Phase II Study of Dasatinib in Relapsed or Refractory Chronic Lymphocytic Leukemia

[Guest guest]

BlankPhase II Study of Dasatinib in Relapsed or Refractory Chronic Lymphocytic

Leukemia

1.. Philip C. Amrein1,5,

2.. Eyal C. Attar1,5,

3.. Tak Takvorian1,5,

4.. Ephraim P. Hochberg1,5,

5.. K. Ballen1,5,

6.. Kathleen M. Leahy1,

7.. C. Fisher2,5,

8.. Ann S. LaCasce2,5,

9.. D. sen2,5,

10.. Philippe Armand2,5,

11.. P. Hasserjian4,

12.. Lillian Werner3,

13.. Donna Neuberg3, and

14.. R. Brown2,5

+ Author Affiliations

1.. Authors' Affiliations:1Massachusetts General Hospital Cancer Center;

2Medical Oncology and 3Department of Biostatistics, Dana-Farber Cancer

Institute; 4Department of Pathology, Massachusetts General Hospital; and

5Medicine, Harvard Medical School, Boston, MA

1.. Corresponding Author:

Philip C. Amrein, Yawkey 7-942, Massachusetts General Hospital, Boston, MA

02114. Phone: 617-726-8748; Fax: 617-643-1915; E-mail: pamrein@...

Abstract

Purpose: Chronic lymphocytic leukemia (CLL) cells treated with dasatinib in

vitro undergo apoptosis via inhibition of Lyn kinase. Thus, in this study we

tested the activity of dasatinib in patients with relapsed CLL.

Experimental Design: Patients were eligible for this phase II trial if they had

documented CLL/SLL and had failed at least 1 prior therapy with a

fludarabine-containing regimen and if they required therapy according to NCI-WG

criteria. The starting dose of dasatinib was 140 mg daily.

Results: Fifteen patients were enrolled, with a median age of 59 and a median of

3 prior regimens. All patients had received fludarabine, and 5 were

fludarabine-refractory. Eleven of the 15 (73%) had high risk del(11q) or

del(17p) cytogenetics. The primary toxicity was myelosuppression, with grade 3

or 4 neutropenia and thrombocytopenia in 10 and 6 patients, respectively.

Partial responses by NCI-WG criteria were achieved in 3 of the 15 patients (20%;

90% CI: 6–44). Among the remaining 12 patients, 5 had nodal responses by

physical exam, and 1 patient had a nodal and lymphocyte response but with severe

myelosuppression. Pharmacodynamic studies indicated apoptosis in peripheral

blood CLL cells within 3 to 6 hours after dasatinib administration, associated

with downregulation of Syk (spleen tyrosine kinase) mRNA.

Conclusions: Dasatinib as a single agent has activity in relapsed and refractory

CLL. Clin Cancer Res; 17(9); 2977–86. ©2011 AACR.