Annals of Hematology

, Volume 97, Issue 5, pp 763–772 | Cite as

A phase I–II study of plerixafor in combination with fludarabine, idarubicin, cytarabine, and G-CSF (PLERIFLAG regimen) for the treatment of patients with the first early-relapsed or refractory acute myeloid leukemia

  • David Martínez-Cuadrón
  • Blanca Boluda
  • Pilar Martínez
  • Juan Bergua
  • Rebeca Rodríguez-Veiga
  • Jordi Esteve
  • Susana Vives
  • Josefina Serrano
  • Belen Vidriales
  • Olga Salamero
  • Lourdes Cordón
  • Amparo Sempere
  • Ana Jiménez-Ubieto
  • Julio Prieto-Delgado
  • Marina Díaz-Beyá
  • Ana Garrido
  • Celina Benavente
  • José Antonio Pérez-Simón
  • Federico Moscardó
  • Miguel A. Sanz
  • Pau Montesinos
  • on behalf of the CETLAM and PETHEMA groups
Original Article

Abstract

Clinical outcomes of patients with acute myeloid leukemia (AML) showing the first primary refractory or early-relapsed disease remain very poor. The Programa Español de Tratamientos en Hematología (PETHEMA) group designed a phase I–II trial using FLAG-Ida (fludarabine, idarubicin, cytarabine, and G-CSF) plus high-dose intravenous plerixafor, a molecule inducing mobilization of blasts through the SDF-1α-CXCR4 axis blockade and potentially leading to chemosensitization of the leukemic cells. We aimed to establish a recommended phase 2 dose (RP2D) of plerixafor plus FLAG-Ida, as well as the efficacy and safety of this combination for early-relapsed (first complete remission (CR/CRi) < 12 months) or primary refractory AML. Between 2012 and 2015, 57 patients were enrolled, and 41 received the RP2D (median age 52 years [range, 18–64]). Among these patients, 20 (49%) achieved CR/CRi, and 3 (7%) died during induction. CR/CRi rate was 50% (13/26) among primary refractory and 47% (7/15) among early relapse. Overall, 25 patients (61%) were allografted. Median overall and disease-free survivals were 9.9 and 13 months, respectively. In summary, the combination of plerixafor plus FLAG-Ida resulted in a relatively high CR/CRi rate in adult patients with primary refractory or early relapsed AML, with an acceptable toxicity profile and induction mortality rate, bridging the majority of patients to allogeneic stem cell transplantation. ClinicalTrials.gov Identifier: NCT01435343

Keywords

Acute myeloid leukemia Plerixafor FLAG-Ida Resistance Relapse 

Notes

Acknowledgements

The authors thank Shirley Weiss, David Pellicer, María D. García, and Mar Benlloch for data collection and management and Rafael Andreu for helping in the interpretation of the inmunophenotype analyses.

Author contributions

F.M, P. Montesinos, and M.A.S conceived the study. D.M and P. Montesinos analyzed and interpreted the data; D.M, P. Montesinos, and M.A.S wrote the paper; D.M and P. Montesinos performed the statistical analyses; A.S and L.C performed and interpreted the inmunophenotype analyses; B.B, P. Martínez, J.B, R.R, J.E, S.V, J.S, B.V, O.S, A.J, J.P, M.D., A.G, C.B, and J.A.P included data of patients treated in their institutions. All authors reviewed the manuscript and contributed to the final draft.

Funding information

This work was partially financed with FEDER funds (CIBERONC (CB16/12/00284)). This work was supported by research funding from Sanofi-Genzyme.

Compliance with ethical standards

Informed consent was obtained from all patients. According to the Declaration of Helsinki, the trial was approved by the Research Ethics Board of each participating hospital.

Conflicts of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018
corrected publication February/2018

Authors and Affiliations

  • David Martínez-Cuadrón
    • 1
    • 2
  • Blanca Boluda
    • 1
  • Pilar Martínez
    • 3
  • Juan Bergua
    • 4
  • Rebeca Rodríguez-Veiga
    • 1
  • Jordi Esteve
    • 5
  • Susana Vives
    • 6
  • Josefina Serrano
    • 7
  • Belen Vidriales
    • 8
  • Olga Salamero
    • 9
  • Lourdes Cordón
    • 1
    • 2
  • Amparo Sempere
    • 1
    • 2
  • Ana Jiménez-Ubieto
    • 3
  • Julio Prieto-Delgado
    • 4
  • Marina Díaz-Beyá
    • 5
  • Ana Garrido
    • 10
  • Celina Benavente
    • 11
  • José Antonio Pérez-Simón
    • 12
  • Federico Moscardó
    • 1
  • Miguel A. Sanz
    • 1
    • 2
    • 13
  • Pau Montesinos
    • 1
    • 2
  • on behalf of the CETLAM and PETHEMA groups
  1. 1.Hematology DepartmentHospital Universitari i Politècnic, La FeValènciaSpain
  2. 2.CIBERONCInstituto Carlos IIIMadridSpain
  3. 3.Hospital 12 de OctubreMadridSpain
  4. 4.Hospital San Pedro de AlcántaraCáceresSpain
  5. 5.Hospital ClinicBarcelonaSpain
  6. 6.Hospital ICO-Universitari Germans Trias i PujolJosé Carreras Leukemia Research InstituteBadalonaSpain
  7. 7.Hospital Reina SofíaCórdobaSpain
  8. 8.Hospital Universitario de SalamancaSalamancaSpain
  9. 9.Hospital Universitari Vall d’HebronBarcelonaSpain
  10. 10.Hospital de la Santa Creu i Sant PauBarcelonaSpain
  11. 11.Hospital Clínico San CarlosMadridSpain
  12. 12.Hospital Universitario Virgen del RocíoSevillaSpain
  13. 13.Department of MedicineUniversity of ValenciaValenciaSpain

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