Ann Arbor Stage I Primary Mediastinal (Thymic) Large B-Cell Lymphoma Clinical Trial
Official title:
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
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.
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 and gene expression. OUTLINE: Patient will receive an immune lead-in of 2 cycles of Brentuximab vedotin and Nivolumab (A-O) (cycles 1 and 2), which has an appropriate futility rules in place to close early if efficacy targets are not met. At cycle 3 and 4, patients will receive A-O with R-CHP. Patients who will have achieved complete response (CR) at PET/CT before cycle 5 will receive 2 more cycles of A-O-R-CHP (cycle 5 and 6) and A-O only for cycle 7 and 8. If these patients still present CR at PET/CT after cycle 8, they will have completed therapy and will be followed up. In case of stable disease or progressive disease at PET/CT after cycle 4, the patient will be taken off the trial. Patients who present further response but no CR, at PET/CT before cycle 5 will receive 4 more cycles A-O-R-CHP (cycles 5-8). If they reach CR at PET/CT after cycle 8, they will have completed therapy and will be followed up. All patients will receive a total of 8 cycles of A-O. The cycle duration is 21 days. Brentuximab vedotin will be given intravenously (IV) over 30 minutes and nivolumab IV over 30 minutes on day 1. R-CHP: rituximab IV will be administered over 4-6 hours, cyclophosphamide IV over 1 hour, and doxorubicin IV over 1 hour on day 1, and prednisone orally (PO) once daily (QD) on days 1-5. After completion of study treatment, patients are followed up every 3 months for 1 year, and then every 4 months for 1 year. ;