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Trial registered on ANZCTR


Registration number
ACTRN12613001154796
Ethics application status
Approved
Date submitted
9/10/2013
Date registered
16/10/2013
Date last updated
16/10/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase 2 trial of a preventative treatment (cyclophosphamide) for graft-versus-host disease after matched (HLA-identical) allogeneic donor transplant using less intensive chemotherapy
Scientific title
A phase 2 trial of cyclophosphamide as prophylaxis for graft-versus-host disease after HLA-identical allogeneic donor transplantation using reduced intensity conditioning therapy
Secondary ID [1] 283363 0
None
Universal Trial Number (UTN)
U1111-1148-8349
Trial acronym
PT CYCLO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Graft versus Host Disease 290261 0
Haematological malignancy 290308 0
Condition category
Condition code
Inflammatory and Immune System 290651 290651 0 0
Other inflammatory or immune system disorders
Blood 290684 290684 0 0
Haematological diseases
Cancer 290703 290703 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Cyclophosphamide 50 mg/kg on days +3 and +4 post transplant (2 doses)by intravenous infusion over 1 hour
Intervention code [1] 288088 0
Treatment: Drugs
Intervention code [2] 288116 0
Prevention
Comparator / control treatment
ATG is given as a single dose of 30 mg/kg IV on day -1.

MMF is given from day +1 at a dose of 15/mg/kg po every 8 hours, with a total maximum daily dose of 3g, up to day +35.

Cyclosporin is given from day -1 to day 180 in 2 divide
d doses to maintain a therpeutic blood level of 100-250 ng/ml. Initial IV dosing is started at 1.5 mg/kg 12 hourly.



Historical data from departmental database over five years (2008-2012)
Control group
Historical

Outcomes
Primary outcome [1] 290667 0
The primary objective will be to determine the rates of acute GVHD grade III-IV assessed on clinical and laboratory results, according to the consensus criteria published in Przepiorka BMT 1995.
Timepoint [1] 290667 0
100 days post-transplant
Secondary outcome [1] 304996 0
Transplant-related mortality
Timepoint [1] 304996 0
100 days, 1 and 2 years
Secondary outcome [2] 304997 0
Rates of acute GVHD of all grades assessed on clinical and laboratory results, according to the consensus criteria published in Przepiorka BMT 1995.
Timepoint [2] 304997 0
Up to 100 days post-transplant
Secondary outcome [3] 304998 0
The rate of chronic GVHD Chronic GVHD graded on clinical and laboratory criteria, according to NIH consensus criteria (Filipovich AH, Weisdorf D, Pavletics S, et al. National Institute of Health consensus development project on
criteria for clinical trials in chronic Graft-versus-host disease: I. Diagnosis and Staging Working group report. Biol Blood Marrow Transplant. 2005; 11:945-956.)
Timepoint [3] 304998 0
2 years
Secondary outcome [4] 304999 0
Relapse rate will be assessed on clinical, laboratory, and radiological criteria appropriate for the disease in question.
Timepoint [4] 304999 0
2 years
Secondary outcome [5] 305000 0
Details of treatment for acute GVHD, in particular use of calcineurin inhibitors and salvage treatment for steroid-refractory acute GVHD
Timepoint [5] 305000 0
Up to 100 days post-transplant
Secondary outcome [6] 305001 0
Disease-free survival will be calculated from the time of transplant until date of last follow-up, or the earlier of the dates of disease relapse or death
Timepoint [6] 305001 0
2 years

Eligibility
Key inclusion criteria
1. Age 15-70 years
2. High risk hematological malignancy suitable for treatment with an allogeneic transplant (acute leukaemia in first remission with poor risk cytogenetics or unfavourable gene mutation profile, or in second or subsequent remission, chronic myeloid leukaemia in first chronic phase not responding to tyrosine kinase inhibitor therapy, poor risk myelodysplastic syndrome, Hodgkin or non-Hodgkin lymphoma failing conventional therapy).
3. Suitable HLA-matched related donor (6/6 match for A, B, DRB1) or unrelated volunteer donor (8 locus match for A, B, C, and DRB1 at allelic level) identified and available.
Minimum age
15 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Serious organ dysfunction or uncontrolled infection
2. HIV positive
3. Uncontrolled hepatitis B or C.

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



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
This is an exploratory Phase II trial and, as it is likely that enrolment of the majority of patients receiving HLA-matched sibling transplants will be enrolled into cell-therapy based trials at Westmead, this study therefore will focus on matched unrelated donor transplants. In the five years 2008-2012, Westmead carried out 61 transplants using RIC therapy and unrelated donors. There were 8 cases of acute GVHD grades III-IV (13%). Based on a similar annual accrual of 12 patients, and an accrual period of 2 years, we expect to be able to enrol 24 patients onto this study. Interim monitoring for rates of acute GVHD grades III-IV will be based on the historical figure of 13% observed using ATG, cyclosporin and mycophenolate as GVHD prophylaxis. GVHD data will be reviewed 100 days after the 12th patient is accrued and if 4 or more cases are observed the trial will be closed. If less than 4 cases are observed the trial will conitue to accrue. Similarly, if after 18 patients are enrolled there are less than 5 cases of GVHD grades III-IV, accrual will continue to a total of 24, while if 5 or more are observed the regimen will be re-assessed or study be closed. These boundaries are based on the charts of Metha and Cain (1984),and are consistent with a 95% confidence of an underlying rate of 13% or lower,

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/03/2014
Actual
Date of last participant enrolment
Anticipated
1/03/2016
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 1579 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 7414 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 288091 0
Hospital
Name [1] 288091 0
Westmead Hospital
Country [1] 288091 0
Australia
Primary sponsor type
Hospital
Name
Westmead Hospital
Address
Westmead Hospital
Cnr Hawkesbury & Darcy Roads
Westmead NSW 2145
Country
Australia
Secondary sponsor category [1] 286813 0
None
Name [1] 286813 0
Address [1] 286813 0
Country [1] 286813 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290016 0
Western Sydney Local Health District
Ethics committee address [1] 290016 0
Ethics committee country [1] 290016 0
Australia
Date submitted for ethics approval [1] 290016 0
16/10/2013
Approval date [1] 290016 0
Ethics approval number [1] 290016 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 43490 0
Prof Ken Bradstock
Address 43490 0
Westmead Hospital
Cnr Hawkesbury & Darcy Roads
Westmead NSW 2145
Country 43490 0
Australia
Phone 43490 0
61298457073
Fax 43490 0
61296892331
Email 43490 0
kbradstock@gmail.com
Contact person for public queries
Name 43491 0
Angela Bayley
Address 43491 0
Westmead Hospital
Cnr Hawkesbury & Darcy Roads
Westmead NSW 2145
Country 43491 0
Australia
Phone 43491 0
61298457219
Fax 43491 0
61296893700
Email 43491 0
angela.bayley@sydney.edu.au
Contact person for scientific queries
Name 43492 0
Ken Bradstock
Address 43492 0
Westmead Hospital
Cnr Hawkesbury & Darcy Roads
Westmead NSW 2145
Country 43492 0
Australia
Phone 43492 0
61298457073
Fax 43492 0
61296893700
Email 43492 0
kbradstock@gmail.com

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseSingle-agent high-dose cyclophosphamide for graft-versus-host disease prophylaxis in human leukocyte antigen-matched reduced-intensity peripheral blood stem cell transplantation results in an unacceptably high rate of severe acute graft-versus-host disease.2015https://dx.doi.org/10.1016/j.bbmt.2015.01.020
N.B. These documents automatically identified may not have been verified by the study sponsor.