Back to resultsEltrombopag Combining Rituximab Versus Eltrombopag in the Management of Primary Immune Thrombocytopenia (ITP) in Adults
Primary Purpose
Primary Immune Thrombocytopenia (ITP)
Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
eltrombopag combining rituximab
eltrombopag
Sponsored by
About this trial
This is an interventional treatment trial for Primary Immune Thrombocytopenia (ITP) focused on measuring immune thrombocytopenia, autoantibody, eltrombopag, rituximab
Eligibility Criteria
Inclusion Criteria:
- Signed written informed consent
- Age from 18 to 60 years old
- 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).
- 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.
- 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.
- 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.
- No pre-existing infection within the last 1 months(including but not limited to pulmonary infection)
- 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.
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
- 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%.
- Subject is non-childbearing potential of childbearing potential and use acceptable methods of contraception throughout the study.
- 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:
- Patients with any prior history of arterial or venous thrombosis, and with following risk factors: cancer, Factor V Leiden, ATIII deficiency, antiphospholipid syndrome.
- Pregnant or lactating women;
- Subjects is currently receiving treatment with another study medication.
- Any laboratory or clinical evidence for HIV infection.
- 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.
- History of platelet aggregation that prevents reliable measurement of platelet counts.
- Any clinically relevant abnormality, other than ITP,which in the opinion of the investigator makes the subject unsuitable for participation in the study.
Sites / Locations
- Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
efficacy of eltrombopag combining rituximab
efficacy of eltrombopag
Arm Description
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. Efficacy and safety will be evaluated at Week 4, Week 8, and Week 12.
Outcomes
Primary Outcome Measures
Treatment response
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 .
Secondary Outcome Measures
Drug efficacy
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
Long-term treatment response
Number of participants achieving a platelet count >=30×10^9/L at week 16, week 20, and week 24.
Time to Response
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.
Duration of response
Total duration of time a participant had a platelet count >=30×10^9/L
Evaluation of effectiveness
Number of participants that reduced or discontinued baseline concomitant ITP medications during the whole 24 weeks.
Number of participants with clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale.
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.
Immune Thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ)
In all participants ,use ITP-PAQ to assess the HRQoL before and after treatment.
Functional Assessment of Chronic Illness Therapy fatigue subscale (FACIT-F)
In all participants ,use FACIT-F to assess the HRQoL before and after treatment.
Number of Participants with side effects of the drugs
Side effects of the drugs included fever, headache, serum disease,hypotension, rashes, infection liver injury, hypokalaemia, etc.
Full Information
NCT ID
NCT04518475
First Posted
August 12, 2020
Last Updated
August 15, 2020
Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Collaborators
The Second Affiliated Hospital of Kunming Medical University, Henan Cancer Hospital, Tianjin Medical University Second Hospital, The First Affiliated Hospital of Xiamen University, Nantong University
1. Study Identification
Unique Protocol Identification Number
NCT04518475
Brief Title
Eltrombopag Combining Rituximab Versus Eltrombopag in the Management of Primary Immune Thrombocytopenia (ITP) in Adults
Official Title
A Multicenter, Randomized, Open-label Study To Compare The Efficacy And Safety Of Eltrombopag Combining Rituximab With Eltrombopag In Adult ITP Patients
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Unknown status
Study Start Date
August 10, 2020 (Actual)
Primary Completion Date
February 10, 2022 (Anticipated)
Study Completion Date
August 10, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Collaborators
The Second Affiliated Hospital of Kunming Medical University, Henan Cancer Hospital, Tianjin Medical University Second Hospital, The First Affiliated Hospital of Xiamen University, Nantong University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Immune Thrombocytopenia (ITP)
Keywords
immune thrombocytopenia, autoantibody, eltrombopag, rituximab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
224 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
efficacy of eltrombopag combining rituximab
Arm Type
Experimental
Arm Description
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.
Arm Title
efficacy of eltrombopag
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
eltrombopag combining rituximab
Other Intervention Name(s)
TPO-R agonist & anti-CD20 antibody
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
eltrombopag
Other Intervention Name(s)
TPO-R agonist
Intervention Description
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.
Primary Outcome Measure Information:
Title
Treatment response
Description
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 .
Time Frame
From the start of study treatment (Day 1) up to the end of week 12.
Secondary Outcome Measure Information:
Title
Drug efficacy
Description
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
Time Frame
From the start of study treatment (Day 1) up to the end of week 4, week 8 and week 12.
Title
Long-term treatment response
Description
Number of participants achieving a platelet count >=30×10^9/L at week 16, week 20, and week 24.
Time Frame
From the start of study treatment (Day 1) up to the end of week 16, week 20 and week 24
Title
Time to Response
Description
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.
Time Frame
From the start of study treatment (Day 1) up to the end of week 24
Title
Duration of response
Description
Total duration of time a participant had a platelet count >=30×10^9/L
Time Frame
From the start of study treatment (Day 1) up to the end of week 24.
Title
Evaluation of effectiveness
Description
Number of participants that reduced or discontinued baseline concomitant ITP medications during the whole 24 weeks.
Time Frame
From the start of study treatment (Day 1) up to the end of week 24.
Title
Number of participants with clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale.
Description
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.
Time Frame
From the start of study treatment (Day 1) up to the end of week 24.
Title
Immune Thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ)
Description
In all participants ,use ITP-PAQ to assess the HRQoL before and after treatment.
Time Frame
From the start of study treatment (Day 1) up to the end of week 24.
Title
Functional Assessment of Chronic Illness Therapy fatigue subscale (FACIT-F)
Description
In all participants ,use FACIT-F to assess the HRQoL before and after treatment.
Time Frame
From the start of study treatment (Day 1) up to the end of week 24.
Title
Number of Participants with side effects of the drugs
Description
Side effects of the drugs included fever, headache, serum disease,hypotension, rashes, infection liver injury, hypokalaemia, etc.
Time Frame
From the start of study treatment (Day 1) up to the end of week 24.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed written informed consent
Age from 18 to 60 years old
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).
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.
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.
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.
No pre-existing infection within the last 1 months(including but not limited to pulmonary infection)
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.
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
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%.
Subject is non-childbearing potential of childbearing potential and use acceptable methods of contraception throughout the study.
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:
Patients with any prior history of arterial or venous thrombosis, and with following risk factors: cancer, Factor V Leiden, ATIII deficiency, antiphospholipid syndrome.
Pregnant or lactating women;
Subjects is currently receiving treatment with another study medication.
Any laboratory or clinical evidence for HIV infection.
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.
History of platelet aggregation that prevents reliable measurement of platelet counts.
Any clinically relevant abnormality, other than ITP,which in the opinion of the investigator makes the subject unsuitable for participation in the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lei Zhang
Phone
+86 13502118379
Email
zhanglei1@ihcams.ac.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lei Zhang, M.D., Ph.D
Organizational Affiliation
Institute of Hematology & Blood Diseases Hospital, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
City
Tianjin
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaofan Liu
Phone
+86 13752006059
Email
liuxiaofan@ihcams.ac.cn
First Name & Middle Initial & Last Name & Degree
Lei Zhang
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Eltrombopag Combining Rituximab Versus Eltrombopag in the Management of Primary Immune Thrombocytopenia (ITP) in Adults
We'll reach out to this number within 24 hrs