This phase II trial studies how well rituximab, brentuximab vedotin, and bendamustine work in treating patients with newly diagnosed post transplant lymphoproliferative disorder. Immunotherapy with monoclonal antibodies, such as rituximab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Brentuximab vedotin is a monoclonal antibody, called brentuximab, linked to a chemotherapy drug called vedotin. Brentuximab attached to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. Chemotherapy drugs, such as bendamustine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding brentuximab vedotin to rituximab or to rituximab and bendamustine may kill more cancer cells in patients with post transplant lymphoproliferative disorder.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04138875.
PRIMARY OBJECTIVE:
I. Determine the overall response rate (ORR) at the end of therapy (complete + partial response rate), and progression free survival (PFS) of the combination of rituximab, brentuximab vedotin +/- bendamustine in patients with newly diagnosed polymorphic and monomorphic CD20+ and CD30+ post transplant lymphoproliferative disorders (PTLD).
SECONDARY OBJECTIVES:
I. Determine the ORR at the end of the induction phase with rituximab and brentuximab vedotin (RBv) in patients with newly diagnosed polymorphic and monomorphic CD20+ and CD30+ PTLD.
II. Determine the duration of response (DOR) and overall survival (OS) of the combination of rituximab, brentuximab vedotin +/-bendamustine in patients with newly diagnosed polymorphic and monomorphic CD20+ and CD 30+ PTLD.
III. Determine the frequency of infections and peripheral sensory neuropathy, the rates of graft rejection and the treatment related mortality in patients with newly diagnosed polymorphic and monomorphic CD20+ CD30+ PTLD treated with the combination of rituximab, brentuximab vedotin +/-bendamustine.
EXPLORATORY OBJECTIVE:
I. The trial will aim to identify biological and genetic markers that may predict response or resistance to this therapeutic combination.
OUTLINE:
INDUCTION: Patients receive rituximab intravenously (IV) on days 1, 8, 15, and 22 and brentuximab vedotin IV over 30 minutes on days 1, 8, 15 in the absence of disease progression or unacceptable toxicity. Patients are then assigned to 1 of 2 arms.
ARM I: Patients with low risk receive rituximab IV and brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
ARM II: Patients with high risk receive rituximab IV and brentuximab vedotin IV over 30 minutes on day 1, and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with complete response or partial response then receive additional 2 cycles of treatment in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year.
Lead OrganizationNYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
Principal InvestigatorFrancesca Montanari
