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Trial registered on ANZCTR


Registration number
ACTRN12617000215325
Ethics application status
Approved
Date submitted
2/06/2016
Date registered
9/02/2017
Date last updated
4/06/2019
Date data sharing statement initially provided
4/06/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Orthotopic heart transplantation followed by autologous stem cell transplantation in patients with cardiac AL amyloidosis - a Phase II study
Scientific title
Orthotopic heart transplantation followed by autologous stem cell transplantation in patients with cardiac AL amyloidosis - a Phase II study
Secondary ID [1] 289354 0
none
Universal Trial Number (UTN)
Trial acronym
Cardiac Amyloid Pilot study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
AL amyloidosis with cardiac involvement 298984 0
Condition category
Condition code
Cancer 299049 299049 0 0
Myeloma
Cardiovascular 301430 301430 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients who have advanced cardiac amyloidosis who have received a heart transplant after completing Bortezomib-based or immunomodulatory (thalidomide, lenalidomide or pomalidomide) based chemotherapy, are eligible to enro in this study. The study involves eligible patients who are well enough as assessed by their treating physicians to undergo Autologous Stem Cell Transplant within 3-6 months after heart transplant.
Enrolled patients will receive melphalan 200mg/m2 for one dose intravenously the day before stem cells are infused. Prophylactic medication to prevent infection will commence as determined by treating physician. - Subcutaneous Filgrastim 5 ug/kg given daily could be considered if transplant engraftment is delayed beyond 28 days. The ASCT will follow standard guidelines by the BMT Network . Patients will be followed up clinically weekly in the first month, then every 3 months for the first year, then 6 monthly for 5 years by their treating physician after stem cell transplant using physical assessments and pathology tests - After the stem cell transplant, medical reviews will also be customised be for each patient if patient need more regular follow up.
Intervention code [1] 294933 0
Treatment: Other
Intervention code [2] 296592 0
Treatment: Drugs
Intervention code [3] 296593 0
Treatment: Surgery
Comparator / control treatment
no control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298517 0
overall surivival for AL amyloidosis patients with advanced cardiac disease who underwent tandem orthotopic heart transplantation followed by autologous stem cell transplantation.
Timepoint [1] 298517 0
every 3 months for 12 months then 6 monthly for 5 years from Day 0 HSCT
Primary outcome [2] 298656 0
progression-free survival for AL amyloidosis patients with advanced cardiac disease who underwent tandem orthotopic heart transplantation followed by autologous stem cell transplantation determined by blood tests and physician assessments
Timepoint [2] 298656 0
every 3 months for 12 months then 6 monthly for 5 years from Day 0 HSCT
Secondary outcome [1] 324437 0
Safety of autologous stem cell transplantation on HEart transplant recepient determined by blood tests and physician assessments
Timepoint [1] 324437 0
every 3 months for 12 months then 6 monthly for 5 years from Day 0 HSCT
Secondary outcome [2] 324438 0
Efficacy of autologous stem cell transplantation on Heart transplant recipient determined by testing paraprotein if applicable through blood tests
Timepoint [2] 324438 0
every 3 months for 12 months then 6 monthly for 5 years from Day 0 HSCT
Secondary outcome [3] 331471 0
Efficacy of autologous stem cell transplantation on Heart transplant recipient determined by testing troponin through blood tests
Timepoint [3] 331471 0
every 3 months for 12 months then 6 monthly for 5 years from Day 0 HSCT
Secondary outcome [4] 331472 0
Efficacy of autologous stem cell transplantation on Heart transplant recipient determined by testing ProBNPthrough blood tests
Timepoint [4] 331472 0
every 3 months for 12 months then 6 monthly for 5 years from Day 0 HSCT
Secondary outcome [5] 331473 0
Efficacy of autologous stem cell transplantation on Heart transplant recipient determined by testing serum free light chain through blood tests
Timepoint [5] 331473 0
every 3 months for 12 months then 6 monthly for 5 years from Day 0 HSCT
Secondary outcome [6] 331474 0
Efficacy of autologous stem cell transplantation on Heart transplant recipient determined by physical assessments measuring fitness level using NYHA class response
Timepoint [6] 331474 0
every 3 months for 12 months then 6 monthly for 5 years from Day 0 HSCT

