Phase I/II Study of Bendamustine in Combination With Ofatumumab, Carboplatin and Etoposide

Inclusion Criteria

• Age 18 and above
• Patients with histologically confirmed DLBCL, including primary mediastinal large B cell lymphoma, T cell rich B cell lymphoma, "double hit" DLBCL, mantle cell lymphoma, any transformed low grade B cell lymphomas or grade 3 follicular lymphoma (Grade 3a or 3b) who were refractory to RCHOP-like or any anthracycline based chemotherapy or relapsed after at least one prior combination chemotherapeutic regimen and who are deemed candidates for a salvage type chemotherapy.
• Relapsed disease:
• Progressive disease after a CR for at least 28 days. Progression will be defined according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2007 (33)).
• Refractory disease (Subjects must meet one of the following criteria):
• Persistent or progressive lymphoma with a CR of <28 days duration or with a PR of any duration. Subjects must have received at least 3 cycles of RCHOP-like or any anthracycline base chemotherapy or at least 2 full cycles of HyperCVAD-like chemotherapy.
• Persistent lymphoma and stable disease after at least 2 cycles of RCHOP-like or any anthracycline base chemotherapy or at least 1 full cycle of HyperCVAD-like chemotherapy (part A and B).
• Progressive disease despite at least 1 cycle of RCHOP-like or any anthracycline base chemotherapy or at least 1 cycle (part A or A and B) of HyperCVAD-like chemotherapy.
• Measurable disease, defined by the revised lymphoma criteria (Cheson 2007).
• Absolute neutrophil count ≥1, 500 and platelet count ≥ 75,000, unless due to underlying lymphoma.
• Left ventricular ejection fraction estimated by MUGA scan or 2D-echocardiogram of at least 45% Cardiology consult is recommended prior to enrollment if a history of coronary artery disease, CHF with estimated LVEF of <50% or clinically significant arrhythmia.
• Estimated glomerular filtration rate (GFR) must be ≥ 50 mL/min
• Serum bilirubin ≤ 1.5 × upper limit of normal (ULN) unless deemed elevated secondary to lymphoma involvement of the liver or known Gilbert's syndrome.
• Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 2.5 × ULN; unless elevated secondary to lymphoma involvement of the liver
• Alkaline phosphatase ≤ 2.5 × ULN; unless elevated secondary to lymphoma involvement of the liver.
• Performance status of ECOG 0-2.
• Both potentially AutoSCT or AlloSCT candidates and those who are not transplant candidates are eligible for the study.
• Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent and HIPAA consent.
• Female patients of childbearing potential must have a negative serum pregnancy test within 3 days prior to enrollment.
• Male and female patients of reproductive potential must use an effective contraceptive method during the study and for a minimum of 1 year after the after study treatment.
• Must be able to comply with study and follow up requirements.

Exclusion Criteria

• Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
• Use of investigational agents within 4 weeks prior to enrollment.
• Any anticancer therapy within 3 weeks before study entry. The patient must have recovered from all acute toxicities from any previous therapy.
• Radioimmunotherapy (i.e. Zevalin) within 8 weeks of enrollment.
• Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 4 weeks prior to start of therapy.
• Autologous stem cell rescue within 12 weeks before study enrollment or those who underwent allogeneic stem cell transplant within one year of enrolment.
• Known leptomeningeal or parenchymal brain involvement with lymphoma unless in complete remission after treatment for at least 12 weeks with negative CSF cytology within 2 weeks. Prophylaxis of CNS disease using intrathecal dosing of cytotoxic regimens is permitted and should be performed according to the discretion of the treating