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

Status

Recruiting

Phases

Phase 1

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12620001339943

Acronym

RESELECT

Enrollment

Registered

2020-12-11

Start date

2021-09-28

Completion date

2022-12-31

Last updated

2021-11-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

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.

Interventions

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

Study design

Allocation

Non-randomised trial

Intervention model

Other

Primary purpose

Treatment

Masking

Open (masking not used)

Eligibility

Sex/Gender

All

Age

17 Years to No maximum

Healthy volunteers

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

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

Outcome results