Eligibility
Key inclusion criteria
1. Cardiac AL Amyloidosis, Stage III (a) or (b) prior to heart transplantation
2. received orthotopic heart transplantation
3. adequate cardiac function: Ejection fraction > 50%, no restrictive cardiomyopathy in echocardiogram or cardiac MRI
4. absence of cardiac rejection
5. no evidence of amyloid infiltration to the cardiac allograft
6. Measurable light chains prior to induction chemotherapy (FLC > 1.5xULN with abnormal kappa:lambda ratio)
7. Measureable NT-ProBNP and Troponin-T prior to induction chemotherapy
8. ECOG status of less than 2 or Karnofsky score less than 60 (see appendix B)
9. Able to provide informed consent
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Amyloidosis other than AL Amyloidosis. This includes AA amyloidosis, senile amyloidosis, heritable amyloidosis (including but not limited to transerythin (ATTR) cardiac amyloidosis). Patients will require a negative genetic screen for heritable amyloidosis at Westmead Hospital Amyloid unit.
2. Diagnosis of multiple myeloma with more than 20% bone marrow plasma cells with end-organ involvement
3. Diagnosis of other haematological or solid organ malignancies
4. Other Amyloidosis-related end-organ diseases including renal disease (creatinine greater than 2x ULN), hepatic failure (AST, ALT greater than 3x ULN, Bilirubin > 2x ULN)
5. Significant cytopenias: Haemoglobin level <80g/L, neutrophil count <1x109/L, platelet count <75x109/L
6. Hepatitis B, C or HIV seropositivity
7. Pregnancy or breastfeeding
8. Patient with other serious medical or psychiatric illness likely to interfere with participation in this clinical study
9. Greater than grade 1 peripheral neuropathy
10. Smoking or intravenous drug use within 6 months of potential cardiac transplant

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)
Not applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Descriptive statistics will be used to measure primary and secondary outcomes in this pilot study- as this study will only recruit 20 patients - analysis will be done only within this group.

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
Recruitment hospital [1] 5886 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 13333 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 293736 0
Hospital
Name [1] 293736 0
St Vincent's Hospital,Sydney
Address [1] 293736 0
390 Victoria St
Darlinghurst NSW 2010
Country [1] 293736 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] 292565 0
None
Name [1] 292565 0
Address [1] 292565 0
Country [1] 292565 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295170 0
St Vincents Hospital, Sydney Human Research Ethics Committee (HREC)
Ethics committee address [1] 295170 0
390 Victoria St Darlinghurst NSW 2010
Ethics committee country [1] 295170 0
Australia
Date submitted for ethics approval [1] 295170 0
02/05/2016
Approval date [1] 295170 0
31/05/2016
Ethics approval number [1] 295170 0
HREC/16/SVH/123

Summary
Brief summary
This study aims to investigate the safety and efficacy of autologous stem cell transplantation in AL amyloid patients with advanced cardiac disease.
after a orthotopic heart transplantation.
Who is it for?
You may be eligible to join this study if you are aged between 18-65 years and have been diagnosed with cardiac AL amyloidosis.

Study details
All participants in this study are required to have previously received chemotherapy and a orthotopic heart transplantation before being enrolled in the study to received an autologous stem cell transplantation. Patients will undergo autologous stem cell transplantation (ASCT) within 3-6 months after OHT.

patient will have an Autologous stem cell transplant using Melphalan 200mg/m2 on day -1 with stem cell collected given on day 0 previously from the patient before the study.

All participants will be followed up every 3 to 6 months for a period of 5 years, in order to assess survival, and safety and efficacy of treatment.

This pilot study will determine if treating patient with a stem cell transplant with cardiac amyloid after receiving a heart transplant will increase disease free survival
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 66378 0
A/Prof John Moore
Address 66378 0
St Vincent's Hospital, Sydney
390 Victoria St
Darlinghurst NSW 2010
Country 66378 0
Australia
Phone 66378 0
+61 2 9355 5656
Fax 66378 0
+61 2 9355 5735
Email 66378 0
SVHS.CancerResearch@svh.org.au
Contact person for public queries
Name 66379 0
Dr Kris Ma
Address 66379 0
St Vincent's Hospital, Sydney
390 Victoria St
Darlinghurst NSW 2010
Country 66379 0
Australia
Phone 66379 0
+61 2 9355 5656
Fax 66379 0
+61 2 9355 5735
Email 66379 0
SVHS.CancerResearch@svh.org.au
Contact person for scientific queries
Name 66380 0
Dr Kris Ma
Address 66380 0
St Vincent's Hospital, Sydney
390 Victoria St
Darlinghurst NSW 2010
Country 66380 0
Australia
Phone 66380 0
+61 2 9355 5656
Fax 66380 0
+61 2 9355 5735
Email 66380 0
SVHS.CancerResearch@svh.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No ethics approved to share
What supporting documents are/will be available?
No other documents available
Summary results
No Results