Persistent Isolated Chemotherapy-Induced Thrombocytopenia, Chemotherapy-Induced Thrombocytopenia, Gynecologic Cancers, Ovarian Cancer, Breast Cancer, Lung Cancer, Non-Small Cell Lung Cancer, Cervical Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer
Conditions
Keywords
PICIT, Persistent isolated chemotherapy-induced thrombocytopenia, CIT, Chemotherapy-induced thrombocytopenia, Romiplostim N01, ATRA, All-trans retinoic acid, Tretinoin, Thrombopoietin receptor agonist, Gynecologic cancer, Ovarian cancer, Breast cancer, Lung cancer, NSCLC, Non-small cell lung cancer, Endometrial cancer, Cervical cancer, Complete remission, Platelet response, Thrombocytopenia, Primary Peritoneal Cancer, Fallopian Tube Cancer
Brief summary
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.
Detailed description
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.
Interventions
DRUGRomiplostim N01
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.
DRUGAll-trans retinoic acid
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.
Sponsors
Peking University People's Hospital
Peking University Cancer Hospital and Institute
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Peking University International Hospital
Shanxi Province Cancer Hospital
Henan Provincial People's Hospital
China-Japan Union Hospital, Sun Yat-sen University Cancer Center
Hebei Medical University Fourth Hospital
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Eligible adult participants with persistent isolated chemotherapy-induced thrombocytopenia after complete remission of selected gynecologic, breast, or lung solid tumors will be randomized in a 1:1 ratio to receive either Romiplostim N01 plus ATRA or Romiplostim N01 alone. Treatment will continue for 12 weeks, followed by observation through Week 24. Randomization will be stratified by tumor category, such as NSCLC/lung cancer, ovarian or other gynecologic cancer, and breast cancer, as specified in the statistical analysis plan.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years or older. 2. Prior diagnosis of a selected gynecologic, breast, or lung solid tumor, including but not limited to non-small cell lung cancer (NSCLC), ovarian cancer, or breast cancer. Other eligible tumor types may include endometrial cancer, cervical cancer, fallopian tube cancer, primary peritoneal cancer, and other lung cancers, if clinically appropriate and if all other eligibility criteria are met. 3. Complete remission of the underlying tumor after chemotherapy or antitumor treatment, with tumor-related treatment discontinued for at least 12 weeks before enrollment, no evidence of recurrence or progression by specialist assessment, and no current need for additional tumor-directed therapy. 4. Persistent isolated chemotherapy-induced thrombocytopenia, defined as platelet count \<30 x 10\^9/L on two peripheral blood tests at least 7 days apart; or platelet count slightly higher than 30 x 10\^9/L with dependence on platelet transfusion to maintain a safe platelet level. 5. Thrombocytopenia has persisted since the last chemotherapy treatment without a clear trend of spontaneous recovery. 6. Red blood cell count and neutrophil count are generally preserved, without clinically significant anemia or neutropenia. 7. Bone marrow assessment performed within 1 year after tumor diagnosis and chemotherapy shows no tumor cell infiltration; megakaryocyte count is normal or increased, with or without maturation impairment. 8. No hepatosplenomegaly, portal hypertension, or other evidence suggesting abnormal platelet redistribution as the main cause of thrombocytopenia. 9. Prior treatment with at least one thrombopoietin receptor agonist or recombinant human thrombopoietin for PICIT without response, defined as failure of platelet count to rise to a safe level or to at least 2 times baseline after at least 2 weeks of standard-dose treatment. 10. No prior use of Romiplostim N01. 11. Other platelet-raising medications have been discontinued before enrollment. No washout period is required for prior thrombopoietin receptor agonists; other investigational drugs or off-label treatments must be discontinued for at least 1 month before enrollment. 12. Ability to understand and sign the informed consent form and willingness to comply with study visits and procedures. 13. Participants of reproductive potential must agree to use effective contraception during study treatment. Female participants of childbearing potential must have a negative pregnancy test before enrollment.
Exclusion criteria
1. Other hematologic diseases that may affect hematopoiesis or cause thrombocytopenia, including but not limited to aplastic anemia, myelodysplastic syndrome, leukemia or other hematologic malignancies, or a clear history of primary immune thrombocytopenia. 2. Active recurrence or progression of the underlying tumor, or evidence of bone marrow metastasis or tumor cell infiltration on bone marrow examination. 3. Uncontrolled chronic viral infection, including hepatitis B, hepatitis C, or HIV infection, or active severe infection at screening or within 4 weeks before screening. 4. Severe cardiac, hepatic, renal, or other organ dysfunction, or any serious organic disease that would make the participant unable to tolerate study treatment. 5. Pregnancy or breastfeeding. 6. Known severe hypersensitivity to Romiplostim, Romiplostim N01, ATRA, or any component of the study drugs. 7. Prior Romiplostim treatment associated with severe adverse reactions or lack of efficacy. 8. Poor compliance, inability to complete treatment or follow-up, psychiatric or psychological condition that prevents understanding of the study procedures, or any other condition that, in the investigator's judgment, may increase study risk or interfere with interpretation of study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Platelet Response Rate at Week 12 | From randomization to 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Bleeding Events | From treatment start to Week 24 | Percentage of participants with any bleeding event and severity of bleeding events recorded during the study. |
| Incidence of Adverse Events and Serious Adverse Events | From first dose to Week 24 | Adverse events and serious adverse events will be recorded and graded according to CTCAE version 5.0 and summarized by treatment arm. |
| Incidence of Thromboembolic Events | From first dose to Week 24 | Percentage of participants with confirmed thromboembolic events during treatment and follow-up. |
| Time to Response | From treatment start to Week 24 | Time from treatment start to the first platelet count \>=30 x 10\^9/L. |
| Change in Platelet Count Over Time | Baseline; weekly during Weeks 1 to 12; every 2 weeks during Weeks 13 to 24 | Change in peripheral blood platelet count from baseline at scheduled study visits. |
| Sustained Platelet Response Rate During Weeks 13 to 24 | Weeks 13 through 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. |
| Complete Response Rate | Up to Week 24 | Percentage of participants with platelet count \>=100 x 10\^9/L and no bleeding for at least 2 consecutive weeks. |
| Partial Response Rate | Up to Week 24 | Percentage of participants with platelet count \>=30 x 10\^9/L and at least 2 times the baseline platelet count, with no bleeding. |
| Platelet Transfusion Requirement | From treatment start to Week 24 | Frequency and total amount of platelet transfusions during treatment and follow-up. |
| Duration of Response | From first documented response to Week 24 | Among responders, time from first achievement of platelet response to platelet count \<30 x 10\^9/L or the end of study follow-up. |
Countries
China
Contacts
CONTACTXiaohui Zhang, MD
CONTACTKexin Shen, MD
PRINCIPAL_INVESTIGATORXiaohui Zhang, MD
Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology
Outcome results
None listed