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Trial registered on ANZCTR


Registration number
ACTRN12606000231549
Ethics application status
Approved
Date submitted
17/05/2006
Date registered
7/06/2006
Date last updated
3/05/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Pharmacokinetics and pharmacodynamics of high dose melphalan in myeloma patients undergoing an autograft.
Scientific title
Using blood melphalan concentrations to reduce toxicity and improve outcome in myeloma autograft recipients
Secondary ID [1] 268 0
Cancer Trials NSW: PK-10-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple myeloma 1209 0
Condition category
Condition code
Cancer 1294 1294 0 0
Myeloma

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This is a multi-institutional study in which a single high dose of melphalan will be administered intravenously over 30 minutes and plasma melphalan concentrations will be measured following the dose to see whether there is a relationship with disease response or toxicity post transplant.. The standard melphalan dose is 200 mg/m2, but some patients will have reduced doses due to renal dysfunction or obesity and this will be according to existing protocols at each participating institution. This is an observational study with no control group.
Intervention code [1] 1033 0
Treatment: Drugs
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 1763 0
1. We will be establishing the pharmacokinetics of melphalan in a large population of patients with myeloma. Total exposure (or area-under-the-concentration-versus-time curve, AUC) and other pharmacokinetic parameters will be determined for each individual using the blood concentrations.
Timepoint [1] 1763 0
Measured after a single dose.
Primary outcome [2] 1764 0
2. Data about the patient (e.g. weight, height, surface area, renal function, laboratory values, disease stage and other details, prior chemotherapy) to allow an assessment of the factors that may contribute to the variability in melphalan pharmacokinetic parameters and transplant outcome.
Timepoint [2] 1764 0
Collected prior to the melphalan dose and autologous transplant, on study enrolment.
Primary outcome [3] 1765 0
3. Transplant related toxicity including mucositis, gastrointestinal toxicity, haematological toxicity, and other toxicities
Timepoint [3] 1765 0
Followed for up to 4 weeks post the melphalan dose and autologous transplant.
Primary outcome [4] 1766 0
4. Disease response and survival
Timepoint [4] 1766 0
Followed for up to 2 years post transplant.
Primary outcome [5] 1767 0
5. Statistical methods will be used to identify a target AUC range that is associated with a good outcome with acceptable toxicity.
Timepoint [5] 1767 0
Analysis will be performed when data on all 140 patients has been collected. This will be approximately 2 years after the transplant date of the last patient recruited into the study.
Primary outcome [6] 1768 0
6. The population pharmacokinetic model can then be used to design a dosing schedule the will aim to provide patients, including those who are heavy or who have renal impairment, with an AUC within the target range to provide the optimal outcome.
Timepoint [6] 1768 0
When data from 60 patients has been collected. This analysis is currently being performed.
Secondary outcome [1] 3115 0
Nil
Timepoint [1] 3115 0
Nil

Eligibility
Key inclusion criteria
All myeloma patients scheduled to receive high dose melphalan followed by an autologous transplant.
Minimum age
18 Years
Maximum age
Not stated
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
The only patients that will be exluded from the study are those unable to give informed consent.

Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 356 0
61

Funding & Sponsors
Funding source category [1] 1420 0
Government body
Name [1] 1420 0
NHMRC project grant 396702
Address [1] 1420 0
MDP 70,
GPO Box 9848
Canberra, ACT, 2601
Country [1] 1420 0
Australia
Primary sponsor type
Hospital
Name
The Childrens Hospital at Westmead
Address
Hawkesbury Rd. Westmead, NSW, 2145
Country
Australia
Secondary sponsor category [1] 1248 0
Hospital
Name [1] 1248 0
Concord Hospital
Address [1] 1248 0
Hospital Rd.
Concord, NSW, 2139
Country [1] 1248 0
Australia
Secondary sponsor category [2] 2304 0
Other Collaborative groups
Name [2] 2304 0
Cancer Trials NSW
Address [2] 2304 0
153 Dowling St.
Woolloomooloo,
NSW, 2011
Country [2] 2304 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 2781 0
Concord Hospital
Ethics committee address [1] 2781 0
Hospital Rd.
Concord, NSW, 2139
Ethics committee country [1] 2781 0
Australia
Date submitted for ethics approval [1] 2781 0
Approval date [1] 2781 0
16/03/2004
Ethics approval number [1] 2781 0
CH62/6/2004-016
Ethics committee name [2] 2782 0
Wollongong Hospital
Ethics committee address [2] 2782 0
Loftus St.
Wollongong,
NSW, 2500
Ethics committee country [2] 2782 0
Australia
Date submitted for ethics approval [2] 2782 0
Approval date [2] 2782 0
05/04/2005
Ethics approval number [2] 2782 0
HE05/075
Ethics committee name [3] 2783 0
Royal Prince Alfred Hospital
Ethics committee address [3] 2783 0
Missenden Rd.
Camperdown, NSW, 2050
Ethics committee country [3] 2783 0
Australia
Date submitted for ethics approval [3] 2783 0
Approval date [3] 2783 0
02/06/2004
Ethics approval number [3] 2783 0
X04-0105
Ethics committee name [4] 2784 0
St George Hospital
Ethics committee address [4] 2784 0
South St.
Kogarah,
NSW, 2217
Ethics committee country [4] 2784 0
Australia
Date submitted for ethics approval [4] 2784 0
Approval date [4] 2784 0
08/02/2005
Ethics approval number [4] 2784 0
05/06
Ethics committee name [5] 2785 0
Westmead Hospital
Ethics committee address [5] 2785 0
Hawkesbury Rd.
Westmead, NSW, 2145
Ethics committee country [5] 2785 0
Australia
Date submitted for ethics approval [5] 2785 0
Approval date [5] 2785 0
09/06/2004
Ethics approval number [5] 2785 0
2004/4/4.13(1831)
Ethics committee name [6] 2786 0
Gosford Hospital
Ethics committee address [6] 2786 0
Cnr Holden Street and Racecourse Road, GOSFORD NSW 2250
Ethics committee country [6] 2786 0
Australia
Date submitted for ethics approval [6] 2786 0
Approval date [6] 2786 0
19/01/2006
Ethics approval number [6] 2786 0
05/65

Summary
Brief summary
This study is measuring blood levels of the medication melphalan to improve the way to adjust the dose for people with myeloma.
Who is it for?
You can join the this study if you have myeloma (a cancer which affects plasma cells in the bone marrow) and are undergoing a bone marrow transplant.
Trial details
Participants will receive the drug melphalan and will be tested to see how their body breaks down and gets rid of the medication.
This study does not replace other studies, but simply investigates key medication widely used in the treatment of myeloma. Participants will be followed for several years after the study to monitor their health.
This study will help to define the best way to adjust doses of the drug melphalan, a key medication in helping to control myeloma. Too much causes toxicity and too little risks the disease being more likely to return.
Trial website
Trial related presentations / publications
SCIENTIFIC PUBLICATIONS
1. Nath CE, Trotman J, Tiley C, Presgrave P, Joshua D, Kerridge I, Kwan YL, Gurney H, McLachlan A, Earl J, Nivison-Smith I, Zeng L, Shaw PJ. High melphalan exposure is associated with improved overall survival in myeloma patients receiving high dose melphalan and autologous transplantation. Br J. Clin Pharmacol. 2016, 82: 149-159.
2. Nath CE, Shaw PJ, Trotman J, Zeng L, Duffull SB, Hegarty G, McLachlan AJ, Gurney H, Kerridge I, Kwan Y, Presgrave P, Tiley C, Joshua D, Earl J. (2010) Population pharmacokinetics of melphalan in patients with multiple myeloma undergoing high dose therapy. British Journal of Clinical Pharmacology. 69: 484 – 497.
3. Nath CE, Zeng L, Eslick A, Trotman J and Earl J. (2008) An isocratic UV HPLC Assay for the determination of total and free melphalan concentrations in human plasma. Acta Chromatographica. 20(3); 383 – 398.
4. Nath CE, Shaw PJ, Trotman J and Zeng L. (2007) Pharmacokinetics of melphalan in myeloma patients undergoing an autograft. Bone Marrow Transplant. 40: 707 – 708.

