Multi-target Drugs Sequential Combination Therapy in Adults Patients With Newly Diagnosed Primary Immune Thrombocytopenia
Efficacy and Safety of Multi-Target Drugs Sequential Combination Therapy in Adults Patients With Newly Diagnosed Primary Immune Thrombocytopenia: A Prospective, Single-arm, Multicenter, Exploratory Trial
This prospective, single-arm, multicenter, exploratory study will enroll 38 adults patients with newly diagnosed primary immune thrombocytopenia (ITP). Patients will receive standard-dose corticosteroids plus a thrombopoietin receptor agonist (TPO-RA) as initial therapy During the core treatment phase (Weeks 1-12). Corticosteroids will be tapered and discontinued within 8 weeks, whereas TPO-RA treatment will continue for 12 weeks. For patients with treatment failure( defined as platelet count < 30 × 10^9/L or less than 2-fold increase of baseline platelet count or bleeding) ,a sequential multitarget combination strategy will be explored in subsequent treatment phases. Specifically, patients with treatment failure after 2 weeks of initial therapy (Weeks 3-12), will receive the ongoing TPO-RA in combination with either rituximab or an anti-CD38 monoclonal antibody（mAb） as sequential combination therapy.
During the core treatment follow-up phase (24 weeks), patients with treatment failure will enter the exploratory treatment phase (Weeks 13-36) .
Patients who received multi-target drug therapy during the core treatment period will switch to an alternative TPO-RA with cross-administered rituximab and anti-CD38 mAb, while those who did not will receive sequential rituximab or anti-CD38 mAb.
Finally, patients will enter the safety follow up period (4 weeks, weeks 37-40).
연구 개요
상태
상세 설명
The study will be conducted in three phases.
Phase 1. Core treatment phase includes initial treatment and sequential combination therapy (12 weeks, weeks 1-12):
Patients will receive standard-dose methylprednisolone or prednisone in combination with a thrombopoietin receptor agonist (TPO-RA) as initial therapy.Corticosteroids will be tapered and discontinued within 8 weeks; tapering will begin immediately in patients who achieve complete response (CR) and will also be initiated after 4 weeks in patients who do not achieve response (R). TPO-RA therapy will continue for 12 weeks, with dose adjustments made according to the approved prescribing information. Patients with treatment failure( defined as platelet count < 30 × 10^9/L or less than 2-fold increase of baseline platelet count or bleeding) after 2 weeks of initial therapy (Weeks 3-12) will receive the ongoing TPO-RA in combination with either rituximab or an anti-CD38 monoclonal antibody as sequential combination therapy.
Phase 2. Core-treatment follow-up and exploratory treatment phase (24weeks, weeks 13-36):
During the core treatment follow-up phase, patients with treatment failure will enter the exploratory treatment phase. Patients who did not receive rituximab or anti-CD38 monoclonal antibody during the core treatment phase will receive a switched TPO-RA combined with either rituximab or anti-CD38 monoclonal antibody, whereas patients who received either rituximab or anti-CD38 monoclonal antibody during the core phase will receive a switched TPO-RA combined with cross-administered rituximab and anti-CD38 monoclonal antibody.TPO-RA therapy will also continue for 12 weeks.
Phase3. Safety follow-up phase (4weeks,weeks 37-40).
Rescue therapy includes, but is not limited to, intravenous immunoglobulin (IVIG), platelet transfusion, and vindesine. A switch to another thrombopoietin receptor agonist (TPO-RA) will be considered rescue therapy during the core treatment period. Administration of recombinant human thrombopoietin (rhTPO) will also be considered rescue therapy.
연구 유형
등록 (추정된)
단계
- 4단계
연락처 및 위치
연구 연락처
- 이름: Xiaofan Liu
- 전화번호: +86-022-23608180
- 이메일: liuxiaofan@ihcams.ac.cn
연구 연락처 백업
- 이름: Rongfeng Fu
- 이메일: furongfeng@ihcams.ac.cn
연구 장소
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Tianjin, 중국, 300020
- 모병
- Ethics Committee of Hematology Hospital, Chinese Academy of Medical Sciences
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연락하다:
- Shuo Chen
- 전화번호: +86-022-23608025
- 이메일: ec@ihcams.ac.cn
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참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
Inclusion Criteria:
- Age ≥18 years.
- Confirmed newly diagnosed primary ITP with a platelet count <30 × 10^9/L.
- No prior ITP-related treatment before enrollment, except for standard-dose corticosteroids and/or IVIG for ≤5 days.
- Able to understand the study and provide signed informed consent.-
Exclusion Criteria:
- Use of corticosteroids or immunosuppressants for a non-ITP condition within 3 months.
- Contraindication to corticosteroid therapy.
- Arterial or venous thromboembolic event within 3 months.
- Pregnant or breastfeeding women.
- Current treatment with another investigational drug.
Any other medical history or condition that, in the investigator's judgment, makes the participant unsuitable for the study.
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공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위화되지 않음
- 중재 모델: 순차적 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: Initial therapy
standard-dose corticosteroids plus a thrombopoietin receptor agonist (TPO-RA)
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Methylprednisolone 0.8-1mg/kg/day administered intravenously or orally; or prednisone 1 mg/kg/day, up to a maximum dose of 80 mg/day
Dosing will follow the recommended dose in the prescribing information; in severe ITP, the initial dose will be selected according to BAT (best available therapy) principles.
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실험적: Sequential Combination Therapy
the ongoing TPO-RA in combination with either rituximab or an anti-CD38 monoclonal antibody（mAb）
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Dosing will follow the recommended dose in the prescribing information; in severe ITP, the initial dose will be selected according to BAT (best available therapy) principles.
Administered as 375 mg/m² by intravenous infusion for a single dose, or 100 mg by intravenous infusion once weekly for a total of 4 doses.
Administered at 16 mg/kg by intravenous infusion once weekly for a total of 4-8 doses.
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실험적: Exploratory treatment
a switched TPO-RA combined with either rituximab or anti-CD38 monoclonal antibody
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Dosing will follow the recommended dose in the prescribing information; in severe ITP, the initial dose will be selected according to BAT (best available therapy) principles.
Administered as 375 mg/m² by intravenous infusion for a single dose, or 100 mg by intravenous infusion once weekly for a total of 4 doses.
Administered at 16 mg/kg by intravenous infusion once weekly for a total of 4-8 doses.
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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sustained response rate
기간: between weeks 13 and 36
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Defined as the proportion of patients who achieve a platelet count ≥30×10^9/L at least 6 out of 12 scheduled visits during the 24 weeks following the core treatment period (weeks 13-36), in the absence of rescue therapy
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between weeks 13 and 36
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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time to response
기간: in 0-12 weeks
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The time from treatment initiation to achieve a complete response(platelet count ≥100 × 109/L and absence of bleeding) or a partial response(platelet count ≥30 × 10^9/L and at least 2-fold increase of the baseline platelet count and absence of bleeding)
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in 0-12 weeks
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Early response.
기간: at 1 week
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Proportion of patients achieving platelet count ≥30 × 10^9/L and at least doubling baseline at 1 week after treatment initiation.
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at 1 week
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Initial response
기간: at 1 month
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Proportion of patients achieving platelet count ≥30 × 10^9/L and at least doubling baseline at 1 month after treatment initiation.
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at 1 month
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overall response(OR) rate at week 12
기간: at week 12
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Proportion of patients achieving complete response (CR) plus response (R) at Week 12
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at week 12
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Proportion of patients requiring rescue therapy
기간: in 0-36 weeks
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in 0-36 weeks
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bleeding scores
기간: in 0-40 weeks
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Assessed according to the WHO Bleeding Scale and the ITP Bleeding Scale
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in 0-40 weeks
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Immune Thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ)
기간: in 0-40 weeks
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In all participants ,use ITP-PAQ to assess the HRQoL before and after treatment.
