Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12607000347460
Ethics application status
Not required
Date submitted
27/06/2007
Date registered
27/06/2007
Date last updated
18/06/2021
Date data sharing statement initially provided
18/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase III Study Comparing Low Dose Cyclosporine, Methotrexate And Prednisone Versus Standard Dose Cyclosporine and Methotrexate As Graft Versus Host Disease Prophylaxis In Myeloblative Allogeneic Stem Cell Transplantation (ALLG BM10 trial).

(Incorporating an Open-Label Sub-study Investigating The Use Of Valganciclovir In The Prevention Of Cytomegalovirus Infection In Hematopoietic Stem Cell Transplant Recipients (ML20712))
Scientific title
A Phase III Study Comparing Low Dose Cyclosporine, Methotrexate And Prednisone Versus Standard Dose Cyclosporine and Methotrexate As Graft Versus Host Disease Prophylaxis In Myeloblative Allogeneic Stem Cell Transplantation (ALLG BM10 trial) in patients with haematological malignancies.

(Incorporating an Open-Label Sub-study Investigating The Use Of Valganciclovir In The Prevention Of Cytomegalovirus Infection In Hematopoietic Stem Cell Transplant Recipients in patients with haematological malignancies
Secondary ID [1] 377 0
Australasian Leukaemia and Lymphoma Group (ALLG): ALLG BM10
Universal Trial Number (UTN)
Trial acronym
nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Graft Versus Host Disease 1898 0
Prophylaxis In Myeloblative 1899 0
Allogeneic Stem Cell 1900 0
Transplantation 1901 0
Prevention Of Cytomegalovirus 1902 0
Infection In Hematopoietic Stem 1903 0
Cell Transplant Recipients 1904 0
Condition category
Condition code
Surgery 1993 1993 0 0
Other surgery
Inflammatory and Immune System 1994 1994 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Randomised trial of graft versus host disease prophylaxis: Study Intervention – Reduction of cyclosporine (to 1mg/kg intravenously D-1 to D+15 post transplant) followed by oral cyclosporine targeted at 100-200 ug/l until D110 and addition of prednisone (orally from D16 to D110 commencing at 0.5mg/kg/day).
Prevention Of Cytomegalovirus (CMV) Infection substudy. A phase II study assessing the use of valganciclovir in stem cell transplant recipients to prevent and treat CMV infection. Valganciclovir 900mg will be continued until D100. CMV viraemia and disease will be assessed until 6 months post transplant with the primary endpoint being the incidence of CMV infection at 6 months.
Intervention code [1] 1856 0
Treatment: Drugs
Comparator / control treatment
Control - Cyclosporine 3mg/kg intravenously D-1 to D+15 followed by oral cyclosporine targeted at 200-400 ug/l without prednisone until D110.
Control group
Active

Outcomes
Primary outcome [1] 2816 0
Disease-free survival and overall survival will be the primary endpoints of the randomized study.
Timepoint [1] 2816 0
At 2 years.
Primary outcome [2] 2817 0
The incidence of cytomegalovirus infection (defined as viraemia as measured by quantitative polymerase chain reaction and/or organ specific disease) will be the primary endpoint for the sub-study.
Timepoint [2] 2817 0
At 6 months.
Secondary outcome [1] 4748 0
Transplant related mortality
Timepoint [1] 4748 0
At day 100
Secondary outcome [2] 4749 0
Incidence of Acute Graft versus Host Disease
Timepoint [2] 4749 0
At day 100
Secondary outcome [3] 4750 0
Incidence of Chronic Graft Versus Host Disease
Timepoint [3] 4750 0
At 1 and 2 year intervals

