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, Raymond Hohl, Paul J. Kurtin, Husheng Ding, David Loegering & 4 others Paula Schneider, Kevin Peterson, Thomas M. Habermann, Scott H. Kaufmann

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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.

Original languageEnglish (US)
Pages (from-to)4882-4889
Number of pages8
JournalBlood
Volume118
Issue number18
DOIs
StatePublished - Nov 3 2011

Fingerprint

tipifarnib
Farnesyltranstransferase
Refractory materials
Non-Hodgkin's Lymphoma
Lymphoma
T-cells
T-Cell Lymphoma
Cells
Toxicity
B-Lymphocytes
Follicular Lymphoma
B-Cell Lymphoma
Hodgkin Disease
Fatigue
Fatigue of materials
Therapeutics

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Witzig, T. E., Tang, H., Micallef, I. N. M., Ansell, S. M., Link, B. K., Inwards, D. J., ... Kaufmann, S. H. (2011). Multi-institutional phase 2 study of the farnesyltransferase inhibitor tipifarnib (R115777) in patients with relapsed and refractory lymphomas. Blood, 118(18), 4882-4889. https://doi.org/10.1182/blood-2011-02-334904
Witzig, Thomas E. ; Tang, Hui ; Micallef, Ivana N.M. ; Ansell, Stephen M. ; Link, Brian K. ; Inwards, David J. ; Porrata, Luis F. ; Johnston, Patrick B. ; Colgan, Joseph P. ; Markovic, Svetomir N. ; Nowakowski, Grzegorz S. ; Thompson, Carrie A. ; Allmer, Cristine ; Maurer, Matthew J. ; Gupta, Mamta ; Weiner, George ; Hohl, Raymond ; Kurtin, Paul J. ; Ding, Husheng ; Loegering, David ; Schneider, Paula ; Peterson, Kevin ; Habermann, Thomas M. ; Kaufmann, Scott H. / Multi-institutional phase 2 study of the farnesyltransferase inhibitor tipifarnib (R115777) in patients with relapsed and refractory lymphomas. In: Blood. 2011 ; Vol. 118, No. 18. pp. 4882-4889.
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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.",
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Witzig, TE, Tang, H, Micallef, INM, Ansell, SM, Link, BK, Inwards, DJ, Porrata, LF, Johnston, PB, Colgan, JP, Markovic, SN, Nowakowski, GS, Thompson, CA, Allmer, C, Maurer, MJ, Gupta, M, Weiner, G, Hohl, R, Kurtin, PJ, Ding, H, Loegering, D, Schneider, P, Peterson, K, Habermann, TM & Kaufmann, SH 2011, 'Multi-institutional phase 2 study of the farnesyltransferase inhibitor tipifarnib (R115777) in patients with relapsed and refractory lymphomas', Blood, vol. 118, no. 18, pp. 4882-4889. https://doi.org/10.1182/blood-2011-02-334904

Multi-institutional phase 2 study of the farnesyltransferase inhibitor tipifarnib (R115777) in patients with relapsed and refractory lymphomas. / Witzig, Thomas E.; Tang, Hui; Micallef, Ivana N.M.; Ansell, Stephen M.; Link, Brian K.; Inwards, David J.; Porrata, Luis F.; Johnston, Patrick B.; Colgan, Joseph P.; Markovic, Svetomir N.; Nowakowski, Grzegorz S.; Thompson, Carrie A.; Allmer, Cristine; Maurer, Matthew J.; Gupta, Mamta; Weiner, George; Hohl, Raymond; Kurtin, Paul J.; Ding, Husheng; Loegering, David; Schneider, Paula; Peterson, Kevin; Habermann, Thomas M.; Kaufmann, Scott H.

In: Blood, Vol. 118, No. 18, 03.11.2011, p. 4882-4889.

Research output: Contribution to journalArticle

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T1 - Multi-institutional phase 2 study of the farnesyltransferase inhibitor tipifarnib (R115777) in patients with relapsed and refractory lymphomas

AU - Witzig, Thomas E.

AU - Tang, Hui

AU - Micallef, Ivana N.M.

AU - Ansell, Stephen M.

AU - Link, Brian K.

AU - Inwards, David J.

AU - Porrata, Luis F.

AU - Johnston, Patrick B.

AU - Colgan, Joseph P.

AU - Markovic, Svetomir N.

AU - Nowakowski, Grzegorz S.

AU - Thompson, Carrie A.

AU - Allmer, Cristine

AU - Maurer, Matthew J.

AU - Gupta, Mamta

AU - Weiner, George

AU - Hohl, Raymond

AU - Kurtin, Paul J.

AU - Ding, Husheng

AU - Loegering, David

AU - Schneider, Paula

AU - Peterson, Kevin

AU - Habermann, Thomas M.

AU - Kaufmann, Scott H.

PY - 2011/11/3

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N2 - 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.

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