Eltrombopag Combining Rituximab Versus Eltrombopag in the Management of Primary Immune Thrombocytopenia (ITP) in Adults

August 15, 2020 updated by: Zhang Lei, Institute of Hematology & Blood Diseases Hospital

A Multicenter, Randomized, Open-label Study To Compare The Efficacy And Safety Of Eltrombopag Combining Rituximab With Eltrombopag In Adult ITP Patients

This multicenter randomized, open-label study aimed to compare the efficacy and safety of eltrombopag combining rituximab with eltrombopag in China adult ITP patients .This study was be conducted in adult ITP patients who had not responded to or had relapsed after previous treatment of ITP, including first line therapy and /or splenectomy.

Study Overview

Detailed Description

The primary objective of this study was to evaluate the efficacy and safety of eltrombopag combining rituximab treating previously treated ITP patients compared to eltrombopag. The secondary objective was to evaluate the efficacy of eltrombopag combining rituximab in ITP patients with positive autoantibody compared to eltrombopag .In addition, health-related quality of life (HRQoL) measure was assessed in all participants.

224 eligible subjects were randomized to either eltrombopag combining rituximab or eltrombopag treatment in 1:1 ratio. 112 enrolled patients are randomly picked up to take eltrombopag combining with rituximab at the indicated dose. 112 enrolled patients are randomly picked up to take eltrombopag at the indicated dose.

The initial dose of eltrombopag administration was an oral 75 mg once daily in all participants .The dose of eltrombopag was adjusted according to the subject platelet count during the period from week 1 to week 24.

Subjects in eltrombopag combining rituximab treatment group received single dose infusion of rituximab 375 mg/m(2) within 14 days after enrollment.

Study Type

Interventional

Enrollment (Anticipated)

224

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

      • Tianjin, China
        • Recruiting
        • Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Signed written informed consent
  2. Age from 18 to 60 years old
  3. Diagnosed with ITP and have a platelet count of <30 ×10^9/L on Day 1 (or within 48 hours prior to dosing on Day 1).
  4. Patients who have no response or relapsed after splenectomy(at least more than 6 months). Or patients who have not been splenectomised and have either not responded to one or more prior therapies, or who have relapsed prior therapy.
  5. Subjects treated with previous therapy(including but not limited to corticosteroid, azathioprine, danazol, cyclosporin A, mycophenolate mofetil) must have been completed prior to randomization, or must not be increasing a dose after enrollment.
  6. No pre-existing cardiac disease within the last 3 months. No arrhythmia known to increase the risk of thrombolic events (e.g. atrial fibrillation), or patients with a Corrected QT interval (QTc) >450msec or QTc >480 for patients with a Bundle Branch Block.
  7. No pre-existing infection within the last 1 months(including but not limited to pulmonary infection)
  8. Laboratory tests for coagulation function showed that prothrombin time (PT/INR) and activated partial thromboplastin time (APTT) no exceed normal by more than 20%. No history of clotting disorder, other than ITP.
  9. White blood cell count, neutrophil absolute value, hemoglobin, within the reference range, with the following exceptions:

    • Hemoglobin: females and males 10.0 g/dl are eligible for inclusion,
    • Absolute neutrophil count (ANC) ≥1500/µL (1.5×109/L) is required for inclusion
  10. The following blood chemistry test result no exceed normal by more than 20%:alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatinine,serum albumin must not be below the lower limit of normal (LLN) by more than 10%.
  11. Subject is non-childbearing potential of childbearing potential and use acceptable methods of contraception throughout the study.
  12. Subjects fully understand and are able to comply with the requirements of the research protocol and are willing to complete the study as planned.

Exclusion Criteria:

  1. Patients with any prior history of arterial or venous thrombosis, and with following risk factors: cancer, Factor V Leiden, ATIII deficiency, antiphospholipid syndrome.
  2. Pregnant or lactating women;
  3. Subjects is currently receiving treatment with another study medication.
  4. Any laboratory or clinical evidence for HIV infection.
  5. Any clinical history for hepatitis C infection; chronic hepatitis B infection; or any evidence for active hepatitis at the time of subject screening. Laboratory test shows positive serology for Hepatitis C or Hepatitis B (HB). In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded.
  6. History of platelet aggregation that prevents reliable measurement of platelet counts.
  7. Any clinically relevant abnormality, other than ITP,which in the opinion of the investigator makes the subject unsuitable for participation in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: efficacy of eltrombopag combining rituximab

After enrollment,all subjects receive eltrombopag treatment,the initial dose of eltrombopag administration was an oral 75 mg once daily.Complete blood count including platelet count was done once a week.The dose of eltrombopag was adjusted according to the subject platelet count during the period from week 1 to week 24. If the platelet count >250×10^9/L, the eltrombopag will stop until the platelet count <30×10^9/L.

All subjects receive single dose infusion of rituximab 375 mg/m(2) within 14 days after enrollment.

Efficacy and safety will be evaluated at Week 4, Week 8, and Week 12.

