Phase I/II Study of Bendamustine in Combination With Ofatumumab, Carboplatin and Etoposide for Refractory or Relapsed Aggressive B-cell Lymphomas
The Phase I part of the study will apply to identify dose-limiting toxicities (DLT) and to define maximum-tolerated dose (MTD) for a new chemoimmunotherapy combination of bendamustine, ofatumumab, carboplatin, and etoposide in patients with Non Hodgkin's lymphoma whose disease has progressed or has recurred after prior chemotherapy. The Phase II part of the study will be a single-arm, open-label study in which all patients will receive combination bendamustine, ofatumumab, carboplatin and etoposide at the MTD dose defined in phase I. This study hopes to identify a life-prolonging therapy for patients with Non-Hodgkin's Lymphoma whose disease has progressed or has recurred after prior chemotherapy. The hypothesis is that the proposed combination of chemotherapy is well-tolerated and is efficacious for the treatment of relapsed/refractory aggressive B cell lymphomas.
• 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.