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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]

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

Condition category

Condition code

Cancer

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]

Treatment: Drugs

Comparator / control treatment

No control group.

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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]

Measured after a single dose.

Primary outcome [2]

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]

Collected prior to the melphalan dose and autologous transplant, on study enrolment.

Primary outcome [3]

3. Transplant related toxicity including mucositis, gastrointestinal toxicity, haematological toxicity, and other toxicities

Timepoint [3]

Followed for up to 4 weeks post the melphalan dose and autologous transplant.

Primary outcome [4]

4. Disease response and survival

Timepoint [4]

Followed for up to 2 years post transplant.

Primary outcome [5]

5. Statistical methods will be used to identify a target AUC range that is associated with a good outcome with acceptable toxicity.

Timepoint [5]

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]

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]

When data from 60 patients has been collected. This analysis is currently being performed.

Secondary outcome [1]

Nil

Timepoint [1]

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

Sex

Both males and females

Can healthy volunteers participate?

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

1/01/2006

Actual

21/04/2004

Date of last participant enrolment

Anticipated

Actual

29/06/2010

Date of last data collection

Anticipated

Actual

1/08/2013

Sample size

Target

140

Accrual to date

Final

120

Recruitment in Australia

Recruitment state(s)

Recruitment postcode(s) [1]

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

NHMRC project grant 396702

Address [1]

MDP 70,
GPO Box 9848
Canberra, ACT, 2601

Country [1]

Australia

Primary sponsor type

Hospital

Name

The Childrens Hospital at Westmead

Address

Hawkesbury Rd. Westmead, NSW, 2145

Country

Australia

Secondary sponsor category [1]

Hospital

Name [1]

Concord Hospital

Address [1]

Hospital Rd.
Concord, NSW, 2139

Country [1]

Australia

Secondary sponsor category [2]

Other Collaborative groups

Name [2]

Cancer Trials NSW

Address [2]

153 Dowling St.
Woolloomooloo,
NSW, 2011

Country [2]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Concord Hospital

Ethics committee address [1]

Hospital Rd. 
Concord, NSW, 2139

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

16/03/2004

Ethics approval number [1]

CH62/6/2004-016

Ethics committee name [2]

Wollongong Hospital

Ethics committee address [2]

Loftus St.
Wollongong, 
NSW, 2500

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

Approval date [2]

05/04/2005

Ethics approval number [2]

HE05/075

Ethics committee name [3]

Royal Prince Alfred Hospital

Ethics committee address [3]

Missenden Rd. 
Camperdown, NSW, 2050

Ethics committee country [3]

Australia

Date submitted for ethics approval [3]

Approval date [3]

02/06/2004

Ethics approval number [3]

X04-0105

Ethics committee name [4]

St George Hospital

Ethics committee address [4]

South St. 
Kogarah, 
NSW, 2217

Ethics committee country [4]

Australia

Date submitted for ethics approval [4]

Approval date [4]

08/02/2005

Ethics approval number [4]

05/06

Ethics committee name [5]

Westmead Hospital

Ethics committee address [5]

Hawkesbury Rd.
Westmead, NSW, 2145

Ethics committee country [5]

Australia

Date submitted for ethics approval [5]

Approval date [5]

09/06/2004

Ethics approval number [5]

2004/4/4.13(1831)

Ethics committee name [6]

Gosford Hospital

Ethics committee address [6]

Cnr Holden Street and Racecourse Road, GOSFORD NSW 2250

Ethics committee country [6]

Australia

Date submitted for ethics approval [6]

Approval date [6]

19/01/2006

Ethics approval number [6]

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

A/Prof Judith Trotman

Address

Department of Haematology,
Concord Hospital,
Hospital Rd,
Concord, 2139

Country

Australia

Phone

61-2-97675000

Fax

[email protected]

Contact person for public queries

Name

Christa Nath

Address

Department of Biochemistry
The Childrens Hospital at Westmead
Hawkesbury Rd
Locked Bag 4001
Westmead NSW 2145

Country

Australia

Phone

+61 2 98453287

Fax

+61 2 98453332

[email protected]

Contact person for scientific queries

Name

Christa Nath

Address

Department of Biochemistry
The Childrens Hospital at Westmead
Hawkesbury Rd
Locked Bag 4001
Westmead NSW 2145

Country

Australia

Phone

+61 2 98453287

Fax

+61 2 98453332

[email protected]

No information has been provided regarding IPD availability

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No Supporting Document Provided

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