Conference Presentations

1. Shaw PJ, Nath CE, Nivison-Smith I, Joshua DE, Kerridge IH, Presgrave P, Tiley CR, Kwan YL and Trotman J. Higher Melphalan exposure is associated with improved overall survival for myeloma patients undergoing autologous transplant. Biol Blood Marrow Transplant (2012) : 18 (2) Suppl 2 Pages: S207 Meeting Abstract: 13
2. PJ Shaw, CE Nath, J Trotman, H Gurney, L Zeng, Y Kwan, P Presgrave, C Tiley, D Joshua, I Kerridge, AJ McLachlan, JW Earl. Actual weight to calculate surface area provides the best estimate for AUC in myeloma. ASBMT Feb 2010. Biol Blood Marrow Transplant 2010; 16(2): S180. DOI: 10.1016/j.bbmt.2009.12.088.
3. SB Duffull, G Hegarty, CE Nath, PJ Shaw and J Trotman. Evaluation of an optimal design for examining melphalan pharmacokinetics in patients with multiple myeloma. PAGANZ Feb 2010.
4. CE Nath, PJ Shaw , J Trotman , L Zeng, S Duffull, AJ McLachlan, H Gurney , Y Kwan, P Presgrave, C Tiley, D Joshua, I Kerridge and J Earl. Population pharmacokinetics of melphalan in patients with multiple myeloma. PAGANZ Feb 2010.
5. CE Nath, PJ Shaw, J Trotman, L Zeng, S Duffull, AJ McLachlan, H Gurney, I Kerridge, Y Kwan, P Presgrave, C Tiley, D Joshua, JW Earl, Renal function, haematocrit and body size affect total and unbound melphalan clearance in patients with multiple myeloma. ASCEPT. December 2009. Sydney.
6. Nath CE, Shaw PJ, Trotman J, Zeng L , Joshua D, Kerridge I, Kwan Y, Presgrave P, Tiley C, McLachlan AJ, Gurney H, Earl JW. Pharmacodynamics of high dose melphalan in myeloma. CLINICAL LYMPHOMA & MYELOMA Volume: 9 Pages: S34-S35 Supplement: Suppl. 1. Feb 2009. 12th International Myeloma Workshop. USA.
7. Nath CE, Shaw PJ, Trotman J, Zeng L, Tiley C, Joshua D, Kerridge I, Kwan Y, Presgrave P, Gurney H, McLachlan AJ and Earl JW. (2008). Optimising High Dose Melphalan in patients with multiple Myeloma: Preliminary results from a multi-centre trial. Invited oral presentation at Ehrlich II Conference in Nuremburg in October. Awarded the Paul Ehrlich Magic Bullet Award 2008.
8. Nath CE, Shaw PJ, Trotman J, Zeng L, Gurney H, McLachlan AJ, Presgrave P, Tiley C, Joshua D, Kerridge I, Kwan Y and Earl J (2008). Population pharmacokinetics of melphalan in myeloma patients. Poster presentation at AAPS, Atlanta, USA.
9. Nath CE, Shaw PJ, Trotman J, Zeng L, McLachlan AJ, Gurney H, Kwan YL, Presgrave P, Tiley C, Joshua D, Kerridge I, Kwan YL and Earl J. (2008).Population pharmacokinetics of melphalan in myeloma patients. AACB conference. Newcastle.
10. Nath CE, Shaw PJ, Trotman J, Zeng L, McLachlan AJ, Gurney H, Kwan YL, Presgrave P, Tiley C, Joshua D, Kerridge I and Earl J. (2008) Population pharmacokinetics of melphalan in myeloma patients. ASMR, Sydney.
11. Nath CE, Shaw PJ, Trotman J, Zeng L, Gurney H, McLachlan AJ, Kerridge I, Kwan Y, Presgrave P, Tiley C, Joshua D and Earl J (2008) Population pharmacokinetics of melphalan in myeloma patients undergoing an autograft. PAGANZ (Dunedin, New Zealand).
12. Nath CE, Shaw PJ, Trotman J, Zeng L, Joshua D, Kerridge I, Presgrave P, Kwan YL, Tiley C, Nivivon-Smith I, McLachlan AJ, gurney H, Booth A and Earl JW. (2007). Melphalan pharmacokinetics in myeloma. XIth International Myeloma Workshop. Haematologica - The hematology journal; 92: (6): 188 (Suppl.2).
Public notes

Contacts
Principal investigator
Name 36139 0
A/Prof Judith Trotman
Address 36139 0
Department of Haematology,
Concord Hospital,
Hospital Rd,
Concord, 2139
Country 36139 0
Australia
Phone 36139 0
61-2-97675000
Fax 36139 0
Email 36139 0
Judith.Trotman@sswahs.nsw.gov.au
Contact person for public queries
Name 10222 0
Dr Christa Nath
Address 10222 0
Department of Biochemistry
The Childrens Hospital at Westmead
Hawkesbury Rd
Locked Bag 4001
Westmead NSW 2145
Country 10222 0
Australia
Phone 10222 0
+61 2 98453287
Fax 10222 0
+61 2 98453332
Email 10222 0
christa.nath@health.nsw.gov.au
Contact person for scientific queries
Name 1150 0
Dr Christa Nath
Address 1150 0
Department of Biochemistry
The Childrens Hospital at Westmead
Hawkesbury Rd
Locked Bag 4001
Westmead NSW 2145
Country 1150 0
Australia
Phone 1150 0
+61 2 98453287
Fax 1150 0
+61 2 98453332
Email 1150 0
christa.nath@health.nsw.gov.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary