Sintilimab (One Anti-PD-1 Antibody) Plus Low-dose Bevacizumab for ctDNAlevel- Relapse and Clinical-relapse Oligodendroglioma

Inclusion Criteria:

1. Written informed consent and HIPAA authorization obtained from the subject/legalrepresentative prior to performing any protocol-related procedures, includingscreening evaluations
2. Subjects must be willing and able to comply with scheduled visits, treatment schedule,laboratory testing, and other requirements of the study, including disease assessmentby MRI and tumor in situ fluid (TISF) collection
3. Histologically confirmed diagnosis of oligodendroglioma(WHO III)
4. Resection surgery done at the study center (Henan Provincial People's Hospital), withan reservoir intraoperatively implanted connecting the surgical cavity and thesubscalp for postoperative noninvasive TISF collection
5. An interval of > 28 days and full recovery (i.e., no ongoing safety issues) fromsurgical resection prior to grouping
6. Karnofsky performance status (KPS) of 70 or higher
7. Life expectancy > 12 weeks

Exclusion Criteria:

1. More than two recurrences of oligodendroglioma
2. Presence of extracranial metastatic, significant leptomeningeal disease or tumorsprimarily localized to the brainstem or spinal cord
3. Any serious or uncontrolled medical disorder that, in the opinion of the investigator,may increase the risk associated with study participation or study drugadministration, impair the ability of the subject to receive protocol therapy, orinterfere with the interpretation of study results
4. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo,type I diabetes mellitus, residual hypothyroidism due to autoimmune condition onlyrequiring hormone replacement, psoriasis not requiring chronic and systemicimmunosuppressive treatment, or conditions not expected to recur in the absence of anexternal trigger are permitted to enroll. Subjects have any other condition requiringsystemic treatment with corticosteroids or other immunosuppressive agents within 14days. Inhaled or topical steroids and adrenal replacement doses >10mg daily prednisoneequivalent are permitted in absence of active autoimmune disease
5. Previous radiation therapy with anything other than standard radiation therapy (i.e.,focally directed radiation) administered as first line therapy
6. Previous treatment with carmustine wafer except when administered as first linetreatment and at least 6 months prior to randomization
7. Previous bevacizumab or other VEGF or anti-angiogenic treatment
8. Previous treatment with a PD-1, PD-L1 or CTLA-4 targeted therapy
9. Evidence of > Grade 1 CNS hemorrhage on the baseline MRI scan
10. Inadequately controlled hypertension (defined as systolic blood pressure ≥160 mmHg and /or diastolic blood pressure ≥100 mmHg) within 7 days of first study treatment
11. Prior history of hypertensive crisis, hypertensive encephalopathy, reversibleposterior leukoencephalopathy syndrome (RPLS)
12. Prior history of gastrointestinal diverticulitis, perforation, or abscess
13. Clinically significant (i.e., active) cardiovascular disease, for examplecerebrovascular accidents ≤ 6 months prior to study enrollment, myocardial infarction ≤ 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF), or serious cardiacarrhythmia uncontrolled by medication or potentially interfering with protocoltreatment
14. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair orrecent arterial thrombosis) within 6 months prior to start of study treatment. Anyprevious venous thromboembolism ≥ NCI CTCAE Grade 3 within 3 months prior to start ofstudy treatment
15. History of pulmonary hemorrhage/hemoptysis ≥ grade 2 (defined as ≥ 2.5 mL bright redblood per episode) within 1 month prior to randomization
16. History or evidence of inherited bleeding diathesis or significant coagulopathy atrisk of bleeding (i.e., in the absence of therapeutic anticoagulation)
17. Current or recent (within 10 days of study enrollment) use of anticoagulants that, inthe opinion of the investigator, would place the subject at significant risk forbleeding. Prophylactic use of anticoagulants is allowed
18. Surgical procedure (including open biopsy, surgical resection, wound revision, or anyother major surgery involving entry into a body cavity) or significant traumaticinjury within 28 days prior to first study treatment, or anticipation of need formajor surgical procedure during the course of the study
19. Minor surgical procedure (e.g., stereotactic biopsy within 7 days of first studytreatment; placement of a vascular access device within 2 days of first studytreatment)
20. History of intracranial abscess within 6 months prior to randomization
21. History of active gastrointestinal bleeding within 6 months prior to randomization
22. Serious, non-healing wound, active ulcer, or untreated bone fracture
23. Subjects unable (due to existent medical condition, e.g., pacemaker or ICD device) orunwilling to have a head contrast enhanced MRI
24. Positive test for hepatitis B virus surface antigen (HBV sAg) or detectable hepatitisC virus ribonucleic acid (HCV RNA) indicating acute or chronic infection
25. Known history of testing positive for human immunodeficiency virus (HIV) or knownacquired immunodeficiency syndrome (AIDS)
26. History of severe hypersensitivity reaction to any monoclonal antibody
27. Patients that require decadron > 4 mg/ day or equivalent of steroids