A phase I study of intermediate dose cytarabine in combination with lenalidomide in relapsed/refractory acute myeloid leukemia

Elizabeth A. Griffiths; William E. Brady; Wei Tan; Carlos E. Vigil; James E. Thompson; Laurie A. Ford; Noelle M. Dickey; Heather L. Bashaw; Jill Sperrazza; Meir Wetzler; Eunice S. Wang

doi:10.1016/j.leukres.2016.02.003

A phase I study of intermediate dose cytarabine in combination with lenalidomide in relapsed/refractory acute myeloid leukemia

Elizabeth A. Griffiths^*, William E. Brady, Wei Tan, Carlos E. Vigil, James E. Thompson, Laurie A. Ford, Noelle M. Dickey, Heather L. Bashaw, Jill Sperrazza, Meir Wetzler, Eunice S. Wang

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

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Abstract

Relapsed/refractory (r/r) Acute Myeloid Leukemia (AML) remains a therapeutic challenge. Cytarabine arabinoside (AraC) forms the backbone of most regimens, with complete responses (CR) ranging from 17 to 20%. Lenalidomide (Len) is approved by the FDA for multiple myeloma and myelodysplasia and has demonstrated activity in AML. We developed a phase I study to evaluate the safety and tolerability of Len in combination with intermediate dose AraC (1.5 g/m²/day given on days 1-5) in adults with r/r AML. The maximally tolerated dose for this combination was 10 mg daily on days 6-26 of a 28 day cycle. Dose de-escalation from 25 mg was required due to rash, liver function abnormalities, and hypokalemia. Of 32 evaluable patients, five achieved CR (16%), 5CRi (16%) and 3 had hematological improvements for an overall response rate of 41% (13/32). Median overall survival (95% confidence interval) for patients treated on study was 5.8 (2.5-10.6) months and disease free survival was 3.4 (2.3-6.2) months. This single institute phase I trial of Len and intermediate dose AraC was associated with marked skin and other toxicities. At the dose and schedule tested, this combination did not appear to result in improved CR over single agent AraC for r/r AML.

Original language	English (US)
Pages (from-to)	44-48
Number of pages	5
Journal	Leukemia Research
Volume	43
DOIs	https://doi.org/10.1016/j.leukres.2016.02.003
State	Published - Apr 1 2016

Funding

The authors would like to thank the patients who participated in this and all clinical trials, without whom no improvement in therapy would be possible. This study was an investigator initiated clinical trial sponsored by Celgene, Inc . The study investigators were supported partially by grants from the National Cancer Institute Grant CA16056 (EAG, MW), the Szefel Foundation (MW), the Leonard S. LoVullo Endowment for Leukemia Research (MW), the Nancy C. Cully Endowment for Leukemia Research (MW), the Babcock Family Endowment (MW), the Heidi Leukemia Research Fund (MW), and the Roswell Park Alliance Foundation (EAG). The study used shared resources supported by RPCI’s Cancer Center Support Grant from the NCI (P30CA016056). EAG discloses honoraria from Celgene Inc. and Alexion Pharmaceuticals, advisory board contributions to Ariad Pharmaceuticals and research funding and honoraria from Astex Pharmaceuticals . MW received honoraria and research funding from Teva Pharmacueticals .

Keywords

Acute myeloid leukemia
Clinical trial
Cytarabine
Lenalidomide
Phase I
Relapse/refractory AML

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.leukres.2016.02.003

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title = "A phase I study of intermediate dose cytarabine in combination with lenalidomide in relapsed/refractory acute myeloid leukemia",

