ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

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

ACTRN12620001339943

Ethics application status

Approved

Date submitted

26/10/2020

Date registered

11/12/2020

Date last updated

23/11/2021

Date data sharing statement initially provided

11/12/2020

Type of registration

Prospectively registered

Titles & IDs

Public title

REscuing bone marrow function in patients with aplaStic anaEmia and bone marrow faiLure post allogEneiC Transplantation (RESELECT)
Phase I/II single arm with historical control study assessing the efficacy and safety of Atorvastatin and N-Acetyl Cysteine in the treatment of Poor Graft Function post allogeneic transplantation and relapsed/refractory aplastic anaemia

Scientific title

Secondary ID [1]

Nil

Universal Trial Number (UTN)

U1111-1260-1760

Trial acronym

RESELECT

Linked study record

Health condition

Health condition(s) or problem(s) studied:

One of the health conditions being studied in this trial will be Poor Graft Function

One of the health conditions being studied in this trial will be Aplastic Anaemia

Condition category

Condition code

Blood

Haematological diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

This is a Phase I/II single arm, with historical cohort study assessing the efficacy and safety of:
Atorvastatin tablet
10mg daily orally
N-Acetyl Cysteine capsule
600mg twice a day orally
Both taken for 12 weeks in total
In the treatment of Poor Graft Function post allogeneic transplant and relapsed refractory Aplastic Anaemia. Adherence will be assessed by reviewing bottle returns

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

A historic control group will be used. This historical group is made up of patients who received allogeneic stem cell transplants performed at the Royal Melbourne Hospital between the years 2000-2016 and fulfilled the inclusion criteria for this study. This control group was only treated with best supportive care made up of transfusion support in the setting of thrombocytopenia and anaemia and filgrastim in the setting of neutropenia

Control group

Historical

Outcomes

Primary outcome [1]

Complete Response (CR) defined as neutrophils greater than or equal to 1.5x10^9 and platelets greater than or equal to 100x10^9 without use of transfusions or cytokine support at 12 weeks
This outcome will be measured by a full blood examination performed on a blood sample at 12 weeks.

Timepoint [1]

The primary timepoint will be measured at 12 weeks post trial enrollment

Primary outcome [2]

Incidence of non haematological Adverse Events (AEs) of Grade 2 severity as measured by version 5 of the National Institute of Health common terminology criteria of adverse events (NIH-CTCAE) directly attributed to the trial medication as measured at 12 weeks.

Timepoint [2]

12 weeks

Secondary outcome [1]

Relapse free survival (RFS) in patients with PGF. This will be assessed by data collected from the participant's medical record as well as trial assessments.

Timepoint [1]

The secondary outcome of RFS will be measured 12 months post trial enrollment

Secondary outcome [2]

Overall Survival from time of enrolment. This will be assessed by data collected from the participant's medical record as well as trial assessments

Timepoint [2]

This secondary outcome of OS will be measured 12 months post trial enrollment

Secondary outcome [3]

Cumulative incidence of acute and chronic graft versus host disease (GVHD). This will be assessed by data collected from the participant's medical record as well as trial assessments

Timepoint [3]

The cumulative incidence of acute and chronic GVHD will be assessed at mandated timepoints week 1,4,8,12, 6 months, 9, months and 12 months post trial enrollment

Secondary outcome [4]

Cumulative incidence of recovery from PGF/AA. This will be assessed by data collected from full blood examination performed on blood samples taken at trial assessment points

Timepoint [4]

The cumulative incidence of recovery from PGF/AA will be assessed at mandated timepoints: week 1,4,8,12, 6 months, 9, months and 12 months post trial enrollment

Secondary outcome [5]

Cumulative incidence of non-relapse mortality (NRM). This will be assessed by data collected from the participant's medical record as well as trial assessments.

Timepoint [5]

12 months post trial enrollment.

Eligibility

Key inclusion criteria

1. Poor Graft function OR Relapsed/refractory AA defined as the following
Poor Graft Function:
Two Lineage cytopenias defined as
-Thrombocytopenia
i)Less than or equal to 30x10^9 /L from D40-D60 OR
ii)Less than or equal to 50 x10 ^9/L from D60 onwards
-Neutropenia requiring filgrastim support at any time post D40
-Hb less than or equal to 80g/L
Relapsed /Refractory AA:
Relapse after stem cell transplant OR relapsed post/refractory to 1st line immunosuppression without an unrelated donor identified.
2. Age greater than or equal to 17 years
3. ECOG performance status 0-1
4. Life expectancy > 6 months
5. Patient’s written informed consent

