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Trial registered on ANZCTR


Trial ID
ACTRN12613000337774
Ethics application status
Approved
Date submitted
25/02/2013
Date registered
27/03/2013
Date last updated
25/05/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Pilot Study of partially Human Leucocyte Antigen (HLA)-mismatched stem cell infusions after chemotherapy for acute myeloid leukaemia in patients over the age of 60.
Scientific title
Pilot Study of partially Human Leucocyte Antigen (HLA)-mismatched stem cell infusions after chemotherapy for acute myeloid leukaemia in patients over the age of 60: an evaluation of incidence of Graft vs Host Disease and treatment related mortality.
Secondary ID [1] 281995 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukaemia > 60 yrs 288431 0
Condition category
Condition code
Blood 288780 288780 0 0
Haematological diseases
Cancer 289033 289033 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Infusion of Granulocyte Colony Stimulating Factor (G-CSF) mobilised Peripheral Blood Stem Cells (PBSCs) from a partially HLA-mismatched relative after standard induction and consolidation chemotherapy for patient with Acute Myeloid Leukaemia greater than 60 yrs of age.
PBSCs will be harvested by apheresis from the donor on day 9 (of induction chemotherapy for the patient) after administration of GCSF to the donor(10 micrograms/kg subcutaneously daily from days 5 to 8). The minimum stipulated CD34 positive cell dose will be greater than 0.5 x 10^6/kg. The total collection will be divided into 4 aliquots: 3 portions will be cryopreserved for later use and one portion will be infused into patient on the day of collection (day 9).
Induction therapy will consist of 7+3 regimen with continuous Cytarabine (150mg/m2) intravenous infusion for 7 days and Mitoxantrone (10mg/m2) intravenously daily for 3 days, followed by intravenous infusion of GCSF mobilised PBSCs on day 9. Bone marrow biopsy will be performed by day 28 +/- 7 days and if complete remission is confirmed patients will proceed with consolidation chemotherapy. If patient is not in morphologic complete remission then a further cycle of induction followed by PBSC infusion is offered.
If the patient is in remission following induction, 2 cycles of consolidation chemotherapy, comprising the 5 + 2 regimen (Mitoxantrone 10mg/m2 IV days 1 to 2 and Cytarabine 150mg/m2 continuous IV infusion days 1 to 5) will be delivered and each cycle will be followed by IV infusion of PBSCs, 36 to 48 hours after chemotherapy has been disconnected.
All of the above treatments are part of the study intervention.
Intervention code [1] 286566 0
Treatment: Other
Intervention code [2] 286804 0
Treatment: Drugs
Comparator / control treatment
Uncontrolled
Control group
Uncontrolled

Outcomes
Primary outcome [1] 288916 0
Cumulative incidence of Graft vs Host Disease assessed clinically every week during treatment phase and then at study time points (every third month for two years).
Timepoint [1] 288916 0
3, 6, 9, 12, 15, 18, 21 and 24 months
Primary outcome [2] 289106 0
Treatment Related Mortality defined as death in remission or related to the treatment, including PBSC infusion.
Timepoint [2] 289106 0
6 months
Secondary outcome [1] 301330 0
Rate of complete remission (CR) following induction chemotherapy assessed using morphological assessment of bone marrow aspirate and defined as less than 5% blasts.

Timepoint [1] 301330 0
assessed at Day 28
Secondary outcome [2] 301331 0
Time to neutrophil and Platelet recovery following chemotherapy assessed using daily full blood counts.
Timepoint [2] 301331 0
post each treatment cycle
Secondary outcome [3] 301332 0
Number of blood products infused by collecting records of packed red blood cell and platelet transfusions for each patient.
Timepoint [3] 301332 0
Day 28 of each treatment cycle
Secondary outcome [4] 301333 0
Severe infection rate following induction chemotherapy assessed clinically and with microbiological, radiological investigations during patient care.
Timepoint [4] 301333 0
Day 28
Secondary outcome [5] 301334 0
Duration of first remission, defined as time from achieving Complete Remission to Relapse (diagnosed clinically, with a full blood count and bone marrow biopsy), Death from other causes or end of followup.
Timepoint [5] 301334 0
year 1 and year 2
Secondary outcome [6] 301335 0
Overall and leukaemia free survival. Overall Survival is defined as time to death and Leukaemia free survival is defined as time from achieving CR to relapse or death.
Timepoint [6] 301335 0
year 1 and Year 2
Secondary outcome [7] 301336 0
Rate of detectable donor chimerism measured using DNA Short Tandem Repeat (STR) based testing on bone marrow samples.
Timepoint [7] 301336 0
Day 28 of each treatment cycle

