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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12618000505202
Ethics application status
Approved
Date submitted
15/03/2018
Date registered
6/04/2018
Date last updated
13/06/2019
Date data sharing statement initially provided
13/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Study of using Cyclophosphamide After Sibling-donor allogeneic stem-cell Transplantation (CAST) in patients with acute leukaemia and myelodysplasia
Scientific title
Study of using Cyclophosphamide After Sibling-donor allogeneic stem-cell Transplantation (CAST) in patients with acute leukaemia and myelodysplasia: a randomised study comparing cyclosporin and methotrexate to cyclosporin and post-transplantation cyclophosphamide for graft-versus-host disease prophylaxis.
Secondary ID [1] 294348 0
ALLG BM12
Universal Trial Number (UTN)
Trial acronym
CAST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Leukaemias 307071 0
Myelodysplasia 307129 0
Condition category
Condition code
Blood 306178 306178 0 0
Haematological diseases
Cancer 306240 306240 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The GVHD prophylaxis consists of post-transplant iv cyclophosphamide 50 mg/kg on Day +3, +4 and oral cyclosporin commencing on Day +5, Cyclosporin lasts 90 days
Cyclosporin dosing is as per institution’s standard practice. The protocol recommends maintaining trough cyclosporin level at > 140 µg/l in the absence of toxicity
Intervention code [1] 300650 0
Treatment: Drugs
Comparator / control treatment
The GVHD prophylaxis consists of oral cyclosporin starting from day -1 and iv methotrexate 15 mg/m2 day +1 and 10 mg/m2 on days +3, +6 and +11.
Cyclosporin lasts 90 days
Cyclosporin dosing is as per institution’s standard practice. The protocol recommends maintaining trough cyclosporin level at > 140 µg/l in the absence of toxicity
Control group
Active

Outcomes
Primary outcome [1] 305188 0
Graft versus host disease and relapse free survival (GRFS) - composite endpoint

GVHD-free/relapse-free survival (GRFS) is measured from the date of allogeneic HSCT to the earliest occurrence of any of the following events: grade 3-4 acute GVHD, NIH moderate or severe chronic GVHD, disease relapse or death from any cause.
Timepoint [1] 305188 0
24 months post transplant
Secondary outcome [1] 344457 0
Non relapse mortality

Death without prior relapse of disease. All survival times measured from the date of HSCT.
Timepoint [1] 344457 0
12 and 24 months post transplant
Secondary outcome [2] 344876 0
Health related QoL
1. The Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) questionnaire includes 27 items assessing 4 aspects of well-being (physical, functional, emotional, social/family), plus 23 symptoms and issues specific to bone marrow transplant. The FACT-BMT is valid responsive to change over and well-suited to this trial due to the clinical relevance of scale items. It will also enable calculation of the FACT-8D utility scores

2. The FACT-Fatigue includes 13 items assessing symptoms and consequences of fatigue. It has been validated in a cancer population.

3. The Physical functioning sub-scale of the EORTC QLQ-C30, which contains 5 items, will be used to supplement the physical wellbeing scale of the FACT-BMT, to obtain a clearer estimate of the impact of the disease and treatment on mobility and self-care issues. It adds 13 items to the PRO assessment battery.

4. The EQ-5D-5L is a preference-based measure of QoL that will be used to estimate health utilities scores and combined with survival endpoints to calculate quality-adjusted life years for incorporation in health economic analyses.

5. The COST-FACIT (version 1) includes 11 items assessing patients’ perceptions of their financial situation and the financial burden of their disease and treatment.

HRQoL is a single secondary outcome, measured using multiple instruments
Timepoint [2] 344876 0
12 and 24 months post-transplant

Eligibility
Key inclusion criteria
• 18-70 years of age
• Adult patients with AML/ALL in remission or MDS with <20% myeloblasts
• Availability of 6/6-matched sibling donor
• Adequate cardiac (LVEF greater than or equal to 40%), pulmonary (DLCO/VA >50%) and renal function (Creatinine Clearance greater than or equal to 60 ml/min).
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Donor other than a sibling
• Graft source other than G-CSF mobilised PBSC
• Use of in-vitro or in-vivo T-cell depletion
• Life expectancy from co-morbid medical conditioning less than 12 months
• Uncontrolled infection

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 13986 0
The Alfred - Prahran
Recruitment hospital [2] 13987 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 13988 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 13989 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [5] 13990 0
Westmead Private Hospital - Westmead
Recruitment postcode(s) [1] 26764 0
3050 - Royal Melbourne Hospital
Recruitment postcode(s) [2] 26765 0
3004 - Prahran
Recruitment postcode(s) [3] 26766 0
5000 - Adelaide
Recruitment postcode(s) [4] 26767 0
6150 - Murdoch
Recruitment postcode(s) [5] 26768 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 298991 0
Government body
Name [1] 298991 0
NHMRC
Address [1] 298991 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 298991 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Australasian Leukaemia and Lymphoma Group
Address
Ground Floor, 35 Elizabeth St
Richmond, VIC 3121
Country
Australia
Secondary sponsor category [1] 298217 0
None
Name [1] 298217 0
Address [1] 298217 0
Country [1] 298217 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299920 0
Alfred Health Ethics Committee
Ethics committee address [1] 299920 0
55 Commercial Road
Melbourne, VIC 3004
Ethics committee country [1] 299920 0
Australia
Date submitted for ethics approval [1] 299920 0
23/04/2018
Approval date [1] 299920 0
22/10/2018
Ethics approval number [1] 299920 0

Summary
Brief summary
This study aims to demonstrate a drug called cyclophosphamide is better than the current standard of care at preventing graft versus host disease in patients who have just had a bone marrow transplant.

Who is it for?
You may be eligible for this study if you are aged 18-70 and have AML or ALL which is in remission, or MDS with <20% myeloblasts; and have a 6/6 matched sibling bone marrow donor.

Study details
Participants in this study will be randomly assigned (by chance) to one of two treatments. One group will take the study medication cyclophosphamide for 5 days, followed by 90 days of cyclosporin. The other group will take an existing medication regimen of cyclosporine and methotrexate, which is the current standard of care for preventing GVHD. Participants will be followed-up for 2 years post-transplant. The study will look at the number of patients in each treatment arm who develop GVHD, and how each treatment affects the patient quality of life.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 81990 0
Dr Sushrut Patil
Address 81990 0
Level 1, Alfred Centre - Alfred Hospital
55 Commercial Road
Melbourne VIC 3004
Country 81990 0
Australia
Phone 81990 0
+61 3 9903 0225
Fax 81990 0
Email 81990 0
s.patil@alfred.org.au
Contact person for public queries
Name 81991 0
A/Prof David Curtis
Address 81991 0
Level 1, Alfred Centre - Alfred Hospital
55 Commercial Road
Melbourne VIC 3004
Country 81991 0
Australia
Phone 81991 0
+61 3 9903 0225
Fax 81991 0
Email 81991 0
david.curtis@monash.edu
Contact person for scientific queries
Name 81992 0
A/Prof David Curtis
Address 81992 0
Level 1, Alfred Centre - Alfred Hospital
55 Commercial Road
Melbourne VIC 3004
Country 81992 0
Australia
Phone 81992 0
+61 3 9903 0225
Fax 81992 0
Email 81992 0
david.curtis@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No individual participant data will be publicly available as it is the aggregate data that is under investigation.
What supporting documents are/will be available?
Study protocol
Summary results
No Results