Single Agent Ofatumumab Vs. Single Agent Rituximab in Follicular 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 grade 1, 2, and 3A follicular 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. Follicular lymphoma (FL); grades 1, 2 and 3A, defined according to World Health

Organization guidelines.

2. Rituximab-sensitive FL, defined as a partial or complete response to treatment with

rituximab or a rituximab-containing regimen lasting at least 6 months following

completion of the last rituximab treatment.

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

as defined by 2007 Revised Response Criteria for Malignant Lymphoma criteria, which

requires therapy.

4. Radiographically measurable disease, defined as at least one clearly demarcated

lesion with a largest diameter ≥ 2.0 cm by CT scan imaging.

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.

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 radioimmunotherapy (RIT) within 6 months of randomization. Patients who

have received previous RIT 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 of randomization.

4. Previous allogeneic stem cell transplantation.

5. Previous anti-lymphoma monoclonal antibody therapy (excluding rituximab),

chemotherapy, glucocorticoid, or other systemic therapy for lymphoma within 3 months

of randomization.

6. Current or previous participation in another interventional clinical study within 4

weeks of randomization.

7. Current or previous other malignancy within 2 years of 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.

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

unstable angina, acute myocardial infarction within 6 months of randomization,

congestive heart failure, and arrhythmia requiring therapy.

10. Other significant concurrent, uncontrolled medical conditions including, but not

limited to, renal, hepatic, autoimmune, hematological, gastrointestinal, endocrine,

pulmonary, neurological, cerebral or psychiatric disease which, in the investigator's

opinion, will impact study participation.

11. Screening laboratory values:

1. Neutrophils < 1.5 x 109/L (unless due to FL involvement of the bone marrow).

2. Platelets < 50 x 109/L (unless due to FL involvement of the bone marrow).

3. ALT or AST > 2xULN, alkaline phosphatase and bilirubin > 1.5xULN (isolated

predominantly indirect hyperbilirubinemia due to Gilbert's syndrome is

acceptable for inclusion)

12. Known or suspected inability to fully comply with study protocol

a. Lactating women. b. Women with a positive pregnancy test at study entry c. Men with

partners of childbearing potential and women of childbearing potential who are not willing

to use adequate contraception from study entry through one year following last treatment

dose.

14. Current active liver or biliary disease (with the exception of Gilbert's syndrome or

asymptomatic gallstones).

15. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In

addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA

test will be performed and if positive the subject will be excluded.

Exclusion Criteria:

Inclusion Criteria:

1. Follicular lymphoma (FL); grades 1, 2 and 3A, defined according to World Health

Organization guidelines.

2. Rituximab-sensitive FL, defined as a partial or complete response to treatment with

rituximab or a rituximab-containing regimen lasting at least 6 months following

completion of the last rituximab treatment.

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

as defined by 2007 Revised Response Criteria for Malignant Lymphoma criteria, which

requires therapy.

4. Radiographically measurable disease, defined as at least one clearly demarcated

lesion with a largest diameter ≥ 2.0 cm by CT scan imaging.

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.

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 radioimmunotherapy (RIT) within 6 months of randomization. Patients who

have received previous RIT 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 of randomization.

4. Previous allogeneic stem cell transplantation.

5. Previous anti-lymphoma monoclonal antibody therapy (excluding rituximab),

chemotherapy, glucocorticoid, or other systemic therapy for lymphoma within 3 months

of randomization.

6. Current or previous participation in another interventional clinical study within 4

weeks of randomization.

7. Current or previous other malignancy within 2 years of 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.

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

unstable angina, acute myocardial infarction within 6 months of randomization,

congestive heart failure, and arrhythmia requiring therapy.

10. Other significant concurrent, uncontrolled medical conditions including, but not

limited to, renal, hepatic, autoimmune, hematological, gastrointestinal, endocrine,

pulmonary, neurological, cerebral or psychiatric disease which, in the investigator's

opinion, will impact study participation.

11. Screening laboratory values:

1. Neutrophils < 1.5 x 109/L (unless due to FL involvement of the bone marrow).

2. Platelets < 50 x 109/L (unless due to FL involvement of the bone marrow).

3. ALT or AST > 2xULN, alkaline phosphatase and bilirubin > 1.5xULN (isolated

predominantly indirect hyperbilirubinemia due to Gilbert's syndrome is

acceptable for inclusion)

12. Known or suspected inability to fully comply with study protocol

a. Lactating women. b. Women with a positive pregnancy test at study entry c. Men with

partners of childbearing potential and women of childbearing potential who are not willing

to use adequate contraception from study entry through one year following last treatment

dose.

14. Current active liver or biliary disease (with the exception of Gilbert's syndrome or

asymptomatic gallstones).

15. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In

addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA

test will be performed and if positive the subject will be excluded.

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.