ActivePhase 4ACTRN12613000487718

High Dose Melphalan: A pilot study to evaluate pharmacokinetic-based dose determination in patients with multiple myeloma scheduled to undergo autologous stem cell transplantation

Sponsor

The Children's Hospital at Westmead

Enrollment

30 participants

Start Date

Apr 8, 2013

Study Type

Interventional

Conditions

Multiple Myeloma

Summary

The aim of this study is to evaluate whether a test dose of melphalan can be used successfully to target a desired exposure in patients with multiple myeloma scheduled to undergo autologous stem cell transplantation. Higher drug exposure is associated with improved disease control and survival post transplant. Who is it for? You may be eligible to join this study if you are a male or female of any age who is scheduled to receive single agent high dose melphalan and autologous stem cell rescue for multiple myeloma. Trial details All participants in this trial will receive a test dose of 20 mg/m2 melphalan 4 days prior to scheduled autologous stem cell transplantation. This drug will be administered intravenously (i.e. into the vein). A series of six blood samples will be collected after the test dose to allow pharmacokinetic assessment and predictions of exposure for the full dose. The treating clinician will decide the actual full dose to be administered. Whatever dose is given, blood sampling and pharmacokinetic assessment of the full dose will allow determination of whether the test dose exposure accurately predicts the full dose exposure. The test dose amount was increased from 10 mg/m2 in an amendment which was approved in December 2013 to improve the quality of the predictions.

Eligibility

Sex: Both males and females

Inclusion Criteria2

Patients of any age scheduled to receive single agent high dose melphalan and autologous stem cell rescue for multiple myeloma.
Written informed consent

Exclusion Criteria1

Those for whom written informed consent cannot be obtained.

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Interventions

On Day -4 prior to autologous stem cell transplantation, a test dose of 20 mg/m2 melphalan will be administered by intravenous infusion. A series of six blood samples will be collected after the end of the infusion. The plasma will be separated, frozen and sent for pharmacokinetic assessment, which will be completed by the end of Day -2 to allow calculation of the full melphalan dose, that will target a melphalan exposure level that chosen by the treating physician. On Day -1 the full melphalan dose will be administered, with repeat blood sampling to check whether the expected exposure was achieved. The treating physician will administer either the remaining 180 mg/m2 dose or another dose based on the test pharmacokinetic results targeting a melphalan exposure at or just above the median levels achieved in previous drug testing. The initial 10 mg/m2 test dose produced low melphalan concentration in two patients (close to the limit of detection of the assay), making it difficult to make predictions for full dose melphalan exposure. In December 2013, the test dose was therefore increased to 20 mg/m2 to improve the quality of the predictions.