Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000487718
Ethics application status
Approved
Date submitted
12/04/2013
Date registered
1/05/2013
Date last updated
2/05/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
High Dose Melphalan: A pilot study to evaluate pharmacokinetic-based dose determination in patients with multiple myeloma scheduled to undergo autologous stem cell transplantation
Scientific title
High Dose Melphalan: A pilot study to evaluate pharmacokinetic-based dose determination in patients with multiple myeloma scheduled to undergo autologous stem cell transplantation
Secondary ID [1] 282272 0
Nil
Universal Trial Number (UTN)
U1111-1141-6361
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 288807 0
Condition category
Condition code
Cancer 289164 289164 0 0
Myeloma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 286902 0
Treatment: Drugs
Comparator / control treatment
This is an uncontrolled pilot study
Control group
Uncontrolled

Outcomes
Primary outcome [1] 289272 0
To evaluate the feasibility of real-time pharmacokinetics in a multi-centre setting using a test dose of melphalan, followed by therapeutic drug monitoring (measuring the drug levels in repeated blood samples after it is infused) of a targeted dose of melphalan in patients with multiple myeloma
Timepoint [1] 289272 0
Blood sampling occurs at 5 min, 15 min, 30 min, 40 min, 1h 15 min and 2h 30 min after the end of the melphalan infusions for the test and full doses, which are administered between Day -4 and Day -1 before autologous stem cell transplantation.
Secondary outcome [1] 302139 0
To evaluate the influence of genetic factors on the pharmacokinetics of melphalan. An EDTA blood sample will be withdrawn prior to High dose melphalan for DNA extraction and evaluation of genetic polymorphisms in enzymes involved in drug metabolism and detoxification, such as the glutathione transferase enzymes.
Timepoint [1] 302139 0
Immediately prior to beginning the melphalan infusion for the test dose. It is not needed before the full dose.
Secondary outcome [2] 302552 0
To record transplant toxicity and engraftment parameters.
This includes
- Gastrointestinal toxicity, which will be graded daily using CTCAE v 4.03 criteria for the first 28 days post autologous stem cell transplant. Oral mucositis will also be graded daily using WHO criteria.
- Occurrence of any toxicity of Grade 3 or above (as defined in CTCAE version 4.03), including abnormal liver or renal function or cardiac or pulmonary toxicities.
- Occurrence of febrile neutropenia
- Recovery of neutrophils and platelets unsupported by blood transfusions
Timepoint [2] 302552 0
One month
Secondary outcome [3] 302553 0
To record disease outcomes in terms of Time to Progression and Overall survival
Timepoint [3] 302553 0
Up to 5 years post autologous stem cell transplant

Eligibility
Key inclusion criteria
1. Patients of any age scheduled to receive single agent high dose melphalan and autologous stem cell rescue for multiple myeloma.
2. Written informed consent
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Those for whom written informed consent cannot be obtained.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Not applicable.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
8/04/2013
Actual
8/04/2013
Date of last participant enrolment
Anticipated
1/01/2016
Actual
17/07/2015
Date of last data collection
Anticipated
17/07/2020
Actual
Sample size
Target
30
Accrual to date
Final
38
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 873 0
Concord Repatriation Hospital - Concord
Recruitment hospital [2] 874 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 875 0
Gosford Hospital - Gosford
Recruitment hospital [4] 876 0
St George Hospital - Kogarah
Recruitment hospital [5] 877 0
Royal Melbourne Hospital - Royal Park campus - Parkville
Recruitment hospital [6] 7907 0
Wollongong Hospital - Wollongong
Recruitment hospital [7] 7908 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 6684 0
2139 - Concord Repatriation Hospital
Recruitment postcode(s) [2] 6685 0
2050 - Camperdown
Recruitment postcode(s) [3] 6686 0
2250 - East Gosford
Recruitment postcode(s) [4] 6687 0
2217 - Kogarah
Recruitment postcode(s) [5] 15869 0
2520 - Wollongong
Recruitment postcode(s) [6] 15870 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 287078 0
Hospital
Name [1] 287078 0
KRI Bridging Grant at The Children's Hospital at Westmead
Country [1] 287078 0
Australia
Primary sponsor type
Hospital
Name
The Children's Hospital at Westmead
Address
Hawkesbury Rd.,
Westmead, NSW, 2145
Country
Australia
Secondary sponsor category [1] 285853 0
None
Name [1] 285853 0
Address [1] 285853 0
Country [1] 285853 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289093 0
Sydney Children's Hospitals Network Human Research Ethics Committee
Ethics committee address [1] 289093 0
Kids Research Institute,
The Children's Hospital at Westmead,
Hawkesbury Rd.
Westmead, NSW, 2145
Ethics committee country [1] 289093 0
Australia
Date submitted for ethics approval [1] 289093 0
Approval date [1] 289093 0
22/03/2013
Ethics approval number [1] 289093 0
12/SCHN/441

Summary
Brief 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.
Trial website
Trial related presentations / publications
Conference Proceedings:
1. Trotman J, Shaw PJ, Tiley C, Ramanathan S, Grigg A, Larsen S, Presgrave P, Kwan YL, Newman E, Estell J, Nath CE. Evaluation of pharmacokinetic-based dose predictions of high dose melphalan in patients with multiple myeloma. Inaugural National Myeloma Meeting, Victoria Aug 2016.
2. Trotman J, Shaw PJ, Tiley C, Ramanathan S, Grigg A, Larsen SR, Presgrave P, Yiu-Lam Kwan YL, Newman E, and Nath CE. Evaluation of Pharmacokinetic-based Dose Predictions of High Dose Melphalan in Patients with Multiple Myeloma. ASH poster presentation 2015. Blood 2015 126:4314.
Public notes

Contacts
Principal investigator
Name 39102 0
Dr Christa Nath
Address 39102 0
Department of Biochemistry,
The Children's Hospital at Westmead,
Hawkesbury Rd,
Westmead, NSW, 2145
Country 39102 0
Australia
Phone 39102 0
+61 (02) 98453287
Fax 39102 0
+61 (02) 98453332
Email 39102 0
[email protected]
Contact person for public queries
Name 39103 0
A/Prof Judith Trotman
Address 39103 0
Department of Haematology,
Concord Repatriation Hospital,
Hospital Rd,
Concord, NSW, 2139
Country 39103 0
Australia
Phone 39103 0
+61 (02) 97677243
Fax 39103 0
+61 (02) 97677650
Email 39103 0
[email protected]
Contact person for scientific queries
Name 39104 0
Dr Christa Nath
Address 39104 0
Department of Biochemistry,
The Children's Hospital at Westmead,
Hawkesbury Rd,
Westmead, NSW, 2145
Country 39104 0
Australia
Phone 39104 0
+61 (02) 98453287
Fax 39104 0
+61 (02) 98453332
Email 39104 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23265Informed consent form    Information sheets and consent forms were shared w... [More Details]

Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseChallenges associated with test dose pharmacokinetic predictions of high dose melphalan exposure in patients with multiple myeloma.2022https://dx.doi.org/10.1007/s00228-022-03396-x
N.B. These documents automatically identified may not have been verified by the study sponsor.