After enrollment,all subjects receive eltrombopag treatment,the initial dose of eltrombopag administration was an oral 75 mg once daily.Complete blood count including platelet count was done once a week.The dose of eltrombopag was adjusted according to the subject platelet count during the period from week 1 to week 24. If the platelet count >250×10^9/L, the eltrombopag will stop until the platelet count <30×10^9/L.

All subjects receive single dose infusion of rituximab 375 mg/m(2) within 14 days after enrollment.

Efficacy and safety will be evaluated at Week 4, Week 8, and Week 12.

Other Names:
  • TPO-R agonist & anti-CD20 antibody
ACTIVE_COMPARATOR: efficacy of eltrombopag

After enrollment,all subjects receive eltrombopag treatment,the initial dose of eltrombopag administration was an oral 75 mg once daily.Complete blood count including platelet count was done once a week.The dose of eltrombopag was adjusted according to the subject platelet count during the period from week 1 to week 24. If the platelet count >250×10^9/L, the eltrombopag will stop until the platelet count <30×10^9/L.

Efficacy and safety will be evaluated at Week 4, Week 8, and Week 12.

After enrollment,all subjects receive eltrombopag treatment,the initial dose of eltrombopag administration was an oral 75 mg once daily.Complete blood count including platelet count was done once a week.The dose of eltrombopag was adjusted according to the subject platelet count during the period from week 1 to week 24. If the platelet count >250×10^9/L, the eltrombopag will stop until the platelet count <30×10^9/L.

Efficacy and safety will be evaluated at Week 4, Week 8, and Week 12.

Other Names:
  • TPO-R agonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment response
Time Frame: From the start of study treatment (Day 1) up to the end of week 12.
Number of participants achieving a platelet count >=30×10^9/L and at least doubling of the baseline count at Week 4, Week 8, and Week 12 .
From the start of study treatment (Day 1) up to the end of week 12.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Drug efficacy
Time Frame: From the start of study treatment (Day 1) up to the end of week 4, week 8 and week 12.
Number of participants achieving a platelet count >=30×10^9/L at week 4, week 8, and week 12 in ITP patients with positive autoantibody
From the start of study treatment (Day 1) up to the end of week 4, week 8 and week 12.
Long-term treatment response
Time Frame: From the start of study treatment (Day 1) up to the end of week 16, week 20 and week 24
Number of participants achieving a platelet count >=30×10^9/L at week 16, week 20, and week 24.
From the start of study treatment (Day 1) up to the end of week 16, week 20 and week 24
Time to Response
Time Frame: From the start of study treatment (Day 1) up to the end of week 24
Time to response is defined as time from the start of treatment to the first time of achieving a platelet count >=30×10^9/L and at least doubling of the baseline count during the whole 24 weeks.
From the start of study treatment (Day 1) up to the end of week 24
Duration of response
Time Frame: From the start of study treatment (Day 1) up to the end of week 24.
Total duration of time a participant had a platelet count >=30×10^9/L
From the start of study treatment (Day 1) up to the end of week 24.
Evaluation of effectiveness
Time Frame: From the start of study treatment (Day 1) up to the end of week 24.
Number of participants that reduced or discontinued baseline concomitant ITP medications during the whole 24 weeks.
From the start of study treatment (Day 1) up to the end of week 24.
Number of participants with clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale.
Time Frame: From the start of study treatment (Day 1) up to the end of week 24.
The WHO Bleeding Scale is a measure of bleeding severity with the following grades: grade 0 = no bleeding, grade 1= petechiae, grade 2= mild blood loss, grade 3 = gross blood loss, and grade 4 = debilitating blood loss.
From the start of study treatment (Day 1) up to the end of week 24.
Immune Thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ)
Time Frame: From the start of study treatment (Day 1) up to the end of week 24.
In all participants ,use ITP-PAQ to assess the HRQoL before and after treatment.
From the start of study treatment (Day 1) up to the end of week 24.
Functional Assessment of Chronic Illness Therapy fatigue subscale (FACIT-F)
Time Frame: From the start of study treatment (Day 1) up to the end of week 24.
In all participants ,use FACIT-F to assess the HRQoL before and after treatment.
From the start of study treatment (Day 1) up to the end of week 24.
Number of Participants with side effects of the drugs
Time Frame: From the start of study treatment (Day 1) up to the end of week 24.
Side effects of the drugs included fever, headache, serum disease,hypotension, rashes, infection liver injury, hypokalaemia, etc.
From the start of study treatment (Day 1) up to the end of week 24.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

August 10, 2020

Primary Completion (ANTICIPATED)

February 10, 2022

Study Completion (ANTICIPATED)

August 10, 2022

Study Registration Dates

First Submitted

August 12, 2020

First Submitted That Met QC Criteria

August 15, 2020

First Posted (ACTUAL)

August 19, 2020

Study Record Updates

Last Update Posted (ACTUAL)

August 19, 2020

Last Update Submitted That Met QC Criteria

August 15, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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