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Plasma Cell Disorders

Phase IIa cross-over study of propylene glycol-free melphalan (LGD-353) and alkeran in multiple myeloma autologous transplantation

Bone Marrow Transplantation volume 49, pages 1042–1045 (2014)Cite this article

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Abstract

Propylene Glycol-Free melphalan HCL for Injection (PGF-Mel) is a new formulation that incorporates Captisol, a specially modified cyclodextrin, to improve melphalan stability. In this phase IIa, open-label, randomized, cross-over design bioequivalence study, the pharmacokinetics of PGF-Mel were compared with the marketed formulation of melphalan, or Alkeran. Patients received half of the total dose of melphalan in the form of Alkeran and the other half in the form of PGF-Mel in an alternating manner. The pharmacokinetic measures were determined using WinNonlin 6.2 and bioequivalence was assessed using log-transformed systemic exposure parameters. Twenty-four patients, 11 females and 13 males, were enrolled between 4 February 2010 and 16 May 2011 at The University of Kansas Medical Center and The University of Kansas Cancer Center. The median age of enrolled subjects was 58 years (range: 48–65). All patients achieved myeloablation 3 days post autologous graft followed by successful neutrophil engraftment with a median of 11 days after transplant. Pharmacokinetic analysis showed that PGF-Mel was bioequivalent with Alkeran and also revealed that maximum plasma concentration (Cmax) and area under the plasma concentration−time curve (AUC) were higher (~10%) after PGF-Mel administration. In conclusion, PGF-Mel is considered bioequivalent to Alkeran while also demonstrating a marginally higher systemic drug exposure.

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Acknowledgements

We would like to thank all of the patients who participated in this effort. Special thanks to the study coordinator Kelly Daniels and the data manager Karen Wolfe for their help in conducting the study. We would like to thank Yu-Hui (Ann) Fu and team at the KCAS Bioanalytical Services for plasma sample management and for melphalan plasma assays. We would also like to thank Kim Frieze (Beckloff Associates, Inc) and Gilad Gordon, MD (Medical Monitor) for reviewing the data and the final manuscript. OSA is a recipient of a research career award by the Office of Scholarly, Academic & Research Mentoring (OSARM) at his home institution, the University of Kansas Medical Center. Ligand Pharmaceuticals Incorporated (sponsor) received support from the Kansas Biosciences Authority for this collaboration with the University of Kansas Medical Center.

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Authors and Affiliations

  1. Division of Hematology/Oncology, and Department of Internal Medicine, Blood and Marrow Transplant Program, University of Kansas Medical Center, Kansas City, KS, USA

    O S Aljitawi, S Ganguly, S H Abhyankar & J P McGuirk

  2. Clinipace Worldwide, Overland Park, KS, USA

    M Ferree & R Marks

  3. Ligand Pharmaceuticals Incorporated, Lawrence, KS, USA,

    J D Pipkin

Authors
  1. O S Aljitawi
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  2. S Ganguly
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  3. S H Abhyankar
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  4. M Ferree
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  6. J D Pipkin
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  7. J P McGuirk
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Correspondence to O S Aljitawi.

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Competing interests

JDP is employed by the sponsoring company Ligand Pharmaceuticals Incorporated, Lawrence, KS, USA, the remaining authors declare no conflict of interest.

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Aljitawi, O., Ganguly, S., Abhyankar, S. et al. Phase IIa cross-over study of propylene glycol-free melphalan (LGD-353) and alkeran in multiple myeloma autologous transplantation. Bone Marrow Transplant 49, 1042–1045 (2014). https://doi.org/10.1038/bmt.2014.120

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