A Phase II Open-Label Study of Ofatumumab and Bendamustine Followed by Maintenance Ofatumumab for Indolent B-cell Non-Hodgkin's Lymphoma (B-NHL) Which Has Relapsed After Rituximab or a Rituximab Containing Therapy
- Signed written informed consent
- Small lymphocytic, lymphoplasmacytic, marginal zone lymphoma, and follicular
lymphoma; Grades 1, 2 and 3a, defined according to World Health organization (WHO)
guidelines. [Tefferi, 2008]
- Tumor verified to be CD20+ (based on local evaluation), from a current or previous
tissue biopsy. Tissue biopsy should be repeated if no report or specimen is
available, CD20 staining was not previously performed, or there is clinical suspicion
that the indolent lymphoma has transformed to aggressive lymphoma/higher malignancy
- Rituximab-sensitive disease, defined as a Partial Remission (PR) or Complete
Remission (CR) to the last rituximab-containing therapy lasting at least 6 months
following completion of therapy. Last rituximab-containing therapy is defined as the
last therapy regimen containing at least one full dose of rituximab.
- Relapse or disease progression following response to prior rituximab-based therapy,
requiring treatment by 2007 Revised Response Criteria for Malignant Lymphoma (RRCML)
- CT imaging in screening (based on local evaluation) showing 2 or more clearly
demarcated lesions with a largest diameter > 1.5 cm, or 1 clearly demarcated lesion
with a largest diameter > 2.0 cm.
- ECOG Performance Status of 0, 1, or 2.
- Age ≥ 18 years.
- Life expectancy of at least 6 months in the opinion of the investigator.
- Women of childbearing potential must have a negative serum pregnancy test within 14
days of first dose of study treatment and agree to use effective contraception during
the study and for one year following the last dose of study drug.
- Men with a female partner of childbearing potential must have either had a prior
vasectomy or agree to use effective contraception from 2 weeks prior to
administration of the first dose of study treatment until one year after the last
dose of study treatment.
- Must not be on any prohibited medications.
- Subjects who have received prior bendamustine are eligible if they achieved a
response (CR/PR) which lasted > 6 months after the end of bendamustine containing
- Lactating women
- CLL, Grade 3b follicular lymphoma or evidence that the indolent lymphoma has
transformed to aggressive lymphoma. Subjects suspicious for transformation should
undergo a biopsy to exclude the possibility of transformation. Subjects with a
previous diagnosis of small lymphocytic leukemia (SLL) and a screening monoclonal
B-lymphocyte count of ≥ 5000/µl are defined by 2008 International Workshop on Chronic
Lymphocytic Leukemia (IWCLL) criteria to have CLL; such patients are NOT eligible for
- Rituximab-refractory disease, defined as failure to respond to or progression within
6 months of completing rituximab or rituximab-containing combination therapy.
- Previous treatment with ofatumumab.
- Previous radioimmunotherapy (RIT) within 6 months of study entry. Subjects who have
received RIT must have attained a PR or CR lasting at least 6 months, and must have
recovered from any hematologic or other toxicity.
- Previous allogeneic stem cell transplantation at any time OR autologous stem cell
transplantation within 6 months of study entry.
- Prior use of monoclonal antibody (other than anti CD20) within 3 months prior to
randomization. Chemotherapy or other systemic lymphoma therapy within 4 weeks of
- Received treatment with an investigational agent within 4 weeks of study entry, or is
actively participating in another interventional clinical study.
- Known Central Nervous System (CNS) involvement by lymphoma.
- Current or previous other malignancy within 2 years of study entry. Exception:
Subjects who have been disease-free for 2 years or more, or subjects with a history
of completely resected non-melanoma skin cancer or successfully treated in situ
carcinoma are eligible.
- Chronic or currently active infectious disease requiring systemic antibiotics,
antifungal, or antiviral treatment including, but not limited to: chronic renal
infection, chronic chest infection with bronchiectasis, tuberculosis, active
Hepatitis C, and known HIV disease. All Human Immunodeficient virus (HIV)-positive
subjects are excluded from this study, regardless of whether they have an Acquired
Immunodeficiency Syndrome (AIDS) defining disease and/or are on antiviral therapy.
- Clinically significant cardiac disease including unstable angina, acute myocardial
infarction within 6 months of study entry, uncontrolled congestive heart failure, and
uncontrolled arrhythmia. Subjects with congestive heart disease or arrhythmia such as
atrial fibrillation whose cardiac disease is well controlled on a stable medical
regimen are eligible.
- 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.
- Positive serology for Hepatitis B (HB) defined as a positive test for Hepatitis B
surface antigen (HBsAg). In addition, if negative for HBsAg but (Hepatitis B core
antibody (HBcAb) positive (regardless of Hepatitis B surface antibody [HBsAb]
status), a HB DNA test will be performed and if positive the subject will be
excluded. If HBV DNA is negative, subject may be included but must undergo HBV DNA
monitoring. Prophylactic antiviral therapy may be initiated at the discretion of the
- Current active liver or biliary disease. Exception: Subjects with Gilbert's syndrome
or asymptomatic gallstones, liver metastases related to indolent NHL or otherwise
stable chronic liver disease per investigator assessment, are eligible.
- Screening laboratory values:
Neutrophils < 1.5 x 109/L (unless due to NHL involvement of the bone marrow). Platelets <
100 x 109/L (unless due to NHL involvement of the bone marrow). Serum creatinine ≥2.0
mg/dL; subjects with serum creatinine ≥2.0 mg/dL are eligible if the creatinine clearance
(Cockcroft Gault equation [Cockcroft, 1976]) is ≥40 mL/min.
Total bilirubin > 1.5 times ULN [upper normal limit] (unless due to liver involvement by
NHL or Gilbert's disease).
Transaminases > 3 times ULN (unless due to NHL involvement).
- Known or suspected inability to fully comply with study protocol.
- Known or suspected hypersensitivity to ofatumumab, bendamustine or mannitol.