A Phase II Study to Determine the Response Kinetics, Safety, and Efficacy of Brentuximab Vedotin and Nivolumab Alone and Then Combined With Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone for Patients With Untreated Primary Mediastinal Large B-Cell Lymphoma
M.D. Anderson Cancer Center
Summary
This phase II trial studies the effect of brentuximab vedotin and nivolumab alone and in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone in treating patients with untreated, stage I-IV primary mediastinal large B-cell lymphoma. Brentuximab vedotin is a monoclonal antibody, called brentuximab, linked to a toxic agent, called vedotin. Brentuximab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD30 receptors, and delivers vedotin to kill them. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Rituximab is a type of antibody therapy, which targets and attaches to the CD20 protein found on the surface of blood cells with cancer and some healthy blood cells. Chemotherapy drugs, such as cyclophosphamide, and doxorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells, or by stopping them from dividing. Prednisone is a steroid, a hormone (chemical messengers) with multiple roles, notably in the immune system and inflammation reduction. Steroids are poisonous to lymphocytes (white blood cells from which lymphomas develop). Giving brentuximab vedotin and nivolumab in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone may help to control the disease and be a less harmful regimen than standard chemotherapy in patients with primary mediastinal large B-cell lymphoma.
Description
PRIMARY OBJECTIVE: I. Evaluate the efficacy of primary mediastinal large B-cell lymphoma (PMBL) patients treated brentuximab vedotin (A) and nivolumab (O) alone and then combined with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP). SECONDARY OBJECTIVE: I. Evaluate the antitumor activity, safety, tolerability, patient reported quality of life and survival of brentuximab vedotin and nivolumab (A-O) alone and then combined with R-CHP in patients with untreated PMBL. EXPLORATORY OBJECTIVE: I. To evaluate the baseline and therapy induced changes in the profile of mutations an…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Histopathologically confirmed diagnosis of PMBL * Require a CD30 expression level of 1% or greater in the tumor or tumor-infiltrating lymphocytes by local immunohistochemistry * No prior treatment except * A prior limited-field radiotherapy * A short course (up to 7 days) of glucocorticoids =\< 100 mg daily of prednisone equivalent which must cease prior to day 1 of cycle 1 * Stage of patients: Stages II, III, IV, and stage I \>= 5 cm in the greatest dimension * Patient or durable power of attorney (DPA) for healthcare must be able to understand and voluntarily s…
Interventions
- DrugBrentuximab Vedotin
Given IV
- DrugCyclophosphamide
Given IV
- DrugDoxorubicin
Given IV
- BiologicalNivolumab
Given IV
- DrugPrednisone
Given PO
- OtherQuality-of-Life Assessment
Ancillary studies
- BiologicalRituximab
Given IV
Location
- M D Anderson Cancer CenterHouston, Texas