Bendamustine and Obinutuzumab in Treating Patents with Previously Untreated Mantle Cell Lymphoma
- Histologically confirmed mantle cell lymphoma (confirmation of cyclin D1 positivity on diagnostic biopsy)
- Subjects must have at least one bi-dimensionally measurable lesion; one of the measurements must be >= 1.5 cm in one dimension
- No prior cytotoxic chemotherapy; prior therapy with single-agent rituximab is permitted; prior involved-field radiotherapy to symptomatic nodal sites of involvement is also permitted
- Prior therapy with rituximab is permitted, even in the setting of rituximab-refractory disease
- Not eligible for more intensive cytotoxic chemotherapy or consolidative autologous stem cell transplant based on one or more of the following: * Clinically significant heart or lung comorbidities, as reflected by at least 1 of the following: ** Left ventricular ejection fraction (LVEF) =< 50% ** Chronic stable angina or congestive heart failure controlled with medication ** New York Heart Association (NYHA) class III or IV heart failure ** Symptomatic chronic pulmonary disease or requirement for intermittent or continuous oxygen therapy * Presence of other medical comorbidity or limitation in functional status which the investigator judges to be incompatible with an acceptable risk to the subject with the use of intensive chemotherapy; the associated comorbidity or functional limitation must be clearly documented in the medical record at the time of enrollment OR
- Subject has been informed of the risks and benefits of intensive chemotherapy and autologous stem cell transplant for treatment of mantle cell lymphoma and has refused this option; this discussion must be clearly documented in the medical record at the time of enrollment
- Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at study entry
- Absolute neutrophil count >= 1500/uL
- Platelet count >= 100,000/uL
- Subjects with neutrophils < 1500/uL or platelets < 100,000/uL with splenomegaly or extensive bone marrow involvement as the etiology for their cytopenias are eligible
- Subjects must have adequate renal function with a creatinine clearance of >= 40 mL/min as determined by the Cockcroft-Gault calculation
- Total bilirubin =< 2 X upper limit laboratory normal (ULN); subjects with non-clinically significant elevations of bilirubin due to Gilbert’s disease are not required to meet these criteria
- Serum transaminases aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 X ULN
- Serum alkaline phosphatase =< 5 X ULN
- Disease-free of prior malignancies for >= 2 years with the exception of basal or squamous cell skin carcinoma, carcinoma “in situ” of the breast or cervix, or localized prostate cancer (treated definitively with hormone therapy, radiotherapy, or surgery)
- Life expectancy of at least 3 months
- Understand and voluntarily sign an informed consent document
- Subjects are not eligible if there is a prior history or current evidence of central nervous system or leptomeningeal involvement
- Concurrent use of other anti-cancer agents or treatments
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent document or complying with the protocol treatment
- Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical or breast cancer, or other cancer from which the subject has been disease free for at least 2 years
- Severe or life-threatening anaphylaxis or hypersensitivity reaction when previously exposed to rituximab or other monoclonal antibody (mAb) therapy
- Known to be positive for human immunodeficiency virus (HIV) or infectious hepatitis (type B or C)
- Pregnant or breast-feeding females
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
I. Progression-free survival (PFS).
I. To estimate the minimal residual disease (MRD) status (MRD defined as reduction >= 10^-6 fold reduction in the IgVH unique clone of mantle cell lymphoma [MCL] by next generation sequencing [NGS]).
II. To estimate the concordance rate between peripheral blood (PB) and bone marrow aspirates in predicting MRD status.
III. To determine objective response rates (complete response [CR] + partial response [PR]) with induction bendamustine + obinutuzumab (BO) in previously untreated MCL using the Lugano classification for response in lymphoma.
IV. To determine overall survival.
V. To determine toxicities observed with induction BO chemoimmunotherapy and obinutuzumab consolidation and maintenance.
INDUCTION CHEMOIMMUNOTHERAPY: Patients receive bendamustine intravenously (IV) over 30-60 minutes on days 1-2 and obinutuzumab IV over 5-7 hours on days 1, 2, 8, and 15 of course 1. Patients also receive bendamustine IV over 30-60 minutes on days 1- 2 and obinutuzumab IV over 4-7 hours on day 1 of courses 2-6. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Beginning 12 weeks after induction chemotherapy, patients receive obinutuzumab IV over 4-7 hours weekly for 4 doses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 8 weeks after consolidation therapy, patients receive obinutuzumab IV over 4-7 hours on day 1. Treatment repeats every 8 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 3 months for 2 years, and then every 6 months for 3 years.
Trial Phase Phase II
Trial Type Treatment
University of Wisconsin Hospital and Clinics
Julie E. Chang
- Primary ID UW16086
- Secondary IDs NCI-2017-01729, 2017-0609
- Clinicaltrials.gov ID NCT03311126