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

• ClinicalTrials.gov Identifier: NCT04518878
• Recruitment Status: Unknown
• First Posted: August 19, 2020
• Last Update Posted: September 1, 2020
• Sponsor: Peking University People's Hospital
• Information provided by (Responsible Party): Xiao Hui Zhang, Peking University People's Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Immune Thrombocytopenia	Drug: Eltrombopag; Drug: rhTPO	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Combination of Fixed Low-dose Eltrombopag and rhTPO for Treatment of Immune Thrombocytopenia
• Actual Study Start Date: August 31, 2020
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: June 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Fixed Low-dose Eltrombopag and rhTPO; Fixed Low-dose Eltrombopag and rhTPO	Drug: Eltrombopag; Fixed dose of eltrombopag oral 25mg daily; Other Name: Revolade; Drug: rhTPO; Rh-TPO 300U/kg subcutaneous injection once daily for 7 consecutive days, followed by a tapering dose in maintenance therapy.; Other Name: TPIAO, tebiao

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Early response [ Time Frame: 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.
2. Initial response [ Time Frame: 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.
3. TOR (time to response) [ Time Frame: 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.
4. DOR (duration of response) [ Time Frame: 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.
5. Treatments associated adverse events [ Time Frame: 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.
6. Reduction in bleeding symptoms [ Time Frame: 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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Xiaohui Zhang, MD; +86-13522338836; zhangxh100@sina.com

Contact: Xuelin Dou, MD; +86-15510491556; dxldw@163.com

Locations

China, Beijing

Peking University Insititute of Hematology, Peking University People's Hospital; Recruiting

Beijing, Beijing, China, 100010

Contact: Xiaohui Zhang zhangxh100@sina.com

Sponsors and Collaborators

Peking University People's Hospital

Investigators

• Principal Investigator: Xiaohui Zhang, MD; Peking University People's Hospital, Peking University Insititute of Hematology

More Information

• Responsible Party: Xiao Hui Zhang, Vice president of Peking Univeristy Institute of Hematology, Peking University People's Hospital
• ClinicalTrials.gov Identifier: NCT04518878
• Other Study ID Numbers: ITP-PKU019
• First Posted: August 19, 2020
• Last Update Posted: September 1, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Xiao Hui Zhang, Peking University People's Hospital:

corticosteroid-resistant or relapsed ITP; eltrombopag; recombinant human thrombopoietin (rhTPO)

Additional relevant MeSH terms:

Thrombocytopenia; Purpura, Thrombocytopenic, Idiopathic; Blood Platelet Disorders; Hematologic Diseases; Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Thrombotic Microangiopathies; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Skin Manifestations