Participants With the Indicated Infusion-related >=Grade 3 AE
Time Frame: From baseline up to approximately 5 years
Infusion-related AEs are the AEs that resulted from administration of study drug through infusion. AEs were graded using the Common Toxicity Criteria for AEs from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0 = No AE or within normal limits; 1 = Mild AE; 2 = Moderate AE; 3 = Severe and undesirable AE; 4 = Life-threatening or disabling AE; 5 = Death related to AE.
From baseline up to approximately 5 years

Collaborators and Investigators

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

Sponsor

GlaxoSmithKline

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

March 1, 2009

Primary Completion (Actual)

June 1, 2011

Study Completion (Actual)

February 1, 2014

Study Registration Dates

First Submitted

December 18, 2008

First Submitted That Met QC Criteria

December 18, 2008

First Posted (Estimate)

December 19, 2008

Study Record Updates

Last Update Posted (Actual)

May 30, 2017

Last Update Submitted That Met QC Criteria

April 28, 2017

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 110921

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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