Eligibility
Key inclusion criteria
2. Presence of a haematological malignancy, for which myeloblative allogeneic haematopoietic stem cell transplant is considered appropriate therapy.3. Disease status: acute myeloblastic leukaemia, acute lymphoblastic leukaemia (ALLG), Philadelphia positive ALL in first or later complete remission, chronic myeloid leukaemia (CML), multiple myeloma, non-hodgkin’s lymphoma, Hodgkin’s lymphoma in first or later complete remission, myelodisplastic syndrome. Myelofibrosis and other haematological malignancies are also included. 4. Ability to give informed consent.5. Preserved functional status (Eastern Cooperative Oncology Group performance status <2).6. Left ventricular ejection fraction > 45%. 7. Diffusing capacity of the lung for carbon monoxide > 50% of normal on pulmonary function testing.8. Serum Creatinine <150 umol/L9. Serum Bilirubin < 40mmol/l, AST < 3 x upper limit of normal.10. Availability of a willing, 7/8 or 8/8 human leukocyte antigens (HLA) -matched sibling or unrelated stem cell donor matched at HLA A, B, C and DRB1 (One antigen mismatch at Class I is permissible if no other suitable donor is available).11. Ability to harvest > 2.0 x 106/kg CD34 peripheral blood stem cells.
Minimum age
16 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Human immunodeficiency virus sero-positive2. Life expectancy less than 3 months.3. Psychiatric condition preventing the patient from providing informed consent.4. Pregnant or lactating women.5. History of active malignant disease within the previous 5 years excluding basal cell carcinoma or sqamous cell carcinoma of the skin.6. Previous allogeneic stem cell transplant7. More than 2 previous autografts

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)
Central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The method is stratified permuted block design with stratification by age, donor type, cytomegalovirus status and disease risk. The 16 strata in the design will be will be allocated by computerised generation via blocks
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
The major reason for withdrawal is the current difficulties with the TGA and the use of off-licence drugs.
Date of first participant enrolment
Anticipated
15/07/2007
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 2134 0
Government body
Name [1] 2134 0
Commonwealth Department of Health and Ageing
Country [1] 2134 0
Australia
Funding source category [2] 2135 0
Hospital
Name [2] 2135 0
St Vincent’s Hospital
Country [2] 2135 0
Australia
Funding source category [3] 2136 0
Commercial sector/Industry
Name [3] 2136 0
Roche Australia
Country [3] 2136 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group
Address
35 elisabeth Street Vic 3121
Country
Australia
Secondary sponsor category [1] 1940 0
None
Name [1] 1940 0
nil
Address [1] 1940 0
Country [1] 1940 0

Ethics approval
Ethics application status
Not required

Summary
Brief summary
Stem cell transplantation has the potential to cure many patients with blood cancers. These cures occur when immune cells from the donor attack blood cancer cells left in the patient. This is called the graft versus leukaemia (GVL) effect. These immune cells also cause a reaction against the patient called graft versus host disease (GVHD), which can be serious and life threatening. Thus, one of the major goals of transplantation today is is to reduce GVHD and increase GVL. The drugs cyclosporine and prednisone are used to reduce graft versus host disease in over 90% of transplants performed in Australia and New Zealand. The aim of this study is to reduce the dose of cyclosporine which may increase the GVL effect and add a higher dose of prednisone which may inhibit GVHD – this is the intervention. This new combination of these two drugs will be compared to the standard dose of cyclosporine which has been used for many years – this will be the control group. Patients will be followed for 2 years to assess whether this change in drugs will result in more patients being cured of their blood cancers.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27670 0
Dr Dr. John Moore
Address 27670 0
St Vincents Hospital, NSW
Country 27670 0
Australia
Phone 27670 0
+61 0283822677
Fax 27670 0
02 83832645
Email 27670 0
jmoore@stvincents.com.au
Contact person for public queries
Name 11045 0
Dr Dr. John Moore
Address 11045 0
Haematology Department St. Vincents Hospital Victoria Rd Darlinghurst NSW2010
Country 11045 0
Australia
Phone 11045 0
61 2 83822677
Fax 11045 0
61 2 83822645
Email 11045 0
jmoore@stvincents.com.au
Contact person for scientific queries
Name 1973 0
Dr Dr. John Moore
Address 1973 0
Haematology Department, St. Vincents Hospital, Victoria Rd, Darlinghurst, NSW, 2010
Country 1973 0
Australia
Phone 1973 0
61 2 83822677
Fax 1973 0
61 2 83822645
Email 1973 0
jmoore@stvincents.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.