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Rituximab, Brentuximab Vedotin, and Bendamustine for the Treatment of Newly Diagnosed Post Transplant Lymphoproliferative Disorders

Trial Status: Active

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.

Inclusion Criteria

  • Patient must have histologically confirmed newly diagnosed polymorphic or monomorphic PTLD defined according to the 2017 World Health Organization (WHO) classification criteria, with positive CD20 expression and >= 1% CD30 expression
  • Diagnostic archival tissue available for review and correlative studies
  • Previous solid organ or allogeneic hematopoietic stem cell transplant
  • Measurable disease by positron emission tomography (PET)/computed tomography (CT) based on the Lugano Criteria
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Serum creatinine =< 2 mg/dl or creatinine clearance >= 30 ml/min (estimated by Cockcroft-Gault equation)
  • Total bilirubin =< 1.5 x institutional upper limit of normal
  • Aspartate transaminase (AST) and alanine transaminase (ALT) =< 2.5 x institutional upper limit of normal
  • Absolute neutrophil count (ANC) >= 1000/uL
  • Platelet count >= 75000/uL
  • Negative urine or serum pregnancy test for women of childbearing potential. All women of childbearing potential must agree to use an effective barrier method of contraception (either an intrauterine device or double-barrier method using condoms or a diaphragm plus spermicide) during the treatment period and for at least 6 months after discontinuation of the study drugs. Male subjects should use effective barrier method of contraception during the treatment period and for at least 6 months after discontinuation of the study drugs
  • Patients must be able to understand and to sign a written consent document

Exclusion Criteria

  • Previous treatment for PTLD with the exception of immunosuppression reduction and rituximab single agent for Epstein-Barr virus (EBV) viremia, prior to the diagnosis of PTLD known involvement of the central nervous system by the PTLD
  • Known allergic reactions against foreign proteins
  • Uncontrolled inter-current illness including active infection, acute graft versus host disease and/or transplant organ rejection
  • Active concurrent malignancy with the exception of non-melanoma skin cancer, carcinoma in situ of the cervix or localized prostate cancer
  • Severe non-compensated diabetes mellitus
  • Pre-existing neuropathy grade 2 or greater
  • Pregnant or lactating
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with previous hypersensitivity to rituximab
  • Known human immunodeficiency virus (HIV) positive

Minnesota

Rochester
Mayo Clinic in Rochester
Status: APPROVED
Contact: Jamie Johnston
Phone: 507-284-2333

New York

New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: ACTIVE
Contact: Francesca Montanari

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.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center

Principal Investigator
Francesca Montanari

  • Primary ID AAAS3998
  • Secondary IDs NCI-2020-01556
  • Clinicaltrials.gov ID NCT04138875