Efficacy and Safety of rhTPO's Prophylactic Treatment of CTIT in Patients With High Risk of Cardiac Injury (Circular)

A Multicenter Randomized Controlled Study to Assess the Efficacy and Safety of rhTPO's Prophylactic Treatment of Cancer Treatment-induced Thrombocytopenia in Patients With High Risk of Treatment-induced Cardiac Injury

To assess the efficacy and safety of an optimised dosing regimen of rhTPO's prophylactic treatment of cancer treatment-induced thrombocytopenia(CTIT) and to explore the cardioprotective effect of rhTPO in cancer patients with high risk of treatment-induced cardiac injury.

Study Overview

• Status: Recruiting
• Conditions: Cancer Treatment Induced Thrombocytopenia
• Intervention / Treatment: Drug: Control; Drug: rhTPO

Detailed Description

This is an open-label prospective randomized multicenter study of rhTPO's prophylactic treatment of CTIT in patients receiving chemotherapy at high risk of cardiac injury. Adult cancer patients with high risk of cancer treatment-induced thrombocytopenia and cardiac injury were enrolled. Patients will be randomised into the rhTPO treatment group or non-rhTPO treatment group with a 2:1 ratio. The patients in rhTPO group will receive rhTPO 300U/kg/d subcutaneous injection for 5 days per cycle and total 3 cycles. The primary endpoint is to observe the improvement of platelet count by rhTPO during 3 cycles treatment period.

• Study Type: Interventional
• Enrollment (Estimated): 165
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jiwei Liu, MD; Phone Number: 18098877966; Email: jiweiliudl@126.com
• Study Contact Backup: Name: Fengqi Fang, MD; Phone Number: 18098876723; Email: ffqlj@163.com

Study Locations

• China
  • Anhui
    • Anqing, Anhui, China, 246003
      • Recruiting
      • Anqing Municipal Hospital
      • Contact: Chenghui Li; Phone Number: 15856555363
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • Chinese PLA General Hospital
      • Contact: Xuechun Lu; Phone Number: 13241892863
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences
      • Contact: Shengyu Zhou; Phone Number: 13520852899
    • Beijing, Beijing, China, 100144
      • Recruiting
      • Peking University Shougang Hospital
      • Contact: Xiaodong Wang; Phone Number: 010-57830282
    • Beijing, Beijing, China, 100122
      • Recruiting
      • Beijing Chaoyang District Sanhuan Cancer Hospital
      • Contact: Lijie Zuo; Email: zuolijie@163.com
  • Hebei
    • Shijiazhuang, Hebei, China, 050011
      • Not yet recruiting
      • The Fourth Hospital of Hebei Medical University
      • Contact: Jian Shi; Phone Number: 13831110729
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Recruiting
      • Henan Cancer Hospital
      • Contact: Jufeng Wang; Phone Number: 13783583966
    • Zhengzhou, Henan, China, 450003
      • Recruiting
      • Henan Provincial People's Hospital
      • Contact: Shundong Cang; Phone Number: 13592675836
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Not yet recruiting
      • Tongji Hospital Tongji Medical College of Huazhong University of Science & Technology
      • Contact: Yongsheng Jiang; Phone Number: 15327434928
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Union Hospital Tongji Medical College, Huazhong University Of Science And Technology
      • Contact: Gang Wu; Phone Number: 13871240042
  • Jiangsu
    • Nanyang, Jiangsu, China, 226001
      • Recruiting
      • Affiliated Tumor Hospital of Nantong University
      • Contact: Lei Yang; Phone Number: 15851398092; Email: 1341320416@qq.com
  • Liaoning
    • Dalian, Liaoning, China, 116011
      • Recruiting
      • The First Affiliated Hospital of Dalian Medical University
      • Contact: Fengqi Fang; Phone Number: 18098876723; Email: ffqlj@163.com
      • Contact: Jiwei Liu; Phone Number: 18098877966; Email: jiweiliudl@126.com
    • Shenyang, Liaoning, China, 110801
      • Recruiting
      • Liaoning Cancer Hospital & Institute
      • Contact: Tao Sun; Phone Number: 18900917877
  • Shaanxi
    • Xi'an, Shaanxi, China, 710065
      • Recruiting
      • Shaanxi Provincial Cancer Hospital
      • Contact: Guoqing Wang; Phone Number: 13892828647
  • Tianjin
    • Tianjin, Tianjin, China, 300181
      • Recruiting
      • Tianjin Medical University Cancer Institute and Hospital
      • Contact: Huilai Zhang; Phone Number: 18622221228

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males or females greater than or equal to 18 years of age at signing of the informed consent.

• Patients clinically judged to be at high risk of CTIT: Patients who had a platelet count below 50×10^9/L in the past 3 months; or patients who meet the criteria for prophylactic treatment in the Chinese Expert Consensus on the Management of Thrombocytopenia due to Oncology Chemotherapy (2018 Edition).The criteria for prophylactic treatment include: 1) The nadir platelet value in the last chemotherapy cycle was <50×10^9/L；Or 2)The patients with nadir platelet value ≥50×10^9/L and <75×10^9/L in the previous chemotherapy cycle also met at least one of the following risk factors for bleeding:

  1. With a previous history of bleeding.
  2. Chemotherapy regimens containing platinum, gemcitabine, cytarabine, anthracycline, etc.
  3. Combination regimens containing targeted or chemotherapy drugs which regularly result in thrombocytopenia.
  4. Thrombocytopenia caused by bone marrow infiltration of tumor cells.
  5. Eastern Cooperative Oncology Group (ECOG) score ≥2.
  6. Previous radiotherapy or ongoing radiotherapy, especially for long and flat bones (e.g. pelvis, sternum, etc.).
• Platelet count ≥75×10^9/L and <150×10^9/L, Hemoglobin ≥9.0 g/dL and absolute neutrophils ≥1.5×10^9 /L during screening.
• Patients with medium and high-risk with cardiotoxicity risk score (CRS) ≥3 and ECOG score of 0, 1, or 2 during screening.
• The current tumor treatment belongs to the scope of neoadjuvant, adjuvant, relapsed metastatic/advanced first-line and second-line therapies, anticipated to receive at least 2 cycles of current regimen with survival ≥ 6 months. The regimens may be 14-day, 21-day or 28-day cycles combined with targeted, immunotherapy, etc.
• Inclusion of organ tumours and lymphomas, with no restriction on the type and stage of organ tumours, etc.
• Patient provided signed informed consent

Exclusion Criteria:

• Patients with severe cerebrovascular disease (including but not limited to stroke, cerebrovascular accident, etc.) or serious heart disease (such as heart valve disease, arrhythmia, myocardial infarction, congenital heart disease, cardiomyopathy, heart failure, etc.) within the 3 months.
• Previous thrombocytopenia caused by non-oncology chemotherapy drugs within 6 months, including but not limited to primary immune thrombocytopenia, EDTA-dependent pseudo-thrombocytopenia, hypersplenism, etc.
• Patients with blood dysplasia-related diseases such as aplastic anemia, myeloproliferative diseases, multiple myeloma, myelodysplastic syndromes, etc.
• Patients with any arterial and venous thrombotic events within the past 6 months；
• Patients who had agents that increase platelet production or transfusion of platelets within the past 1 month.

• Abnormal liver function:

  • Patients without liver metastasis: ALT/AST > 3ULN (upper limit of normal value) and TBIL > 3ULN.
  • Patients with liver metastasis: ALT/AST≥5ULN, TBIL≥5ULN.
• Abnormal renal function: Scr≥1.5ULN or eGFR≤60ml/min.
• Patients with uncontrolled serious infection;
• Pregnant women or those planning to have children during the study period and breastfeeding patients.
• Any condition that the investigator considers inappropriate for inclusion in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rhTPO; The study in a 2:1 randomization ratio (110 subjects to rhTPO).	Drug: rhTPO; rhTPO 300U/kg/d QD, subcutaneous injection applied for 5 days per cycle, total 3 cycles. If the patient's platelet count showed a trend of continuous decline and/or was accompanied by the risk of bleeding during the treatment or after the completion of 5 doses of rhTPO, the investigator judged that rhTPO should be continued for treatment, and rhTPO could be administered subcutaneously at 300U/kg/ day for a maximum of 14 doses per cycle. Discontinue when the absolute platelet count increases by ≥50×10^9/L or when the platelet count rises to ≥250×10^9/L.; Other Names: Recombinant human thrombopoietin; TPIAO
Other: Control; The study in a 2:1 randomization ratio (55 subjects to control group).	Drug: Control; Non-rhTPO treatment; Other Names: No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients whose platelet count is ≥ 75×10^9/L after 2 cycles cancer treatment.	Efficacy was defined as treatment without salvage therapy to increase platelet counts.	After 2 cycles cancer treatment (month 1.5~month 2, depends on chemotherapy regimen), each cycle is 14, 21 or 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients receiving salvage treatment to increase platelet counts.	Salvage treatment including platelet infusion, rhIL-11, etc.	during 3 cycles cancer treatment period(each cycle is 14, 21 or 28 days)
Changes in neutrophile granulocyte count		during 3 cycles cancer treatment period(each cycle is 14, 21 or 28 days)
Changes in cTnT/cTnI		1 and 3 months after initial treatment
Changes in NT-proBNP		1 and 3 months after initial treatment
Changes in LVEF	LVEF will be assessed by echocardiography	1 and 3 months after initial treatment
Incidence of adverse events	treatment-related adverse events	from study start date to the end of follow-up, up to 3 months

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Dalian Medical University
• Collaborators: Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Chinese PLA General Hospital; Henan Cancer Hospital; Tongji Hospital; Peking University Shougang Hospital; Tianjin Medical University Cancer Institute and Hospital; Shanxi Provincial Cancer Hospital; Henan Provincial People's Hospital; Wuhan Union Hospital, China; Hebei Medical University Fourth Hospital; Liaoning Tumor Hospital & Institute; Anqing Municipal Hospital; The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province, China; Bethune Charitable Foundation; Beijing Sanhuan Cancer Hospital
• Investigators: Principal Investigator: Yunlong Xia, MD,PhD, The First Affiliated Hospital of Dalian Medical University

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2022
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: May 26, 2022
• First Submitted That Met QC Criteria: June 6, 2022
• First Posted (Actual): June 9, 2022

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 29, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: rhTPO; Prophylactic Treatment; Cancer Treatment Induced Thrombocytopenia; Treatment Induced Cardiac Injury
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Platelet Disorders; Thrombocytopenia
• Other Study ID Numbers: FJ-KS-KY-2022-28(X)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Researchers qualified can request the dataset, including de-identified individual subject data. Data may be requested from PI from 12 months 36 months after study completion.
• IPD Sharing Time Frame: From 12 months 36 months after study completion.
• IPD Sharing Access Criteria: Upon request to PI.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No