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Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

ABSTRACT: This phase I trial studies the side effects and the best dose of alisertib when given together with vorinostat in treating patients with Hodgkin lymphoma, B-cell non-Hodgkin lymphoma, or peripheral T-cell lymphoma that has come back. Alisertib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

DISEASE(S): Adult T Acute Lymphoblastic Leukemia,Lymphoma, Large-cell, Immunoblastic,Mature T-cell And Nk-cell Non-hodgkin Lymphoma,Adult B Acute Lymphoblastic Leukemia,Precursor T-cell Lymphoblastic Leukemia-lymphoma,Recurrent Grade 1 Follicular Lymphoma,Refractory Hairy Cell Leukemia,Chronic Lymphocytic Leukemia,Sezary Syndrome,T-cell Large Granular Lymphocyte Leukemia,Splenic Marginal Zone Lymphoma,Leukemia, Hairy Cell,Refractory Chronic Lymphocytic Leukemia,Mycosis Fungoides,Lymphoma, Mantle-cell,Leukemia-lymphoma, Adult T-cell,Recurrent Primary Cutaneous T-cell Non-hodgkin Lymphoma,Recurrent Adult Burkitt Lymphoma,Leukemia, T-cell,Lymphomatoid Granulomatosis,Lymphoma, T-cell, Peripheral,Plasmablastic Lymphoma,Lymphoma, B-cell, Marginal Zone,Burkitt Lymphoma,Extranodal Marginal Zone Lymphoma Of Mucosa-associated Lymphoid Tissue,Recurrent Small Lymphocytic Lymphoma,Recurrent Mycosis Fungoides And Sezary Syndrome,Lymphoma, T-cell, Cutaneous,Recurrent Marginal Zone Lymphoma,Recurrent Adult Grade Iii Lymphomatoid Granulomatosis,Lymphoma, Follicular,Waldenstrom Macroglobulinemia,Recurrent Adult Immunoblastic Lymphoma,Small Intestinal Lymphoma,Leukemia, Lymphocytic, Chronic, B-cell,Intraocular Lymphoma,Recurrent Mantle Cell Lymphoma,Recurrent Adult Acute Lymphoblastic Leukemia,Recurrent Grade 3 Follicular Lymphoma,Hodgkin Disease,Leukemia,Recurrent Adult Hodgkin Lymphoma,Mycoses,Angioimmunoblastic T-cell Lymphoma,Recurrent Adult Lymphoblastic Lymphoma,Leukemia, Large Granular Lymphocytic,Testicular Lymphoma,Lymphomatous Involvement Of Non-cutaneous Extranodal Site,Nodal Marginal Zone Lymphoma,Lymphoma, Large-cell, Anaplastic,Lymphoma, T-cell,Primary Cutaneous B-cell Non-hodgkin Lymphoma,Hepatosplenic T-cell Lymphoma,Leukemia, Lymphoid,Immunoblastic Lymphadenopathy,Precursor Cell Lymphoblastic Leukemia-lymphoma,Lymphoma,Recurrent Non-hodgkin Lymphoma,Anaplastic Large Cell Lymphoma,Recurrent Grade 2 Follicular Lymphoma,Recurrent Adult T-cell Leukemia/lymphoma,Lymphoma, Non-hodgkin,Lymphoma, B-cell

PROVIDER: 2123001 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Background Epigenetic changes are involved in the extinction of the B-cell gene expression program of classical Hodgkin lymphoma. However, little is known regarding epigenetic similarities between classical Hodgkin lymphoma and plasma cell myeloma cells, both of which share an extinction of the gene expression program of mature B-cells. Design and methods Global histone H3 acetylation patterns were determined in cell lines derived from classical Hodgkin lymphoma, plasma cell myeloma and B-cell lymphoma by chromatin immunoprecipitation and subsequent hybridization onto promoter tiling arrays. H3K27 trimethylation was analyzed by chromatin immunoprecipitation and real-time DNA-PCR for selected genes. Epigenetic modifications were compared to gene expression data. Results B-cell characteristic genes were hypoacetylated in classical Hodgkin lymphoma and plasma cell myeloma cell lines, as demonstrated by comparison of their histone H3 acetylation patterns to those of B-cell lines. However, the number of genes jointly hyperacetylated and expressed in classical Hodgkin lymphoma and plasma cell myeloma cell lines, such as IFR4/MUM1 and RYBP, is limited. Moreover, H3K27 trimethylation for selected B-cell characteristic genes revealed that this additional epigenetic silencing is much more prevalent in classical Hodgkin lymphoma as compared to plasma cell myeloma. Conclusion Our epigenetic data support the view that classical Hodgkin lymphoma is characterized by an abortive plasma cell differentiation with a down-regulation of B-cell characteristic genes but without activation of most plasma cell typical genes. Gene expression analysis of Hodgkin lymphoma (cHL) and B-cell lines: Microarray data for three Hodgkin lymphoma cell lines (KM-H2, L1236, L428) and the B-cell line Namalwa that were published previously by our group (GEO accession GSE8388) were analyzed together with newly generated data for the B-cell lines SU-DHL4 and SU-DHL6. For all cell lines, RNA was isolated according to standard protocols (Qiagen, Hilden, Germany) and used for Affymetrix GeneChip hybridization (HG-U133A). Microarrays were normalized using RMA, and differential expression was calculated using moderated t-test. The gene expression profiles of the cell lines were generated in duplicates.

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Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

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