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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00811733
First received: December 18, 2008
Last updated: March 26, 2015
Last verified: February 2015
  Purpose

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).


Condition Intervention Phase
Waldenstrom Macroglobulinaemia
Biological: Ofatumumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Ofatumumab in Subjects With Waldenstrom's Macroglobulinemia

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Duration of Response for All Responders (CR, PR, MR), as Assessed by the Investigator [ Time Frame: From baseline up to approximately 5 years ] [ Designated as safety issue: No ]
    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.

  • Progression-free Survival [ Time Frame: From baseline up to approximately 5 years ] [ Designated as safety issue: No ]
    Time to disease progression is defined as the time from baseline to disease progression or death.

  • Time to Response for Responders [ Time Frame: From baseline up to approximately 5 years ] [ Designated as safety issue: No ]
    Time to response is defined as the time from baseline to the first response date.

  • Overall Survival [ Time Frame: From baseline up to approximately 5 years ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from baseline until death due to any cause.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With at Least One Confirmed Positive Post-ofatumumab HAHA Result [ Time Frame: From baseline up to approximately 5 years ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Blood Counts (CD4+, CD19+, CD50) at Month 3 After Treatment [ Time Frame: Baseline and Month 3 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With the Indicated SAEs Related to Study Drug [ Time Frame: From baseline up to approximately 5 years ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With the Indicated SAEs and Non-serious AEs Related to Study Drug [ Time Frame: From baseline up to approximately 5 years ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    Certain AEs led to permanent discontinuation of study drug and hence resulted in their withdrawal from the study.

  • Number of Participants With the Indicated >=Grade 3 AEs [ Time Frame: From baseline up to approximately 5 years ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With the Indicated Infusion-related >=Grade 3 AE [ Time Frame: From baseline up to approximately 5 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 37
Study Start Date: March 2009
Study Completion Date: August 2014
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00811733

Locations
United States, California
GSK Investigational Site
Los Angeles, California, United States, 90095-6984
GSK Investigational Site
Stanford, California, United States, 94305
United States, Minnesota
GSK Investigational Site
Rochester, Minnesota, United States, 55905
United States, New York
GSK Investigational Site
Buffalo, New York, United States, 14263
GSK Investigational Site
New York, New York, United States, 10021
United States, Ohio
GSK Investigational Site
Columbus, Ohio, United States, 43210-1228
United States, Texas
GSK Investigational Site
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00811733     History of Changes
Other Study ID Numbers: 110921
Study First Received: December 18, 2008
Results First Received: February 9, 2012
Last Updated: March 26, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Waldenstrom's Macroglobulinemia
Ofatumumab

Additional relevant MeSH terms:
Waldenstrom Macroglobulinemia
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Plasma Cell
Paraproteinemias
Vascular Diseases

ClinicalTrials.gov processed this record on April 26, 2015