This phase I/II trial studies the side effects and best dose of lenalidomide when given together with combination chemotherapy and to see how well they work in treating patients with MYC-associated B-cell lymphomas. Lenalidomide may stop the growth of B-cell lymphomas by blocking the growth of new blood vessels necessary for cancer growth and by blocking some of the enzymes needed for cell growth. Biological therapies, such as lenalidomide, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as etoposide, prednisone, vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, 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. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving lenalidomide together with combination chemotherapy may be an effective treatment in patients with B-cell lymphoma.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02213913.
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of lenalidomide when added to dose-adjusted (DA)-etoposide, prednisone, vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, rituximab (EPOCH-R) in patients with double hit lymphoma (DHL) lymphomas. (Phase I)
II. To determine the 1- and 2-year progression free survival (PFS) of DA-EPOCH-R in subjects with DHL lymphomas. (Phase II)
SECONDARY OBJECTIVES:
I. Determine the overall response rate, complete response, and duration of response.
II. Measure the quality of life (QOL) using standardized scale.
III. Assess the toxicity profile assessment using version 4.0 of the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) criteria.
IV. Evaluate the overall survival (OS) at 1 and 2 years.
OUTLINE: This is a phase I, dose-escalation study of lenalidomide followed by a phase II study.
INDUCTION PHASE: Patients receive lenalidomide orally (PO) daily on days 1-14. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
DA-EPOCH-R: Patients receive etoposide intravenously (IV) continuously on days 1-4, prednisone PO twice daily (BID) on days 1-5, vincristine sulfate IV continuously on days 1-4, doxorubicin hydrochloride IV continuously on days 1-4, cyclophosphamide IV over 15 minutes on day 5, and rituximab IV over 4 hours on day 1 (per institutional guidelines). Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION PHASE: Patients who are transplantation (hematopoietic stem cell transplant [HSCT])-eligible receive BCNU, etoposide, cytarabine, and melphalan (BEAM)-conditioning regimen followed by autologous (auto)-HSCT or HSCT at the discretion of the treating physician. Patients who do not undergo HSCT and are currently in first remission receive lenalidomide PO on days 1-14 within 8 weeks of last dose of chemotherapy. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, and then periodically thereafter.
Lead OrganizationUniversity of Chicago Comprehensive Cancer Center
Principal InvestigatorSonali Mehta Smith
