Clinical trial NCT04600960: Eltrombopag for Chemotherapy-induced Thrombocytopenia
Official title: Eltrombopag for Chemotherapy-induced Thrombocytopenia: a Prospective Multi-center One-arm Study in Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chemotherapy-induced Thrombocytopenia
Eltrombopag
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: Tianjin Medical University Cancer Institute and Hospital
name: Tianjin Medical University Second Hospital
name: Tianjin Third Central Hospital
name: Tianjin People's Hospital
name: Henan Cancer Hospital
name: The Second Affiliated Hospital of Kunming Medical University
First posted: 2020-10-23
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy and safety of eltrombopag to treat chemotherapy-induced thrombocytopenia in solid tumors

Detailed description: This is a single-arm study to evaluate the safety and efficacy of eltrombopag to treat chemotherapy-induced thrombocytopenia（CIT）. These subjects have been treated with recombinant human thrombopoietin（rhTPO） or interleukin 11（IL-11） before, the platelets can rise to normal or reach the effective standard, but after the re-application, the effective standard is not reached, or the effective standard is still not reached after the rhTPO 300U/kg/d treatment for 14 days. The investigator will assess the changes of the platelet counts after the treatment of eltrombopag from week 1 to week 24, and observe incidence of adverse events during the treatment of eltrombopag.The investigator will complete the 4 weeks safety visits（once a week），if the subjects end or withdraw from the clinical trial.

Patients with chemotherapy-induced thrombocytopenia who had the same inclusion and exclusion criteria in the same period or in the past will be compared with the efficacy and safety of supportive treatment in the same period or history, so as to preliminarily explore and evaluate the efficacy and safety of eltrombopag treatment.

Eligibility criteria: Inclusion Criteria:

* Aged ≥18 years old, male or female;
* Conform to the diagnostic criteria of chemotherapy-induced thrombocytopenia (CIT); Ineffective after repeated treatment with rhTPO or IL-11；
* Stop radiotherapy or chemotherapy for more than 1 month;
* Platelet counts \<30 ×10\^9/L, and bleeding tendency;
* Estimated survival period ≥ 6 months；
* People who are willing to sign the informed consent voluntarily and follow the research program.
* Liver and kidney function\<1.5×upper limit of normal, qualified for physical examination；
* Subject is practicing an acceptable method of contraception. Women of childbearing potential must have a negative serum pregnancy test in the whole study;

Exclusion Criteria:

* Those with uncontrollable primary diseases of important organs, such as extensive metastasis of malignant tumors, liver failure, heart failure, kidney failure and other diseases；
* Patients with poor compliance;
* Positive serology for HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), and/or hepatitis D virus (HDV), Syphilis; Positive for Epstein-Barr Virus DNA, Cytomegalovirus DNA;
* Accompanied by extensive and severe bleeding, such as hemoptysis, upper gastrointestinal bleeding, intracranial hemorrhage, etc.
* There is currently a heart disease requiring treatment or a poorly controlled hypertension judged by the investigator；
* Patients with thrombotic diseases such as pulmonary embolism, thrombosis, and atherosclerosis；
* Those who have received allogeneic stem cell transplantation or organ transplantation in the past；
* Patients with mental disorders who cannot normally obtain informed consent and undergo trials and follow-up；
* Patients whose toxic symptoms caused by treatment before participating in the trial have not disappeared；
* Other serious diseases that may restrict participants from participating in this trial (such as diabetes; severe heart failure; myocardial obstruction or unstable arrhythmia or unstable angina in the past 6 months; gastric ulcers; mobility Autoimmune diseases, etc.)；
* Patients with sepsis or patients with other irregular bleeding；
* Patients taking antiplatelet drugs at the same time；
* Pregnant women, suspected pregnancy (a positive pregnancy test for human chorionic gonadotropin in urine at screening) and breastfeeding patients；
* Pre-existing cardiac disease, including congestive heart failure of New York Heart Association \[NYHA\] Grade III/IV, arrhythmia requiring treatment or myocardial infarction within the last 6 months. No arrhythmia known to increase the risk of thrombotic events (e.g. atrial fibrillation), or patients with a QT \>450msec or QTc \> 480 for patients with a Bundle Branch Block;
* Researchers believe that patients should not participate in the test of any other condition.

Primary outcomes:
measure: Changes of the platelet counts after the treatment of eltrombopag
timeFrame: 24 weeks
measure: Incidence of adverse events after the treatment of eltrombopag
timeFrame: 24 weeks
Secondary outcomes:
measure: Changes of concentration of TPO in peripheral blood
timeFrame: 24 weeks
measure: Changes of concentration of TPO antibodies in peripheral blood
timeFrame: 24 weeks
measure: Changes of concentration of anti-c-Mpl antibodies in peripheral blood
timeFrame: 24 weeks
measure: Changes of concentration of TPO neutralizing antibodies in peripheral blood
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Chinese Academy of Medical Science and Blood Disease Hospital
state: Tianjin
Study officials:
affiliation: Chinese Academy of Medical Science and Blood Disease Hospital
name: Lei Zhanglei, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Winer ES, Safran H, Karaszewska B, Richards DA, Hartner L, Forget F, Ramlau R, Kumar K, Mayer B, Johnson BM, Messam CA, Mostafa Kamel Y. Eltrombopag with gemcitabine-based chemotherapy in patients with advanced solid tumors: a randomized phase I study. Cancer Med. 2015 Jan;4(1):16-26. doi: 10.1002/cam4.326. Epub 2014 Aug 28.
citation: Winer ES, Safran H, Karaszewska B, Bauer S, Khan D, Doerfel S, Burgess P, Kalambakas S, Mostafa Kamel Y, Forget F. Eltrombopag for thrombocytopenia in patients with advanced solid tumors receiving gemcitabine-based chemotherapy: a randomized, placebo-controlled phase 2 study. Int J Hematol. 2017 Dec;106(6):765-776. doi: 10.1007/s12185-017-2319-9. Epub 2017 Sep 1.