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International Journal of Hematology

, Volume 99, Issue 3, pp 272–278 | Cite as

Phase I study of cladribine, cytarabine, granulocyte colony stimulating factor (CLAG regimen) and midostaurin and all-trans retinoic acid in relapsed/refractory AML

  • Giridharan Ramsingh
  • Peter Westervelt
  • Ali McBride
  • Keith Stockerl-Goldstein
  • Ravi Vij
  • Mark Fiala
  • Geoffrey Uy
  • Amanda Cashen
  • John F. DiPersio
  • Camille N. Abboud
Original Article

Abstract

We conducted a phase I study using midostaurin (25 or 50 mg orally twice daily), all-trans retinoic acid (ATRA) and CLAG chemotherapy to target multiple pathways in relapsed/refractory AML. 10 patients received the combination and no dose-limiting toxicities were observed. Two patients (22 %) achieved complete remission and 1 patient (11 %) achieved complete remission with incomplete count recovery. Pharmacokinetic data showed that the 25 mg dosing of midostaurin achieved therapeutic levels with no significant interaction between midostaurin and ATRA. With evidence of activity of ATRA in NPM1-mutated AML and midostaurin in FLT3-ITD AML, this combination warrants further investigation.

Keywords

AML Midostaurin ATRA Phase I Targeted therapy CLAG 

Abbreviations

AML

Acute myelogenous leukemia

CLAG

Cladribine 5 mg/m2 given intravenously on days 2–6, Ara-C 2 g/m2 given intravenously on days 2–6, G-CSF 300 μg given subcutaneously on days 1–6

ATRA

All-trans retinoic acid

ICTS

Institute for Clinical and Translational Science

Ara-C

Cytarabine

G-CSF

Granulocyte colony stimulating factor

MDS

Myelodysplastic syndrome

CR

Complete remission

PR

Partial remission

CRi

Complete remission with incomplete count recovery

MTD

Maximum tolerated dose

DLT

Dose-limiting toxicity

Notes

Conflict of interest

C.N.A. obtained research support for this study from Novartis and serves in the advisory board for Novartis.

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Copyright information

© The Japanese Society of Hematology 2014

Authors and Affiliations

  • Giridharan Ramsingh
    • 1
  • Peter Westervelt
    • 2
  • Ali McBride
    • 3
    • 4
  • Keith Stockerl-Goldstein
    • 2
  • Ravi Vij
    • 2
  • Mark Fiala
    • 2
  • Geoffrey Uy
    • 2
  • Amanda Cashen
    • 2
  • John F. DiPersio
    • 2
  • Camille N. Abboud
    • 2
  1. 1.Jane Anne Nohl Division of Hematology, Department of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  2. 2.Section BMT and Leukemia, Division of OncologyWashington University School of MedicineSt LouisUSA
  3. 3.Department of PharmacyThe University of Arizona Cancer CenterTucsonUSA
  4. 4.The University of Arizona College of PharmacyTucsonUSA

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