Eligibility
Key inclusion criteria
Patients aged over 60 with previously untreated AML undergoing induction chemotherapy, who have an available partially HLA-mismatched donor
Minimum age
60 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patient with Acute Promyelocytic Leukaemia, Chronic Myeloid Leukaemia or unfit for induction chemotherapy or have immunodeficiency (apart from neutropenia)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients over the age of 60 years presenting with previously untreated AML. Patients with Acute Promyelocytic Leukaemia (APmL) or Chronic Myeloid Leukaemia in Blast Crisis (CML-BC) will not be eligible as there are specific targeted therapies for these conditions. The intended donor is a partially HLA-mismatched relative defined as HLA-haploidentity at HLA-A, -B, -C, and –DRB1. In most cases this would mean a biological child, although siblings and grandchildren also have a 50% chance of HLA-haploidentity. Donors must fulfill eligibility criteria as per standards published by BMT Network NSW.
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 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Current
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 635 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 6368 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 286774 0
Hospital
Name [1] 286774 0
St Vincent's Hospital, Sydney
Address [1] 286774 0
390 Victoria St
Darlinghurst NSW 2010
Country [1] 286774 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital, Sydney
Address
390 Victoria St
Darlinghurst NSW 2010
Country
Australia
Secondary sponsor category [1] 285571 0
None
Name [1] 285571 0
Address [1] 285571 0
Country [1] 285571 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288839 0
St Vincent's Hospital Human Research Ethics Committee
Ethics committee address [1] 288839 0
390 Victoria St
Darlinghurst NSW 2010
Ethics committee country [1] 288839 0
Date submitted for ethics approval [1] 288839 0
29/05/2012
Approval date [1] 288839 0
31/07/2012
Ethics approval number [1] 288839 0
HREC/12/SVH/141

Summary
Brief summary
This study aims to determine the effect of partially HLA-mismatched stem cell infusions after chemotherapy for acute myeloid leukaemia in older patients.
Who is it for? You may be eligible to join this study if you are aged between 60-85 years and have been diagnosed with acute myeloid leukaemia (AML) which has been previously untreated. You should be undergoing induction chemotherapy and have an available partially HLA-mismatched donor.
Trial details: All participants in this trial will undergo standard induction chemotherapy. Peripheral blood stem cells (PBSCs) will be collected from the available donor, then harvested and administered to the patient on day 9 of induction chemotherapy by intravenous infusion (i.e. directly into the vein). On day 28 a bone marrow biopsy will be performed, and if complete remission is confirmed then patients will proceed with two cycles of consolidation chemotherapy. If the patient is not in complete remission then a further cycle of induction chemotherapy followed by PBSC infusion is offered. Participants will be regularly assessed for up to 24 months in order to determine clinical efficacy and safety of the treatment.
Trial website
Trial related presentations / publications
nil publications,
Public notes

Contacts
Principal investigator
Name 38022 0
Dr Sam Milliken
Address 38022 0
Kinghorn Cancer Centre
St Vincent's Hospital, sydney
370 Victoria St
Darlinghurst NSW 2010
Country 38022 0
Australia
Phone 38022 0
61 2 9355 5656
Fax 38022 0
61 2 9355 5735
Email 38022 0
SVHCancer_research@stvincents.com.au
Contact person for public queries
Name 38023 0
Ms Patricia Plenge
Address 38023 0
Kinghorn Cancer Centre
St Vincent's Hospital, sydney
370 Victoria St
Darlinghurst NSW 2010
Country 38023 0
Australia
Phone 38023 0
61 2 9355 5613
Fax 38023 0
61 2 9355 5735
Email 38023 0
SVHCancer_research@stvincents.com.au
Contact person for scientific queries
Name 38024 0
Dr Sam Milliken
Address 38024 0
Kinghorn Cancer Centre
St Vincent's Hospital, sydney
370 Victoria St
Darlinghurst NSW 2010
Country 38024 0
Australia
Phone 38024 0
61 2 9355 5656
Fax 38024 0
61 2 9355 5735
Email 38024 0
SVHCancer_research@stvincents.com.au