Abstract

The present sequential trial design takes advantage of a window of opportunity to assess PS-341 alone in aggressive large cell lymphomas. However, because recurrent DLBCL is potentially curable with EPOCH chemotherapy alone ( 20%) or stem cell transplant ( 25%), patients who do not enter CR with PS-341 will receive PS-341 and EPOCH chemotherapy. EPOCH chemotherapy was selected because its efficacy has been validated in both recurrent and untreated DLBCL and is a potentially curable regimen. Hence, if PS-341 is shown to be active, it could potentially be combined with EPOCH for the initial treatment of poor prognosis NF-kB-expressing DLBCL. 1.1. Study Objectives Primary 1.1.1 Assess response of PS-341 in diffuse large B-cell lymphoma (DLBCL) and within the ABC and GCB molecular subtypes. 1.1.2 Assess toxicity and safe tolerated dose of PS-341 and EPOCH in DLBCL. 1.1.3 Obtain pilot information on response of PS-341 and EPOCH in DLBCL. Secondary 1.1.4 Assess biological effect of PS-341 on DLBCL tumor biopsies using microarray and IHC, including bcl-2 and NF-kB. 1.1.5 Assess markers of drug resistance (bcl-2, MIB-1, p53) on response to PS-341 and EPOCH.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010717-11
Application #
9343679
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Kreitman, Robert J; Tallman, Martin S; Robak, Tadeusz et al. (2018) Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase 1 results and long-term follow-up. Blood 131:2331-2334
Melani, Christopher; Wilson, Wyndham H; Roschewski, Mark (2018) What is the standard of care for primary mediastinal b-cell lymphoma; R-CHOP or DA-EPOCH-R? Br J Haematol :
Melani, Christopher; Roschewski, Mark; Wilson, Wyndham H (2018) End-of-treatment and serial PET imaging has prognostic value and clinical utility in primary mediastinal B-cell lymphoma following dose-adjusted EPOCH-R - Response to Adams et al. Haematologica 103:e382
Kreitman, Robert J; Dearden, Claire; Zinzani, Pier Luigi et al. (2018) Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia 32:1768-1777
Melani, Christopher; Advani, Ranjana; Roschewski, Mark et al. (2018) End-of-treatment and serial PET imaging in primary mediastinal B-cell lymphoma following dose-adjusted EPOCH-R: a paradigm shift in clinical decision making. Haematologica 103:1337-1344
Younes, Anas; Ansell, Stephen; Fowler, Nathan et al. (2017) The landscape of new drugs in lymphoma. Nat Rev Clin Oncol 14:335-346
Mailankody, Sham; Kazandjian, Dickran; Korde, Neha et al. (2017) Baseline mutational patterns and sustained MRD negativity in patients with high-risk smoldering myeloma. Blood Adv 1:1911-1918
Dimitriades, Victoria R; Devlin, Vincent; Pittaluga, Stefania et al. (2017) DOCK 8 Deficiency, EBV+ Lymphomatoid Granulomatosis, and Intrafamilial Variation in Presentation. Front Pediatr 5:38
Navarro, Alba; Clot, Guillem; Martínez-Trillos, Alejandra et al. (2017) Improved classification of leukemic B-cell lymphoproliferative disorders using a transcriptional and genetic classifier. Haematologica 102:e360-e363
Melani, Christopher; Major, Ajay; Schowinsky, Jeffrey et al. (2017) PD-1 Blockade in Mediastinal Gray-Zone Lymphoma. N Engl J Med 377:89-91

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