Phase II intergroup trial of alisertib in relapsed and refractory peripheral T-cell lymphoma and transformed Mycosis fungoides: SWOG 1108 Journal Article

Authors: Barr, P. M.; Li, H.; Spier, C.; Mahadevan, D.; LeBlanc, M.; Ul Haq, M.; Huber, B. D.; Flowers, C. R.; Wagner-Johnston, N. D.; Horwitz, S. M.; Fisher, R. I.; Cheson, B. D.; Smith, S. M.; Kahl, B. S.; Bartlett, N. L.; Friedberg, J. W.
Article Title: Phase II intergroup trial of alisertib in relapsed and refractory peripheral T-cell lymphoma and transformed Mycosis fungoides: SWOG 1108
Abstract: Purpose: Aurora A kinase (AAK) is upregulated in highly proliferative lymphomas, suggesting its potential as a therapeutic target. Alisertib is a novel oral AAK inhibitor without adverse safety signals in early-phase studies that demonstrated preliminary activity in T-cell lymphoma. This phase II study was conducted to further investigate the efficacy of alisertib in relapsed or refractory peripheral T-cell non-Hodgkin lymphoma (PTCL). Patients and Methods: Eligible patients with histologically confirmed relapsed/refractory PTCL or transformed Mycosis fungoides (tMF) received alisertib 50 mg twice a day for 7 days on 21-day cycles. Results: Of 37 eligible patients, the histologic subtypes enrolled included PTCL not otherwise specified (n = 13), angioimmunoblastic T-cell lymphoma (n = 9), tMF (n = 7), adult T-cell lymphoma/leukemia (n = 4), anaplastic large-cell lymphoma (n = 2), and extranodal natural killer/T-cell lymphoma (n = 2). Grade 3 and 4 adverse events in ≥ 5% of patients included neutropenia (32%), anemia (30%), thrombocytopenia (24%), febrile neutropenia (14%), mucositis (11%), and rash (5%). Treatment was discontinued most commonly for disease progression. Among the PTCL subtypes, the overall response rate was 30%, whereas no responses were observed in tMF. Aurora B kinase was more commonly overexpressed than AAK in tumor specimens. Analysis of AAK, Aurora B kinase, MYC, BCL-2, phosphatidylinositol 3-kinase γ, and Notch1 expression revealed no association with response. Conclusion: Alisertib has antitumor activity in PTCL, including heavily pretreated patients. These promising results are being further investigated in an ongoing international, randomized phase III trial comparing alisertib with investigator's choice in PTCL. © 2015 by American Society of Clinical Oncology.
Keywords: adult; treatment response; aged; major clinical study; fatigue; neutropenia; diarrhea; gastrointestinal hemorrhage; side effect; cancer patient; anorexia; protein bcl 2; drug eruption; multiple cycle treatment; pain; phase 2 clinical trial; anemia; leukopenia; mucosa inflammation; thrombocytopenia; creatinine; creatinine blood level; hypercalcemia; abdominal pain; aspartate aminotransferase blood level; backache; febrile neutropenia; fever; hyperglycemia; pneumonia; alkaline phosphatase; aspartate aminotransferase; bilirubin; hyponatremia; hypotension; peripheral t cell lymphoma; multicenter study; myc protein; sepsis; large cell lymphoma; cd4 lymphocyte count; alopecia; leukocytosis; bilirubin blood level; t cell leukemia; mycosis fungoides; skin infection; notch1 receptor; toxic epidermal necrolysis; aurora b kinase; nk t cell lymphoma; angioimmunoblastic t cell lymphoma; alisertib; human; male; female; priority journal; article; phosphatidylinositol 3 kinase gamma
Journal Title: Journal of Clinical Oncology
Volume: 33
Issue: 21
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2015-07-20
Start Page: 2399
End Page: 2404
Language: English
DOI: 10.1200/jco.2014.60.6327
PROVIDER: scopus
PMCID: PMC4500834
PUBMED: 26077240
Notes: Export Date: 2 October 2015 -- Source: Scopus
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  1. Steven M Horwitz
    343 Horwitz