This is a prospective, randomized, open-label, active-controlled study to evaluate the efficacy and safety of Romiplostim N01 plus all-trans retinoic acid (ATRA) compared with Romiplostim N01 alone in adults with persistent isolated chemotherapy-induced thrombocytopenia (PICIT) after complete remission of selected gynecologic, breast, or lung solid tumors, including but not limited to non-small cell lung cancer (NSCLC), ovarian cancer, and breast cancer. Eligible participants will be randomized in a 1:1 ratio to receive Romiplostim N01 plus oral ATRA or Romiplostim N01 alone for 12 weeks, with follow-up through Week 24. The primary outcome is the overall platelet response rate at Week 12, defined as platelet count \>50 x 10\^9/L in at least 2 of the last 3 scheduled platelet assessments up to Week 12. Secondary outcomes include sustained response during Weeks 13 to 24, complete and partial response rates, duration of response, time to response, platelet count changes, platelet transfusion requirements, bleeding events, and safety.
Chemotherapy-induced thrombocytopenia is a clinically important complication of anticancer treatment. In some patients, thrombocytopenia persists after completion of chemotherapy despite complete remission of the underlying tumor. Persistent isolated chemotherapy-induced thrombocytopenia (PICIT) is characterized by prolonged thrombocytopenia with relatively preserved red blood cell and neutrophil counts, after exclusion of other causes of thrombocytopenia. This study focuses on adult patients with PICIT after complete remission of selected gynecologic, breast, or lung solid tumors, including but not limited to non-small cell lung cancer (NSCLC), ovarian cancer, and breast cancer. Other eligible tumor types may include endometrial cancer, cervical cancer, fallopian tube cancer, primary peritoneal cancer, and other lung cancers, if the participant otherwise meets the protocol-defined criteria. Romiplostim N01 is a thrombopoietin receptor agonist intended to stimulate megakaryocyte proliferation and platelet production. All-trans retinoic acid (ATRA) may provide additional hematopoietic and immunomodulatory effects. The study will compare Romiplostim N01 plus ATRA with Romiplostim N01 alone. Eligible participants will be centrally randomized in a 1:1 ratio to one of two treatment arms. Participants in the experimental arm will receive Romiplostim N01 by subcutaneous injection once weekly plus oral ATRA twice daily for 12 weeks. Participants in the active comparator arm will receive Romiplostim N01 alone once weekly for 12 weeks. Romiplostim N01 dose adjustment will be based on platelet count according to the protocol. Supportive care and rescue treatment, including platelet transfusion for severe bleeding or clinically indicated thrombocytopenia, are permitted. Participants will be followed weekly during Weeks 1 to 12 and every 2 weeks during Weeks 13 to 24. The primary endpoint is overall response rate at Week 12. Secondary endpoints include sustained response rate during Weeks 13 to 24, complete response rate, partial response rate, duration of response, time to response, platelet count changes, platelet transfusion requirements, bleeding events, and adverse events. Safety will be assessed by monitoring adverse events and serious adverse events, including ATRA-related toxicities and thrombopoietin receptor agonist-associated risks such as thromboembolic events.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
220
Romiplostim N01 will be administered by subcutaneous injection at an initial dose of 4 mcg/kg once weekly for 12 weeks. The dose may be adjusted according to platelet count: increase by 2 mcg/kg if platelet count is \<50 x 10\^9/L, with a maximum dose of 10 mcg/kg; maintain the current dose if platelet count is \>=50 to \<=200 x 10\^9/L; reduce by 1 mcg/kg if platelet count is \>200 to \<=400 x 10\^9/L; and withhold dosing if platelet count is \>400 x 10\^9/L, then restart at a lower dose after platelet count decreases to approximately 200 x 10\^9/L.
All-trans retinoic acid (ATRA) will be administered orally at 10 mg twice daily for 12 weeks. Dose interruption, reduction, or discontinuation may be performed for intolerable toxicity or clinically significant adverse events according to the protocol.
Peking University People's Hospital
Beijing, China
RECRUITINGOverall Platelet Response Rate at Week 12
Percentage of participants with platelet count \>50 x 10\^9/L in at least 2 of the last 3 scheduled platelet assessments up to Week 12. Platelet transfusion or other rescue/supportive treatment will not be counted as a platelet response.
Time frame: From randomization to Week 12
Sustained Platelet Response Rate During Weeks 13 to 24
Percentage of participants with platelet count \>50 x 10\^9/L in at least 2 of the last 3 scheduled platelet assessments during Weeks 13 to 24 and without rescue therapy during this period.
Time frame: Weeks 13 through 24
Complete Response Rate
Percentage of participants with platelet count \>=100 x 10\^9/L and no bleeding for at least 2 consecutive weeks.
Time frame: Up to Week 24
Partial Response Rate
Percentage of participants with platelet count \>=30 x 10\^9/L and at least 2 times the baseline platelet count, with no bleeding.
Time frame: Up to Week 24
Duration of Response
Among responders, time from first achievement of platelet response to platelet count \<30 x 10\^9/L or the end of study follow-up.
Time frame: From first documented response to Week 24
Time to Response
Time from treatment start to the first platelet count \>=30 x 10\^9/L.
Time frame: From treatment start to Week 24
Change in Platelet Count Over Time
Change in peripheral blood platelet count from baseline at scheduled study visits.
Time frame: Baseline; weekly during Weeks 1 to 12; every 2 weeks during Weeks 13 to 24
Platelet Transfusion Requirement
Frequency and total amount of platelet transfusions during treatment and follow-up.
Time frame: From treatment start to Week 24
Incidence of Bleeding Events
Percentage of participants with any bleeding event and severity of bleeding events recorded during the study.
Time frame: From treatment start to Week 24
Incidence of Adverse Events and Serious Adverse Events
Adverse events and serious adverse events will be recorded and graded according to CTCAE version 5.0 and summarized by treatment arm.
Time frame: From first dose to Week 24
Incidence of Thromboembolic Events
Percentage of participants with confirmed thromboembolic events during treatment and follow-up.
Time frame: From first dose to Week 24
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