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in 0-40 weeks
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Functional Assessment of 36-Item Short Form Survey (SF-36) scale
기간: in 0-40 weeks
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In all participants ,use SF-36 scale to assess the HRQoL before and after treatment.
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in 0-40 weeks
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공동 작업자 및 조사자
수사관
- 연구 책임자: Lei Zhang, Thrombosis and Haemostasis Diagnosis Treatment Center
간행물 및 유용한 링크
일반 간행물
- Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N, Godeau B, Lechner K, Mazzucconi MG, McMillan R, Sanz MA, Imbach P, Blanchette V, Kuhne T, Ruggeri M, George JN. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009 Mar 12;113(11):2386-93. doi: 10.1182/blood-2008-07-162503. Epub 2008 Nov 12.
- Gudbrandsdottir S, Birgens HS, Frederiksen H, Jensen BA, Jensen MK, Kjeldsen L, Klausen TW, Larsen H, Mourits-Andersen HT, Nielsen CH, Nielsen OJ, Plesner T, Pulczynski S, Rasmussen IH, Ronnov-Jessen D, Hasselbalch HC. Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia. Blood. 2013 Mar 14;121(11):1976-81. doi: 10.1182/blood-2012-09-455691. Epub 2013 Jan 4.
- Provan D, Arnold DM, Bussel JB, Chong BH, Cooper N, Gernsheimer T, Ghanima W, Godeau B, Gonzalez-Lopez TJ, Grainger J, Hou M, Kruse C, McDonald V, Michel M, Newland AC, Pavord S, Rodeghiero F, Scully M, Tomiyama Y, Wong RS, Zaja F, Kuter DJ. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019 Nov 26;3(22):3780-3817. doi: 10.1182/bloodadvances.2019000812.
- Neunert C, Terrell DR, Arnold DM, Buchanan G, Cines DB, Cooper N, Cuker A, Despotovic JM, George JN, Grace RF, Kuhne T, Kuter DJ, Lim W, McCrae KR, Pruitt B, Shimanek H, Vesely SK. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019 Dec 10;3(23):3829-3866. doi: 10.1182/bloodadvances.2019000966.
- Chen Y, Xu Y, Li H, Sun T, Cao X, Wang Y, Xue F, Liu W, Liu X, Dong H, Fu R, Dai X, Wang W, Ma Y, Song Z, Chi Y, Ju M, Gu W, Pei X, Yang R, Zhang L. A Novel Anti-CD38 Monoclonal Antibody for Treating Immune Thrombocytopenia. N Engl J Med. 2024 Jun 20;390(23):2178-2190. doi: 10.1056/NEJMoa2400409.
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
- 혈구감소증
- 병리학적 과정
- 자가면역질환
- 면역계 질환
- 출혈
- 피부 증상
- 혈액 질환
- 혈액 응고 장애
- 출혈성 장애
- 혈소판 장애
- 혈전성 미세혈관병증
- 자반병, 혈소판감소증
- 퍼푸라
- 혈소판감소증
- 병리학적 상태, 징후 및 증상
- 징후 및 증상
- 헴 및 림프병
- 자반병, 혈소판감소증, 특발성
- 아미노산, 펩티드 및 단백질
- 단백질
- 다 환식 화합물
- 항체, 모노클로 날
- 항체
- 면역 글로불린
- 면역 단백질
- 혈액 단백질
- 혈청 글로불린
- 글로불린
- Pretadienes
- 임신
- 스테로이드
- 융합 링 화합물
- Pregnadienetriols
- Pregnadienediols
- 항체, 모노클로 날, 뮤린 유래
- 프레드니솔론
- 리툭시맙
- 프레드니손
- 메틸프레드니솔론
- 엘 트롬 보그
- 다라 토무 맙
기타 연구 ID 번호
- IIT2025106
- Investigator-Initiated Trial (기타 보조금/기금 번호: Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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