Minimum age

17 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Active Grade 3-4 acute GVHD
2. Relapsed or progressive disease on screening bone marrow biopsy or most recent PET imaging.
3. Active second malignancy currently requiring treatment
4. Human Immuno-deficiency Virus (HIV) infection.
5. Any coexisting medical or psychological condition that would preclude participation in the required study procedures.
6. Female patients who are both lactating and breast-feeding or have a positive serum pregnancy test during the screening period or a positive pregnancy test on Day 1 before first dose of study drug
7. Prior history of statin induced myopathy
8. Prior history of severe asthma

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

Other

Other design features

A historical comparator group will be used

Phase

Phase 1 / Phase 2

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Toxicities will be described according to type and grade as frequencies. A list of all serious adverse events will be reported.
Efficacy outcomes will be reported using descriptive statistics of the efficacy endpoints. The primary outcome will be analysed using logistic regression. Overall survival (OS) will also be assessed, defined as the time from the data of the first dose of study medication to the date of death from any cause. OS will be estimated with the Kaplan-Meier method.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

26/02/2021

Actual

28/09/2021

Date of last participant enrolment

Anticipated

31/12/2022

Actual

Date of last data collection

Anticipated

26/02/2024

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,WA,VIC

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Maddie Riewoldt's Vision

Address [1]

11 Hume St, Huntingdale VIC 3166

Country [1]

Australia

Primary sponsor type

Hospital

Name

The Royal Melbourne Hospital

Address

300 Grattan Street
Parkville
VIC 3050

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

The Royal Melbourne Hospital HREC

Ethics committee address [1]

300
Grattan Street
Parkville 
VIC 3050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

27/10/2020

Approval date [1]

21/01/2021

Ethics approval number [1]

Summary

Brief summary

Allogeneic Stem Cell transplant (alloSCT) is a curative procedure for many blood disorders and involves the transplantation of donor blood cells into a compatible recipient.  Engraftment is a key milestone of success of alloSCT and is measured by standard blood tests to ensure normal levels of blood cells as well as a specialised blood test to confirm this blood is being produced by donor tissue. Poor graft function (PGF) is a significant complication of alloSCT and results in poor blood cell production by engrafted donor tissue. Aplastic anaemia(AA) is an autoimmune disease that results in the body's own immune cells attacking the bone marrow (the organ that produces blood cells) resulting in decreased production of blood cells. The mechanisms leading to  PGF and AA are similar. There is evidence that the bone marrow microenvironment, the ecosystem in which blood cells reside, is abnormal in both PGF and AA. Atorvastatin is an old drug that has been used to treat high cholestrol and N-acetyl-cysteine (NAC) has been used as an antioxidant to treat paracetamol overdose.  There is evidence that atorvastatin and NAC may be able to reverse this microenvironment dysfunction in PGF and AA. This study is aimed at testing the efficacy and safety of atorvastatin and NAC in the treatment of PGF and relapsed/refractory Aplastic anaemia.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof David Ritchie

Address

Department of Clinical Haematology and BMT service
Peter MacCallum Cancer Centre/ The Royal Melbourne Hospital
300 Grattan Street
Parkville
VIC 3050

Country

Australia

Phone

+61 3 93427000

Fax

david.ritchie@mh.org.au

Contact person for public queries

Name

Ashvind Prabahran

Address

Department of Clinical Haematology and BMT service
Peter MacCallum Cancer Centre/ The Royal Melbourne Hospital
300 Grattan Street
Parkville
VIC 3050

Country

Australia

Phone

+61 3 93427000

Fax

ashvind.prabahran@mh.org.au

Contact person for scientific queries

Name

Ashvind Prabahran

Address

Department of Clinical Haematology and BMT service
Peter MacCallum Cancer Centre/ The Royal Melbourne Hospital
300 Grattan Street
Parkville
VIC 3050

Country

Australia

Phone

+61 3 93427000

Fax

ashvind.prabahran@mh.org.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

Individual patient data that underline the results reported in any future publication after de-identification

When will data be available (start and end dates)?

Beginning 3 months and ending 5 years following article publication

Available to whom?

Researchers who provide a methologically sound proposal with ethics approval

Available for what types of analyses?

Any purpose

How or where can data be obtained?

Proposal will need to be directed to Dr Ashvind Prabahran via ashvind.prabahran@mh.org.au. Requestors will need to sing a data access agreement.

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
9532	Study protocol			ashvind.prabahran@mh.org.au

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.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically