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Ref Type Journal Article
PMID (30082475)
Authors Kelly KR, Friedberg JW, Park SI, McDonagh K, Hayslip J, Persky D, Ruan J, Puvvada S, Rosen P, Iyer SP, Stefanovic A, Bernstein SH, Weitman S, Karnad A, Monohan G, VanderWalde A, Mena R, Schmelz M, Spier C, Groshen S, Venkatakrishnan K, Zhou X, Sheldon-Waniga E, Leonard EJ, Mahadevan D
Title Phase I Study of the Investigational Aurora A Kinase Inhibitor Alisertib plus Rituximab or Rituximab/Vincristine in Relapsed/Refractory Aggressive B-cell Lymphoma.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 24
Issue 24
Date 2018 Dec 15
URL
Abstract Text The aurora A kinase inhibitor alisertib demonstrated single-agent clinical activity and preclinical synergy with vincristine/rituximab in B-cell non-Hodgkin lymphoma (B-NHL). This phase I study aimed to determine the safety and recommended phase II dose (RP2D) of alisertib in combination with rituximab ± vincristine in patients with relapsed/refractory aggressive B-NHL.Patients with relapsed/refractory, diffuse, large, or other aggressive B-NHL received oral alisertib 50 mg b.i.d. days 1 to 7, plus i.v. rituximab 375 mg/m2 on day 1, for up to eight 21-day cycles (MR). Patients in subsequent cohorts (3 + 3 design) received increasing doses of alisertib (30 mg starting dose; 10 mg increments) b.i.d. days 1 to 7 plus rituximab and vincristine [1.4 mg/m2 (maximum 2 mg) days 1, 8] for 8 cycles (MRV). Patients benefiting could continue single-agent alisertib beyond 8 cycles. Cell-of-origin and MYC/BCL2 IHC was performed on available archival tissue.Forty-five patients participated. The alisertib RP2D for MR was 50 mg b.i.d. For MRV (n = 32), the RP2D was determined as 40 mg b.i.d. [1 dose-limiting toxicity (DLT) at 40 mg; 2 DLTs at 50 mg]. Drug-related adverse events were reported in 89% of patients, the most common was neutropenia (47%). Seven patients had complete responses (CR), 7 had partial responses (PRs); 9 of 20 (45%) patients at the MRV RP2D responded (4 CRs, 5 PRs), all with non-germinal center B-cell (GCB) diffuse large B-cell lymphoma (DLBCL).The combination of alisertib 50 mg b.i.d. plus rituximab or alisertib 40 mg b.i.d. plus rituximab and vincristine was well tolerated and demonstrated activity in non-GCB DLBCL.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown B-cell lymphoma not applicable Alisertib + Rituximab + Vincristine Sulfate Phase I Actionable In a Phase I trial, Alisertib (MLN8237) in combination with Rituxan (rituximab) and Oncovin (vincristine) demonstrated safety and efficacy, resulted in an objective response rate of 38% (14/37, 7 complete response, 7 partial response), and stable disease in 32% (12/37) of patients with relapsed or refractory B-cell non-Hodgkin lymphomas (PMID: 30082475; NCT01397825). 30082475
Unknown unknown B-cell lymphoma not applicable Alisertib + Rituximab Phase I Actionable In a Phase I trial, Alisertib (MLN8237) in combination with Rituxan (rituximab) demonstrated safety and efficacy, resulted in an objective response rate of 25% (3/12, 2 complete response, 1 partial response), and stable disease in 42% (5/12) of patients with relapsed or refractory B-cell non-Hodgkin lymphomas (PMID: 30082475; NCT01397825). 30082475