Multi-institutional phase 2 study of the farnesyltransferase inhibitor tipifarnib (R115777) in patients with relapsed and refractory lymphomas

Thomas E Witzig; Hui Tang; Ivana N. M Micallef; Stephen M Ansell; Brian K Link; David J Inwards; Luis F Porrata; Patrick B Johnston; Joseph P Colgan; Svetomir N Markovic; Grzegorz S Nowakowski; Carrie A Thompson; Cristine Allmer; Matthew J Maurer; Mamta Gupta; George Weiner; Ray Hohl; Paul J Kurtin; Husheng Ding; David Loegering; Paula Schneider; Kevin Peterson; Thomas M Habermann; Scott H Kaufmann

doi:10.1182/blood-2011-02-334904

$Multi-institutional phase 2 study of the farnesyltransferase inhibitor tipifarnib (R115777) in patients with relapsed and refractory lymphomas$

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Multi-institutional phase 2 study of the farnesyltransferase inhibitor tipifarnib (R115777) in patients with relapsed and refractory lymphomas

Thomas E Witzig, Hui Tang, Ivana N. M Micallef, Stephen M Ansell, Brian K Link, David J Inwards, Luis F Porrata, Patrick B Johnston, Joseph P Colgan, Svetomir N Markovic, …

Blood, Vol.118(18), pp.4882-4889

11/03/2011

DOI: 10.1182/blood-2011-02-334904

PMCID: PMC3208296

PMID: 21725056

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Abstract

A phase 2 study of the oral farnesyltransferase inhibitor tipifarnib was conducted in 93 adult patients with relapsed or refractory lymphoma. Patients received tipifarnib 300 mg twice daily on days 1-21 of each 28-day cycle. The median number of prior therapies was 5 (range, 1-17). For the aggressive B-cell, indolent B-cell, and T-cell and Hodgkin lymphoma (HL/T) groups, the response rates were 17% (7/42), 7% (1/15), and 31% (11/36), respectively. Of the 19 responders, 7 were diffuse large B-cell non-Hodgkin lymphoma (NHL), 7 T-cell NHL, 1 follicular grade 2, and 4 HL. The median response duration for the 19 responders was 7.2 months (mean, 15.8 months; range, 1.8-62), and 5 patients in the HL/T group are still receiving treatment at 29-64+ months. The grade 3/4 toxicities observed were fatigue and reversible myelosuppression. Correlative studies suggest that Bim and Bcl-2 should be examined as potential predictors of response in future studies. These results indicate that tipifarnib has activity in lymphoma, particularly in heavily pretreated HL/T types, with little activity in follicular NHL. In view of its excellent toxicity profile and novel mechanism of action, further studies in combination with other agents appear warranted. This trial is registered at www.clinicaltrials.gov as #NCT00082888.

Lymphoid Neoplasia

Clinical Trials and Observations

Details

Title: Subtitle: Multi-institutional phase 2 study of the farnesyltransferase inhibitor tipifarnib (R115777) in patients with relapsed and refractory lymphomas
Creators: Thomas E Witzig - Division of Hematology, Department of Medicine and
Hui Tang - Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, MN
Ivana N. M Micallef - Division of Hematology, Department of Medicine and
Stephen M Ansell - Division of Hematology, Department of Medicine and
Brian K Link - University of Iowa, Iowa City, IA
David J Inwards - Division of Hematology, Department of Medicine and
Luis F Porrata - Division of Hematology, Department of Medicine and
Patrick B Johnston - Division of Hematology, Department of Medicine and
Joseph P Colgan - Division of Hematology, Department of Medicine and
Svetomir N Markovic - Division of Hematology, Department of Medicine and
Grzegorz S Nowakowski - Division of Hematology, Department of Medicine and
Carrie A Thompson - Division of Hematology, Department of Medicine and
Cristine Allmer - Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, MN
Matthew J Maurer - Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, MN
Mamta Gupta - Division of Hematology, Department of Medicine and
George Weiner - University of Iowa, Iowa City, IA
Ray Hohl - University of Iowa, Iowa City, IA
Paul J Kurtin - Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, MN; and
Husheng Ding - Division of Oncology Research, Department of Oncology, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, MN
David Loegering - Division of Oncology Research, Department of Oncology, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, MN
Paula Schneider - Division of Oncology Research, Department of Oncology, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, MN
Kevin Peterson - Division of Oncology Research, Department of Oncology, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, MN
Thomas M Habermann - Division of Hematology, Department of Medicine and
Scott H Kaufmann - Division of Hematology, Department of Medicine and
Resource Type: Journal article
Publication Details: Blood, Vol.118(18), pp.4882-4889
DOI: 10.1182/blood-2011-02-334904
PMID: 21725056
PMCID: PMC3208296
NLM abbreviation: Blood
ISSN: 0006-4971
eISSN: 1528-0020
Publisher: American Society of Hematology
Grant note: P50 CA97274; CA127433 / National Institutes of Health
Language: English
Date published: 11/03/2011
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
Record Identifier: 9984094542802771

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