Avatrombopag in untreated severe aplastic anaemia - a Bayesian optimal phase 2 study

Recruitment & Eligibility

Status: Active, not recruiting

Sex: All

Target Recruitment: 57

Inclusion Criteria

1.Severe or very severe aplastic anaemia characterised by bone marrow cellularity <30% (excluding lymphocytes) and at least two of the following:
a.Absolute neutrophil count <0.5 x10^9/L
b.Platelet count <20 x 10^9/L
c.Absolute reticulocyte count <60 x 10^9/L
2.No prior ATG-based immunosuppressive therapy
3.Age >18 years
4.Negative pregnancy test for women of child bearing potential

Exclusion Criteria

1.Planned for a sibling allogeneic stem cell transplant
2.Evidence of a myelodysplastic syndrome, defined according to the World Health Organization 2017 criteria. Patients with AA with cytogenetic abnormalities that are recurrent in MDS, who do not meet the WHO diagnostic criteria for MDS, are also excluded. Patients with del(20q), +8 and –Y are not included in this category and are therefore eligible for this trial.
3.Known diagnosis or clinical suspicion of inherited bone marrow failure syndrome (IBMFS), including but not limited to Fanconi Anaemia, Dyskeratosis Congenita, Shwachman-Diamond Syndrome and Diamond-Blackfan Anaemia
4.Previous history of stem cell transplantation
5.Cancer diagnosis within the last 5 years (except for patients with resected basal cell carcinoma or squamous cell carcinoma of the skin)
6.Previous history of melanoma
7.Pregnant or breast feeding patients2,3
8.Active CMV disease
9.Participants with known hypersensitivity to any of the component medications (avatrombopag, cyclosporine, horse or rabbit ATG)
10.Concurrent hepatic, renal or cardiac disease of such severity that it would in the investigator’s opinion, preclude the patient’s ability to tolerate protocol therapy
11.Death anticipated within 14 days

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary endpoint - efficacy<br>Rate of complete response (CR), defined as meeting all of the following:<br>Haemoglobin >10 g/dL, <br>Absolute neutrophils >1.0 x 10^9/L and <br>Platelets >100 x 10^9/L <br>Haematological Response will be assessed on Full blood Examination and reticulocyte count [ Haematological response at month 6];Primary endpoint - safety<br>The primary safety endpoint will be Acquired Clonal Evolution (ACE) at 6 months.<br>Clonal evolution will be defined as a new clonal cytogenetic abnormality or bone marrow characteristics consistent with myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML) (as defined by the World Health Organization classification of haematological malignancies 2016).<br>This information will be assessed from bone marrow biopsy reports[ ACE will be assessed at the 6 month visit after the treatment period]

Secondary Outcome Measures