abstract = "Relapsed/refractory (r/r) Acute Myeloid Leukemia (AML) remains a therapeutic challenge. Cytarabine arabinoside (AraC) forms the backbone of most regimens, with complete responses (CR) ranging from 17 to 20%. Lenalidomide (Len) is approved by the FDA for multiple myeloma and myelodysplasia and has demonstrated activity in AML. We developed a phase I study to evaluate the safety and tolerability of Len in combination with intermediate dose AraC (1.5 g/m2/day given on days 1-5) in adults with r/r AML. The maximally tolerated dose for this combination was 10 mg daily on days 6-26 of a 28 day cycle. Dose de-escalation from 25 mg was required due to rash, liver function abnormalities, and hypokalemia. Of 32 evaluable patients, five achieved CR (16%), 5CRi (16%) and 3 had hematological improvements for an overall response rate of 41% (13/32). Median overall survival (95% confidence interval) for patients treated on study was 5.8 (2.5-10.6) months and disease free survival was 3.4 (2.3-6.2) months. This single institute phase I trial of Len and intermediate dose AraC was associated with marked skin and other toxicities. At the dose and schedule tested, this combination did not appear to result in improved CR over single agent AraC for r/r AML.",

keywords = "Acute myeloid leukemia, Clinical trial, Cytarabine, Lenalidomide, Phase I, Relapse/refractory AML",

author = "Griffiths, {Elizabeth A.} and Brady, {William E.} and Wei Tan and Vigil, {Carlos E.} and Thompson, {James E.} and Ford, {Laurie A.} and Dickey, {Noelle M.} and {L. Bashaw}, Heather and Jill Sperrazza and Meir Wetzler and Wang, {Eunice S.}",

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AU - Griffiths, Elizabeth A.

AU - Brady, William E.

AU - Tan, Wei

AU - Vigil, Carlos E.

AU - Thompson, James E.

AU - Ford, Laurie A.

AU - Dickey, Noelle M.

AU - L. Bashaw, Heather

AU - Sperrazza, Jill

AU - Wetzler, Meir

AU - Wang, Eunice S.

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N2 - Relapsed/refractory (r/r) Acute Myeloid Leukemia (AML) remains a therapeutic challenge. Cytarabine arabinoside (AraC) forms the backbone of most regimens, with complete responses (CR) ranging from 17 to 20%. Lenalidomide (Len) is approved by the FDA for multiple myeloma and myelodysplasia and has demonstrated activity in AML. We developed a phase I study to evaluate the safety and tolerability of Len in combination with intermediate dose AraC (1.5 g/m2/day given on days 1-5) in adults with r/r AML. The maximally tolerated dose for this combination was 10 mg daily on days 6-26 of a 28 day cycle. Dose de-escalation from 25 mg was required due to rash, liver function abnormalities, and hypokalemia. Of 32 evaluable patients, five achieved CR (16%), 5CRi (16%) and 3 had hematological improvements for an overall response rate of 41% (13/32). Median overall survival (95% confidence interval) for patients treated on study was 5.8 (2.5-10.6) months and disease free survival was 3.4 (2.3-6.2) months. This single institute phase I trial of Len and intermediate dose AraC was associated with marked skin and other toxicities. At the dose and schedule tested, this combination did not appear to result in improved CR over single agent AraC for r/r AML.

AB - Relapsed/refractory (r/r) Acute Myeloid Leukemia (AML) remains a therapeutic challenge. Cytarabine arabinoside (AraC) forms the backbone of most regimens, with complete responses (CR) ranging from 17 to 20%. Lenalidomide (Len) is approved by the FDA for multiple myeloma and myelodysplasia and has demonstrated activity in AML. We developed a phase I study to evaluate the safety and tolerability of Len in combination with intermediate dose AraC (1.5 g/m2/day given on days 1-5) in adults with r/r AML. The maximally tolerated dose for this combination was 10 mg daily on days 6-26 of a 28 day cycle. Dose de-escalation from 25 mg was required due to rash, liver function abnormalities, and hypokalemia. Of 32 evaluable patients, five achieved CR (16%), 5CRi (16%) and 3 had hematological improvements for an overall response rate of 41% (13/32). Median overall survival (95% confidence interval) for patients treated on study was 5.8 (2.5-10.6) months and disease free survival was 3.4 (2.3-6.2) months. This single institute phase I trial of Len and intermediate dose AraC was associated with marked skin and other toxicities. At the dose and schedule tested, this combination did not appear to result in improved CR over single agent AraC for r/r AML.

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KW - Clinical trial

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KW - Phase I

KW - Relapse/refractory AML

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ER -

A phase I study of intermediate dose cytarabine in combination with lenalidomide in relapsed/refractory acute myeloid leukemia

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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