PRIMARY OBJECTIVES:~I. To determine the maximum tolerated dose(s) (MTD)/recommended phase 2 dose(s) (RP2D) of, bortezomib and pegylated liposomal doxorubicin hydrochloride (doxil) when given in combination with fixed dose daratumumab, lenalidomide, and dexamethasone.~SECONDARY OBJECTIVES:~I. To assess the tolerability and safety of the planned regimen, by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration.~II. To estimate and assess overall response rate, response duration, and survival probabilities (overall and progression-free).~EXPLORATORY OBJECTIVES:~I. Quantify CD38+ cells from the peripheral blood mononuclear cells (PBMC) fraction, including T, natural killer (NK), and monocytic subsets.~II. Assess possible changes in CD38 expression, as well as the co-receptor marker CD31, overall and by response status (responder/non-responder).~III. Assess cytokine levels in peripheral blood plasma. IV. Quantify CD38+ cells from the bone marrow CD-138 negative fractions and acellular fractions, including T, NK, and monocytic subsets.~V. Assess possible changes in CD38 expression, as well as the co-receptor marker CD31, overall and by response status (responder/non-responder).~VI. Assess cytokine levels in the bone marrow acellular fraction. VII. Investigate CD38 cellular localization in plasma cells and extracellular vesicles from blood plasma.~VIII. Assess messenger ribonucleic acid (mRNA) expression in the peripheral blood mononuclear cell (PBMC), the bone marrow CD138-negative fraction, the T cell fraction, and plasma cells.~IX. Investigate epigenetic changes in CD38 mRNA expression.~OUTLINE:~Participants receive daratumumab intravenously (IV) on days 1, 8, 15, and 22, dexamethasone IV/orally (PO) on days 1, 2, 8, 9, 15, 16, 22, and 23, pegylated liposomal doxorubicin hydrochloride IV on day 8, lenalidomide PO daily on days 1-14, and bortezomib subcutaneously (SC) on days 1, 4, 8, and 11 of courses 1 and 2. Participants then receive daratumumab IV on days 1, and 15, dexamethasone IV/PO on days 1, 2, 8, 9, 15, 16, 22, and 23, pegylated liposomal doxorubicin hydrochloride IV on day 8, lenalidomide PO daily on days 1-14, and bortezomib SC on days 1, 4, 8, and 11 of courses 3 and 4. Courses repeat every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Participants may receive up to 8 courses at the discretion of treating physician.~After completion of study treatment, participants are followed up at 30 days and then every 3 months for 18 months.
This phase I trial studies side effects of daratumumab, bortezomib, dexamethasone, pegylated liposomal doxorubicin hydrochloride, and lenalidomide in treating participants with plasma cell leukemia. Monoclonal antibodies, such as daratumumab, may interfere with the ability of cancer cells to grow and spread. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as, dexamethasone, pegylated liposomal doxorubicin hydrochloride, and lenalidomide, 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. Giving daratumumab, bortezomib, dexamethasone, pegylated liposomal doxorubicin hydrochloride, and lenalidomide in treating participants with plasma cell leukemia.