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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Cancer Treatment Induced Thrombocytopenia

Intervention / Treatment
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* Drug: rhTPO
* Drug: Control


Participation Criteria
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Eligibility Criteria
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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: With a previous history of bleeding. Chemotherapy regimens containing platinum, gemcitabine, cytarabine, anthracycline, etc. Combination regimens containing targeted or chemotherapy drugs which regularly result in thrombocytopenia. Thrombocytopenia caused by bone marrow infiltration of tumor cells. Eastern Cooperative Oncology Group (ECOG) score ≥2. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rhTPO<br>The study in a 2:1 randomization ratio (110 subjects to rhTPO). | Drug: rhTPO<br>* 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.<br>* Other names: TPIAO;|
| Other: Control<br>The study in a 2:1 randomization ratio (55 subjects to control group). | Drug: Control<br>* Non-rhTPO treatment<br>* Other names: No intervention;|

What is the study measuring?
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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 cTnT/cTnI |  | 1,3 and 6 months after initial treatment | 
| Changes in NT-proBNP |  | 1,3 and 6 months after initial treatment | 
| Changes in LVEF | LVEF will be assessed by echocardiography | 1,3 and 6 months after initial treatment | 
| Changes in neutrophile granulocyte count |  | during 3 cycles cancer treatment period(each cycle is 14, 21 or 28 days) | 
| Incidence of adverse events | treatment-related adverse events | from study start date to the end of follow-up, up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rhTPO, Prophylactic Treatment, Cancer Treatment Induced Thrombocytopenia, Treatment Induced Cardiac Injury