None listed
Conditions
Brief summary
The aim of this study is to assess the effectiveness and safety of using Eltrombopag in patients with early refractory ITP. Early refractory ITP is when the ITP is not responding to standard therapy within 6 months of diagnosis. Eltrombopag is approved in Australia to treat severe chronic ITP however it is not approved for use in early refractory ITP. Personal experience provided by doctors who have used this medication indicate that as well as being effective in treating patients with chronic severe ITP, it might also be effective when treating patients in the earlier stages of ITP when initial steroid therapy is no longer adequately working. This is an open label study, all patients will receive an oral tablet dose daily of eltrombopag based on their platelet count and ethnicity (patients from Japan have been shown to have an increased eltrombopag serum level by approximately 80% compared to Caucasian patients). All patients will receive the study drug for 12 weeks and assessed for bleeding episodes and platelet count. Patients deemed to have responded will stay on eltrombopag with the opportunity to dose reduce to the lowest possible dose whilst maintaining a response over time. The study will run for 130 weeks (2 1/2 years) for those who continue to respond and there will be availability of the medication to patients beyond that. Overall response will be assessed at week 12 and defined as the achievement of CR, PR and MR. Time to response and duration of response and alternative treatment free survival will also be assessed. Therapeutic response will be assessed at week 26.
Interventions
This is an open label study, all patients will receive an oral tablet dose daily of eltrombopag based on their platelet
count and ethnicity (patients from Japan have been shown to have an increased eltrombopag serum level by
approximately 80% compared to Cuacasian patients). All patients will receive the study drug for 12 weeks and
assessed for bleeding episodes and platelet count. Patients deemed to have responded will stay on eltrombopag
with the opportunity to dose reduce to the lowest possib
This is an open label study, all patients will receive an oral tablet dose daily of eltrombopag based on their platelet count and ethnicity (patients from Japan have been shown to have an increased eltrombopag serum level by approximately 80% compared to Cuacasian patients). All patients will receive the study drug for 12 weeks and assessed for bleeding episodes and platelet count. Patients deemed to have responded will stay on eltrombopag with the opportunity to dose reduce to the lowest possible dose whilst maintaining a response over time. The study will run for 130 weeks (2 1/2 years) for those who continue to respond and the availability of the medication to patients beyond that. The starting dose of eltrombopag will depend on the patients platelet count. If the patient platelet count is less than 10 (x109/L) they will commence on Eltrombopag 75mg (or 50mg if they are of East Asian heritage) per day. If the platelet count is greater than 10 (x109/L) they will commence on Eltrombopag 50mg (or 25mg if of East Asian heritage) per day. This dose may be adjusted up to a maximum of Eltrombopag 150mg (or 100mg for patients of East Asian heritage) per day. Once the patient platelet count is stable the steroid dose and the eltrombopag dose is reduced to the lowest possible dose while maintaining acceptable platelet levels. All patients with early refractory ITP will remain on a minimum steroid dose of oral prednisolone 25mg daily for 2 weeks after the initiation of Eltrombopag. The prednisolone can be progressively weaned to zero over the subsequent 6 weeks if clinically appropriate. Patients with relapsed ITP will remain on Prednisolone, 10mg or less for 2 weeks after the initiation of Eltrombopag. The prednisolone can be progressively weaned to zero over the subsequent 6 weeks if clinically appropriate. Subsequent relapse of ITP to MR in this context in patients who have demonstrated steroid response in the past should be managed with resumption of prednisolone to a maximum of 10mg/day; dose escalation of Eltrombopag will only be considered in this context if MR is not achieved or there are steroid complications (e.g., unstable diabetes). Patients will be monitored weekly for the first 12 weeks and assessed for bleeding episodes and adverse events by physical examination and laboratory testing, inlcuding full blood counts. After this time patients deemed to have responded to treatment will be assess monthly. Patients will be expected to return unused or empty medication containers for drug accountability purposes.
Sponsors
Alfred Health
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
ALL of the following criteria must be met to be eligible: 1. Documented diagnosis of ITP (by exclusion) according to the ASH guidelines, 2. Age greater than or equal to 18 years, 3. Primary refractory ITP with a platelet count less than 30x109/L despite an average daily dose of at least 1mg/kg (or 75mg in patients greater than 75kg) prednisolone for at least 2 weeks OR Recurrent ITP after an initial response to steroids which requires 10mg or more of prednisolone per day and, or, recurrent doses of IVIG to maintain a platelet count of 30x109/L or greater (within 6 months of diagnosis, noting that above this threshold, steroid toxicity with prolonged therapy is unacceptable). 4. Failure of prior splenectomy will NOT be an inclusion criteria, noting that (a) splenectomy will not be appropriate in some patients due to surgical risk and (b) particularly in younger patients, avoiding splenectomy may be desirable if the natural history of acute ITP in a subset is ultimately to resolve Patients with ITP fulfilling the above criteria in the setting of HIV with CD4 count greater than 0.5x109/L undetectable viral load are eligible, as will be patients with secondary causes of ITP such as auto-immune disorders, lymphoproliferative disease and hepatitis C, subject to the exclusion criteria below.
Exclusion criteria
Patients presenting with any of the following will be excluded from the study: 1. Failure or inability to provide informed consent. 2. Geographic inaccessibility prohibiting follow-up. 3. Treatment with rituximab within 8 weeks prior to consent. 4. Predicted survival of less than 12 months. 5. Patients with multisystem autoimmune disease, lymphoproliferative disorders or hepatitis C anticipated who receive disease specific therapy within the first 12 weeks (e.g., chemotherapy, cyclophosphamide, anti-viral therapy) 6. Drug-induced thrombocytopenia. 7. Known hypersensitivity to thrombopoietin Receptor agonists. 8. Pregnant or breast-feeding. 9. Reproductive potential but not willing to adhere to adequate contraception from screening and for one year after first dose of Eltrombopag. 10. HIV with CD4 count less than 500 and detectable viral load. 11. Symptomatic clinical significant arterial or venous thrombosis within 6 weeks prior to consent. Note that patients requiring anti-platelet or anti-thrombotic therapy for an event prior to 6 weeks will be eligible, with the intention that this therapy will be resumed once the platelet count reaches an appropriate level (in the order of 50x109/L for most patients). However, patients at very high risk of thrombosis e.g., antiphospholipid syndrome with prior thromboses or multiple thrombophilia risk factors will not be eligible 12. Participation in another clinical trial with any investigational drug within 30 days prior to study screening.
Outcome results
None listed