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

Phase 1

• Conditions: Immune Thrombocytopenia
• Interventions: Drug: Eltrombopag; Drug: rhTPO

• Registration Number: NCT04518878
• Lead Sponsor: Peking University People's Hospital

Brief 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.

Detailed 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.

Study Timeline

• Status Verified: 2020-08
• Study First Submitted: 2020-08-16
• Study First Submitted QC: 2020-08-16
• Study First Posted: 2020-08-19
• Study Start: 2020-08-31
• Last Update Submitted: 2020-08-31
• Last Update Posted: 2020-09-01
• Primary Completion: 2021-12
• Study Completion: 2022-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fixed Low-dose Eltrombopag and rhTPO	Eltrombopag	Fixed Low-dose Eltrombopag and rhTPO
Fixed Low-dose Eltrombopag and rhTPO	rhTPO	Fixed Low-dose Eltrombopag and rhTPO

Primary Outcome Measures

Name	Time	Method
Response	6 weeks	A response (R) was defined as a sustained (≥ 3 months) platelet count ≥ 30×10\^9/L without recurrence of thrombocytopenia.
Relapses	6 weeks	A relapses was defined as platelet count falls below 30×10\^9/L or bleeding accrues after achieving R or CR.
Complete response	6 weeks	A complete response (CR) was defined as a sustained (≥ 3 months) platelet count ≥ 100×10\^9/L.
No response	6 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Reduction in bleeding symptoms	6 weeks	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).
Early response	7 days	Early response was defined as the attainment of a platelet count ≥ 30 × 10⁹ and at least a doubling of baseline platelet count at 1 week.
Initial response	1 month	Initial treatment was defined as the attainment of a platelet count ≥ 30 × 10⁹ and at least a doubling of baseline platelet count at 1 month.
TOR (time to response)	6 weeks	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.
DOR (duration of response)	6 weeks	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.
Treatments associated adverse events	6 weeks	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.

Trial Locations

Locations (1)

Peking University Insititute of Hematology, Peking University People's Hospital; 🇨🇳 Beijing, Beijing, China