Phase III Randomized, Open Label Study of Single Agent Ofatumumab Vs. Single Agent Rituximab in Follicular Lymphoma Relapsed After Rituximab-Containing Therapy
1. Follicular lymphoma (FL); grades 1, 2 and 3A, defined according to World Health
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
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
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.
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
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
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
14. Current active liver or biliary disease (with the exception of Gilbert's syndrome or
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.