Single Agent Ofatumumab Vs. Single Agent Rituximab in Indolent B-Cell Non Hodgkin Lymphoma Relapsed After Rituximab-Containing Therapy

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IIIBiomarker/Laboratory analysis, Treatment18 and over113676
NCI-2012-01195, NCT01200589

Trial Description

Summary

This is a multi-center, parallel, active comparator controlled, open-label, randomized (1:1)

phase III study of single agent ofatumumab compared to single agent rituximab in subjects

with rituximab-sensitive indolent B-cell non hodgkin lymphoma that has relapsed at least 6

months after completing treatment with single agent rituximab or a rituximab-containing

regimen. Subjects must have attained a Complete Response or Partial Response to their last

prior rituximab containing therapy lasting at least six months beyond the end of rituximab

therapy. Subjects will receive four weekly doses of single agent ofatumumab (1000 mg) or

rituximab (375 mg/m2), followed by ofatumumab (1000 mg) or rituximab (375 mg/m2) every 2

months for four additional doses. Therefore, subjects will receive a total of eight doses

of anti-CD20 antibody over 9 months. Subjects will be evaluated for response after

completion of the first four doses of therapy, after six doses of therapy, and after

completion of study therapy. Subjects will be followed until the end of the designated

follow-up period (total study duration of 200 weeks) or until they meet the withdrawal

criteria.

Eligibility Criteria

Inclusion Criteria:

Inclusion Criteria:

1. Indolent NHL subtypes defined according to World Health Organization guidelines:

1. Follicular lymphoma Grades 1, 2, 3 A

2. Small lymphocytic lymphoma (SLL)

3. Marginal zone lymphoma

4. Lymphoplasmacytic lymphoma

2. Rituximab-sensitive iNHL, defined as a partial or complete response to their last

prior treatment with rituximab or a rituximab-containing regimen lasting at least 6

months following completion of rituximab treatment.

3. Relapse or disease progression following response to prior rituximab-based therapy,

as defined by 2007 RRCML criteria, which requires therapy.

4. Radiographically measurable disease, defined as: 2 or more clearly demarcated

lesions/nodes with a long axis >1.5 cm and short axis ≥1.0cm. OR 1 clearly demarcated

lesion/node with a long axis >2.0 cm and short axis ≥1.0cm.

5. ECOG Performance Status of 0, 1, or 2.

6. Age ≥18 years.

7. Life expectancy of at least 6 months in the opinion of the investigator.

8. The patient or their legally acceptable representative must be capable of giving

written informed consent prior to performing any study-specific tests or procedures.

9. All prior treatment related non-hematologic toxicities (with the exception of

alopecia) must have resolved to CTCAE (Version 4.0) ≤ Grade 2 at the time of

randomization.

10. One or more of the following indications for treatment:

1. Cytopenias

2. One or more of the following lymphoma-related symptoms:

Night sweats without signs of infection

Unintentional weight loss (10% within the previous 6 months)

Recurrent, unexplained fever of greater than 100.5F (38C) without signs of

infection

Fatigue which interferes with the patient's quality of life

3. Progressive or massive lymphadenopathy OR

4. Progressive or massive organomegaly French subjects: In France, a subject will

be eligible for inclusion in this study only if either affiliated to or a

beneficiary of a social security category.

Exclusion Criteria:

1. Previous treatment with ofatumumab.

2. Previous anti-CD20 radioimmunotherapy (RIT) or non-rituximab anti-CD20 therapy (such

as obinutuzumab) within 6 months prior to randomization. Patients who have received

previous anti-CD20 RIT or non-rituximab anti-CD20 therapy (such as obinutuzumab) must

have attained a partial or complete response lasting at least 6 months, and must have

recovered from any hematologic or other toxicity.

3. Previous autologous stem cell transplantation within 6 months prior to randomization.

4. Previous allogeneic stem cell transplantation.

5. Previous anti-lymphoma monoclonal antibody therapy (excluding anti-CD20 therapy and

anti-CD20 RIT), chemotherapy, glucocorticoid, or other systemic therapy for lymphoma

within 3 months prior to randomization.

6. Current or previous participation in the treatment phase of another interventional

clinical study within 4 weeks prior to randomization. Patients may continue in the

follow-up phase of another interventional clinical study, but may not have undergone

any treatment on the other study within 4 weeks prior to randomization.

7. Current or previous other malignancy within 2 years prior to randomization. Subjects

who have been free of malignancy for at least 2 years, or have a history of

completely resected non-melanoma skin cancer or successfully treated carcinoma in

situ, are eligible.

