ITP - Immune Thrombocytopenia
Conditions
Keywords
ITP, thrombocytopenia, Avatrombopag, thrombopoietin receptor agonist
Brief summary
This is a single-center, open label pilot trial where patients with primary ITP who require second line treatment will be offered avatrombopag at a reduced starting dose, adjusted thereafter according to the response and continued for up to 24 weeks. The study aims to acquire experience on use of avatrombopag and explore the efficacy and safety of lower starting dose of avatrombopag
Detailed description
Avatrombopag is an oral thrombopoietin receptor agonist that is licensed for chronic ITP. Avatrombopag is administered at a starting dose of 20 mg daily. Overshooting of platelet count is a frequent problem that occurs in 20 to 40% of the patients after initiating avatrombopag as recommended. In this open label, single arm, pilot study, we will start avatrombopag at a reduced starting dose of 20 mg every other day. The dose will be adjusted thereafter according to the platelet response. The study consists of 3 phases: Dose adjustment phase, a maintenance phase, and dose tapering/disconsolation and follow-up phase. The study aims to acquire experience on use of avatrombopag and explore the efficacy and safety of lower starting avatrombopag-dose, and assess the rate of sustained response off-treatment. The duration of treatment with avatrombopag is 6 months. The study is an investigator-initiated trial sponsored by Center for Transplantation and Blood Diseases. Medical City Complex, Baghdad Iraq.
Interventions
Description: Patients will start on avatrombopag 20 mg every other day for a week then the dose will be readjusted according to the platelet count.
Sponsors
Al-Mustansiriyah University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female aged ≥18 years. 2. Diagnosis of primary ITP and having a platelet count of \< 30 x109/L measured within two weeks prior to inclusion with failure to achieve response or relapse after at least one cycle of dexamethasone (20-40 mg daily for 4 days) or prednisone /prednisolone (1 mg/kg for at least two weeks). Shorter courses or lower doses are allowed if discontinued or modified due to side effects. 3. Clinical need for second (subsequent) line treatment with a platelet elevating therapy assessed by the physician in charge. 4. Signed and dated written informed consent.
Exclusion criteria
1. Previous treatment with TPO-RA. 2. Pregnancy or lactation. 3. Patients with active serious bleeding or at high risk of bleeding as judged by physician in charge. 4. Females of child-bearing potential refusing to follow effective contraceptive methods (as described in SmPC) during treatment with Avatrombopag. 5. Secondary ITP defined as ITP secondary to lymphoma or chronic lymphocytic leukemia; ITP secondary to the following autoimmune disorders Systemic Lupus Erythematosus or Antiphospholipid Syndrome; ITP secondary to Common Variable Immune Deficiency; ITP secondary to the following viral infections eg Human Immunodeficiency Virus. 6. Concomitant autoimmune hemolytic anemia, Evans syndrome. 7. Presence of any serious comorbidity where the condition may worsen the study drugs. 8. Presence of active malignancy unless deemed cured by adequate treatment. Participants with the following neoplastic conditions can be included: * Monoclonal gammopathy of undetermined significance (MGUS) or monoclonal B lymphocytosis of undetermined significance (MBUS) * Basal/squamous cell carcinoma of the skin * Carcinoma in situ of the cervix * Carcinoma in situ of the breast * Incidental histological finding of prostate cancer (TNM stage T1a or T1b) 9. Patients with history of poor compliance or history of alcohol/drug abuse or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Response Time | 20 weeks | Median cumulative number of weeks with platelet count \>50 x 109/L from time of Avatrombopag initiation to end of week 20. A period of 2 week will be deducted after IVIG and 4 weeks after dexamethasone. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response by day 8 | 8 days | Number of patients achieving platelet count \> 50 x 109/L by day 8 without any rescue therapy during the 2 weeks prior to the blood sampling. |
| Rates of platelet overshoot. | 6 weeks | Number of episode with platelet count \> 200 and \>400 x 109/L during the first 6 weeks after the initiation of avatrombopag. |
| Durable response rate. | 20 weeks | Number of patients achieving 4 consecutive platelet counts \> 50 x 109/L between weeks 12 and 20 including the last count, without the use of rescue therapy, corticosteroids or any platelet elevating agent after week 6. |
| The rates of treatment failure. | 20 weeks | Occurrence of treatment failure is defined as: Discontinuation of Avatrombopag and switching to another platelet elevating agent between weeks 6 and 20 due to non-response or intolerance to Avatrombopag or administration of rescue therapy after week 6 and Thrombocytopenia (platelet count \<30 x 109/L), high risk of bleeding or intolerance to avatrombopag. |
| TTR | 20 weeks | Time from initiation of dose to first platelet count \> 50 x 109/L without any rescue therapy during the 2 weeks prior to the blood sampling. |
| The safety of treatment with Avatrombopag. | 52 weeks | Occurrence and severity of treatment emergent adverse events. Occurrence and severity of adverse events of special interest including arterial and venous thrombosis and bone marrow fibrosis (bone marrow biopsy showing MF2 or higher). |
| The changes in HRQoL during the study. | 20 weeks | Change in of SF-36 (v1) questionnaires from baseline to weeks 20. |
| The rates of Sustained Response Off-Treatment (SROT) at week 52. | 52 weeks | Occurrence of SROT defined as: A platelet count \> 30 x 109/L in all planned visits between the time of discontinuation of Avatrombopag and week 52 including week 52 and no administration of platelet elevating agent between weeks 20 and 52. |
| Bleeding complications during the study. | 52 weeks | Number and severity of WHO bleeding events. |
Countries
Iraq
Contacts
Primary ContactAlaa Alwan, MD
Outcome results
None listed