Application of PD-1 Inhibitors, Tenofovir, Chidamide, and Lenalidomide in Relapsed/Refractory EBV-associated Lymphoproliferative Disorders.

Launched by THE AFFILIATED HOSPITAL OF XUZHOU MEDICAL UNIVERSITY · Aug 14, 2025

Keywords

ClinConnect Summary

This clinical trial is exploring a new combination treatment for people with a rare and challenging condition called EBV-associated lymphoproliferative disorders (LPDs). These disorders involve abnormal growth of certain immune cells linked to the Epstein-Barr virus (EBV). The study will test how safe and effective a mix of four medicines—including a PD-1 inhibitor (which helps the immune system fight cancer), tenofovir (which can reduce the virus), chidamide, and lenalidomide—is for patients whose disease has come back or hasn’t responded to previous treatments. The main goal is to see how many patients show improvement after three months, and the study will also look at how long patients live, how long their disease stays under control, and any side effects.

People who might join this trial are those diagnosed with EBV-related LPDs confirmed by specific tests, are 75 years old or younger, and have measurable disease that doctors can monitor during the study. Participants should be reasonably healthy with a good performance status and expect to live at least three months. They also need to be willing and able to follow the study’s schedule. The trial is not yet open for recruiting, but once it starts, participants can expect close monitoring to track how well the treatment works and to watch for any side effects. This study aims to offer a new hope by targeting the virus and boosting the body’s immune response against this difficult-to-treat disease.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Histologically confirmed EBV-associated lymphoproliferative disorders, including EBV-positive B-cell LPD and EBV-positive T/NK-cell LPD, with EBV-encoded RNA (EBER)+ by in situ hybridization, or EBV nuclear antigen (EBNA)+, or latent membrane protein (LMP1/2)+ in the lesion tissue.
• • 2. Age ≤75 years with an ECOG performance status ≤2.
• • 3. At least one bidimensionally measurable lesion for evaluation: for nodal lesions, longest diameter ≥1.5 cm and shortest diameter ≥1.0 cm; for extranodal lesions, longest diameter ≥1.0 cm; or ≥20% monoclonal EBV-infected lymphocytes detected by flow cytometry.
• • 4. Expected survival of more than 3 months.
• • 5. Ability to comply with follow-up. Patients must be aware of the nature of their disease and voluntarily agree to participate in the study and follow-up.
• Exclusion Criteria:
• • 1. Patients with impaired liver or kidney function, defined as serum direct bilirubin, indirect bilirubin, and/or ALT, AST, or serum creatinine levels \>2 times the upper limit of normal, unless deemed lymphoma-related.
• • 2. Patients with bone marrow failure, defined as absolute neutrophil count (ANC) \<1.5×10⁹/L or platelets \<75×10⁹/L, unless the hematologic abnormalities are considered due to bone marrow infiltration by lymphoma.
• • 3. Patients who have experienced grade ≥3 neurotoxicity within the past 2 weeks.
• • 4. Patients with chronic heart failure classified as NYHA Class III or IV, or with left ventricular ejection fraction \<50%, or with a history within the past 6 months of any of the following: acute coronary syndrome, acute heart failure (Class III or IV), or significant ventricular arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation, or post-resuscitation sudden cardiac arrest).
• • 5. Patients with AIDS, syphilis, or active hepatitis B (HBV DNA \>1×10⁴ copies/ml) or active hepatitis C infection.
• 6. Patients diagnosed with malignancies other than lymphoma or currently undergoing treatment for other cancers, except:
• • ① Those who have received curative treatment and have been disease-free for ≥5 years prior to enrollment;
• • ② Patients with adequately treated, non-melanoma skin cancers such as basal cell carcinoma without evidence of disease;
• • ③ Patients with adequately treated carcinoma in situ of the cervix without evidence of disease.
• • 7. Patients with other hematologic diseases (e.g., hemophilia, myelofibrosis) considered unsuitable for the study by the investigator.
• • 8. Patients with severe active infections.
• • 9. Patients who underwent Grade 2 or higher surgery within 3 weeks before treatment initiation.
• • 10. Patients with a history of substance abuse, or medical, psychological, or social conditions that may interfere with study participation or evaluation, as judged by the investigator.
• • 11. Any other condition the investigator considers unsuitable for study enrollment.
• • 12. Known hypersensitivity to any component of the investigational drugs.