8. Chronic or current active infectious disease requiring systemic antibiotics,

antifungal, or antiviral treatment such as, but not limited to, chronic renal

infection, chronic chest infection with bronchiectasis, tuberculosis, active

Hepatitis C, and known HIV disease. All HIV-positive patients are excluded from this

study, regardless of whether they have an Acquired Immunodeficiency Syndrome (AIDS)

defining disease and/or are on antiviral therapy. Prophylactic antiviral and/or

antibacterial antibiotics to prevent recurrence of previous infections are permitted.

9. Clinically significant cardiac disease as judged by the investigator including

unstable angina, acute myocardial infarction within 6 months prior to randomization,

uncontrolled congestive heart failure, and uncontrolled arrhyth

Exclusion Criteria:

Inclusion Criteria:

1. Indolent NHL subtypes defined according to World Health Organization guidelines:

1. Follicular lymphoma Grades 1, 2, 3 A

2. Small lymphocytic lymphoma (SLL)

3. Marginal zone lymphoma

4. Lymphoplasmacytic lymphoma

2. Rituximab-sensitive iNHL, defined as a partial or complete response to their last

prior treatment with rituximab or a rituximab-containing regimen lasting at least 6

months following completion of rituximab treatment.

3. Relapse or disease progression following response to prior rituximab-based therapy,

as defined by 2007 RRCML criteria, which requires therapy.

4. Radiographically measurable disease, defined as: 2 or more clearly demarcated

lesions/nodes with a long axis >1.5 cm and short axis ≥1.0cm. OR 1 clearly demarcated

lesion/node with a long axis >2.0 cm and short axis ≥1.0cm.

5. ECOG Performance Status of 0, 1, or 2.

6. Age ≥18 years.

7. Life expectancy of at least 6 months in the opinion of the investigator.

8. The patient or their legally acceptable representative must be capable of giving

written informed consent prior to performing any study-specific tests or procedures.

9. All prior treatment related non-hematologic toxicities (with the exception of

alopecia) must have resolved to CTCAE (Version 4.0) ≤ Grade 2 at the time of

randomization.

10. One or more of the following indications for treatment:

1. Cytopenias

2. One or more of the following lymphoma-related symptoms:

Night sweats without signs of infection

Unintentional weight loss (10% within the previous 6 months)

Recurrent, unexplained fever of greater than 100.5F (38C) without signs of

infection

Fatigue which interferes with the patient's quality of life

3. Progressive or massive lymphadenopathy OR

4. Progressive or massive organomegaly French subjects: In France, a subject will

be eligible for inclusion in this study only if either affiliated to or a

beneficiary of a social security category.

Exclusion Criteria:

1. Previous treatment with ofatumumab.

2. Previous anti-CD20 radioimmunotherapy (RIT) or non-rituximab anti-CD20 therapy (such

as obinutuzumab) within 6 months prior to randomization. Patients who have received

previous anti-CD20 RIT or non-rituximab anti-CD20 therapy (such as obinutuzumab) must

have attained a partial or complete response lasting at least 6 months, and must have

recovered from any hematologic or other toxicity.

3. Previous autologous stem cell transplantation within 6 months prior to randomization.

4. Previous allogeneic stem cell transplantation.

5. Previous anti-lymphoma monoclonal antibody therapy (excluding anti-CD20 therapy and

anti-CD20 RIT), chemotherapy, glucocorticoid, or other systemic therapy for lymphoma

within 3 months prior to randomization.

6. Current or previous participation in the treatment phase of another interventional

clinical study within 4 weeks prior to randomization. Patients may continue in the

follow-up phase of another interventional clinical study, but may not have undergone

any treatment on the other study within 4 weeks prior to randomization.

7. Current or previous other malignancy within 2 years prior to randomization. Subjects

who have been free of malignancy for at least 2 years, or have a history of

completely resected non-melanoma skin cancer or successfully treated carcinoma in

situ, are eligible.

8. Chronic or current active infectious disease requiring systemic antibiotics,

antifungal, or antiviral treatment such as, but not limited to, chronic renal

infection, chronic chest infection with bronchiectasis, tuberculosis, active

Hepatitis C, and known HIV disease. All HIV-positive patients are excluded from this

study, regardless of whether they have an Acquired Immunodeficiency Syndrome (AIDS)

defining disease and/or are on antiviral therapy. Prophylactic antiviral and/or

antibacterial antibiotics to prevent recurrence of previous infections are permitted.

9. Clinically significant cardiac disease as judged by the investigator including

unstable angina, acute myocardial infarction within 6 months prior to randomization,

uncontrolled congestive heart failure, and uncontrolled arrhyth

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

GlaxoSmithKline

    Trial Sites

    U.S.A.

    Washington
    Seattle

    Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    David G. Maloney
    Principal Investigator

    Link to the current ClinicalTrials.gov record.
    NLM Identifer NCT01200589

    Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.