Fixed Low-dose Eltrombopag and rhTPO for Immune Thrombocytopenia (FLOWER)

Immune Thrombocytopenia Clinical Trial

Official title:

Combination of Fixed Low-dose Eltrombopag and rhTPO for Treatment of Immune Thrombocytopenia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04518878
• Other study ID #: ITP-PKU019
• Status: Recruiting
• Phase: Phase 1
• Start date: August 31, 2020
• Est. completion date: June 2022

Study information

• Verified date: August 2020
• Source: Peking University People's Hospital
• Contact: Xiaohui Zhang, MD
• Phone: +86-13522338836
• Email: zhangxh100[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective, single-arm study to investigate the efficacy and safety of the combination of fixed low-dose eltrombopag plus recombinant human thrombopoietin (rhTPO) as treatment for corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) patients during the COVID-19 pandemic.

Description:

Eltrombopag, a small molecule agonist of thrombopoietin receptor (TPO-RA), was recommended as the subsequent treatment for ITP patients, which also already showed robust efficacy.Recombinant human thrombopoietin (rhTPO) is a full-length glycosylated-TPO produced by Chinese hamster ovary cells, which showed its effectiveness in ITP in a variety of studies.

Both eltrombopag and rhTPO demonstrated good safety in ITP patients. Because of their non-immunosuppressive nature, both of them serve as a reasonable choice during the global COVID-19 pandemic.

Since they increase the number of platelets through different mechanisms, and previous studies demonstrated that they might exert synergic effect. The investigators hypothesized that the combination of these two agents could be a promising option for treatment of corticosteroid-resistant or relapsed ITP patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: June 2022
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Clinically confirmed corticosteroid-resistant or relapsed immune thrombocytopenic purpura (ITP)

2. Subject has signed and provided written informed consent.

3. Fertile patients must use effective contraception during treatment and observational period

4. Negative pregnancy test

Exclusion Criteria:

1. Have an impaired renal function as indicated by a serum creatinine level > 2.0 mg/dL

2. Have an inadequate liver function as indicated by a total bilirubin level > 2.0 mg/dL and/or an aspartate aminotransaminase or alanine aminotransferase level > 3×upper limit of normal

3. Have a New York Heart Classification III or IV heart disease

4. Have a history of severe psychiatric disorder or are unable to comply with study and follow-up procedures

5. Have active hepatitis B or hepatitis C infection

6. Have a HIV infection

7. Have active infection requiring antibiotic therapy within 7 days prior to study entry

8. Are pregnant or lactating women, or plan to become pregnant or impregnated within 12 months of receiving study drug

9. Previous splenectomy

10. Had previous or concomitant malignant disease

11. Not willing to participate in the study.

12. Expected survival of < 2 years

13. Intolerant to murine antibodies

14. Immunosuppressive treatment within the last 2 weeks

15. Connective tissue disease

16. Autoimmune hemolytic anemia

17. Patients currently involved in another clinical trial with evaluation of drug treatment

Related Conditions & MeSH terms

• Immune Thrombocytopenia
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

Drug:
• Eltrombopag
Fixed dose of eltrombopag oral 25mg daily
• rhTPO
Rh-TPO 300U/kg subcutaneous injection once daily for 7 consecutive days, followed by a tapering dose in maintenance therapy.

Locations

Country	Name	City	State
China	Peking University Insititute of Hematology, Peking University People's Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response	A complete response (CR) was defined as a sustained (= 3 months) platelet count = 100×10^9/L.	6 weeks
Primary	Response	A response (R) was defined as a sustained (= 3 months) platelet count = 30×10^9/L without recurrence of thrombocytopenia.	6 weeks
Primary	No response	No response (NR) was defined as platelet count < 30 × 10^9/L or a less than two fold increase in platelet count from baseline or the presence of bleeding. Platelet count must be measured on two occasions more than a day apart.	6 weeks
Primary	Relapses	A relapses was defined as platelet count falls below 30×10^9/L or bleeding accrues after achieving R or CR.	6 weeks
Secondary	Early response	Early response was defined as the attainment of a platelet count = 30 × 10? and at least a doubling of baseline platelet count at 1 week.	7 days
Secondary	Initial response	Initial treatment was defined as the attainment of a platelet count = 30 × 10? and at least a doubling of baseline platelet count at 1 month.	1 month
Secondary	TOR (time to response)	The time to achieve platelet count = 30×10^9/L and at least 2-fold increase of the baseline count and absence of bleeding since start of treatment.	6 weeks
Secondary	DOR (duration of response)	The duration of achieve platelet count = 30×10^9/L and at least 2-fold increase of the baseline count and absence of bleeding since start of treatment.	6 weeks
Secondary	Treatments associated adverse events	All patients were assessed for safety every week during the first 8 weeks of treatment, and at 2-week intervals thereafter. Adverse events were scaled according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	6 weeks
Secondary	Reduction in bleeding symptoms	Changes of bleeding after treatment. Bleeding was defined in accordance with the WHO bleeding scale (0, no bleeding; 1, petechiae; 2, mild blood loss; 3, gross blood loss; and 4, debilitating blood loss).	6 weeks