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Pediatr Blood Cancer. 2015 Apr;62(4):629-36. doi: 10.1002/pbc.25342. Epub 2014 Dec 8.

Phase II/III trial of a pre-transplant farnesyl transferase inhibitor in juvenile myelomonocytic leukemia: a report from the Children's Oncology Group.

Author information

1
Department of Pediatrics, Helen Diller Comprehensive Cancer Center, University of California San Francisco School of Medicine and Benioff Children's Hospital, San Francisco, California.

Abstract

BACKGROUND:

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-cis retinoic acid (CRA) in combination with cytoreductive chemotherapy, and survival following HSCT in children with JMML.

PROCEDURE:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

13-cis retinoic acid; farnesyl transferase inhibitor; hematopoietic stem cell transplant; juvenile myelomonocytic leukemia; tipifarnib

PMID:
25704135
PMCID:
PMC4339233
DOI:
10.1002/pbc.25342
[Indexed for MEDLINE]
Free PMC Article

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