Phase II/III trial of a pre‐transplant farnesyl transferase inhibitor in juvenile myelomonocytic leukemia: A report from the Children's Oncology Group. Issue 4 (8th December 2014)

• Record Type: Journal Article
• Authors: Stieglitz, Elliot; Ward, Ashley F.; Gerbing, Robert B.; Alonzo, Todd A.; Arceci, Robert J.; Liu, Y. Lucy; Emanuel, Peter D.; Widemann, Brigitte C.; Cheng, Jennifer W.; Jayaprakash, Nalini; Balis, Frank M.; Castleberry, Robert P.; Bunin, Nancy J.; Loh, Mignon L.; Cooper, Todd M.
• Is Part Of: Pediatric blood & cancer. Volume 62:Issue 4(2015:Apr.)
• Page Start: 629
• Page End: 636
• Publication Date: 2014-12-08
• Subjects: Tumors in children -- Periodicals; Blood -- Diseases -- Periodicals; Cancer in children -- Periodicals; 618.92
• DOI: 10.1002/pbc.25342
• Languages: English
• ISSNs: 1545-5009

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="pbc25342-sec-0001" sec-type="section"> <title>Background</title> <p>Juvenile myelomonocytic leukemia (JMML) is not durably responsive to chemotherapy, and approximately 50% of patients relapse after hematopoietic stem cell transplant (HSCT). Here we report the activity and acute toxicity of the farnesyl transferase inhibitor tipifarnib, the response rate to 13‐<italic>cis</italic> retinoic acid (CRA) in combination with cytoreductive chemotherapy, and survival following HSCT in children with JMML.</p> </sec> <sec id="pbc25342-sec-0002" sec-type="section"> <title>Procedure</title> <p>Eighty‐five patients with newly diagnosed JMML were enrolled on AAML0122 between 2001 and 2006. Forty‐seven consented to receive tipifarnib in a phase II window before proceeding to a phase III trial of CRA in combination with fludarabine and cytarabine followed by HSCT and maintenance CRA. Thirty‐eight patients enrolled only in the phase III trial.</p> </sec> <sec id="pbc25342-sec-0003" sec-type="section"> <title>Results</title> <p>Overall response rate was 51% after tipifarnib and 68% after fludarabine/cytarabine/CRA. Tipifarnib did not increase pre‐transplant toxicities. Forty‐six percent of the 44 patients who received protocol compliant HSCT relapsed. Five‐year overall survival was 55 ± 11% and event‐free survival was 41 ± 11%, with no significant difference between patients who did or did not receive tipifarnib.</p> </sec> <sec id="pbc25342-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Administration of tipifarnib in the window setting followed by HSCT in patients with newly diagnosed JMML was safe and yielded a 51% initial response rate as a single agent, but failed to reduce relapse rates or improve long‐term overall survival. Pediatr Blood Cancer 2015;62:629–636. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>