Prospective Study of Immune Function and PD-1 Antibody Therapy Efficacy Predictors on CAEBV and EBV-HLH Patients

NCT05841342 | Unknown

• 1 other identifier: BFH20221009004
• Study Type: observational
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective case-control study aims to evaluate the immune function and find PD-1 antibody efficacy predictors on Chronic Active Epstein-Barr Virus Infection and Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis by detecting lymphocyte subsets proportions in peripheral blood mononuclear cells and the positive proportion of PD-1, PD-L1 and other indicators in each lymphocyte subsets in healthy people and patients using flow cytometry before and after the initial PD-1 therapy.

Conditions

Secondary Hemophagocytic Lymphohistiocytosis; Chronic Active Epstein-Barr Virus Infection

Outcome Measures

Primary Outcomes (1)

• EBV-DNA

  Treatment effectiveness is defined: EBV-DNA copies/ml in peripheral blood turns negative, and the involved tissues (such as lymph nodes, bone marrow, skin, etc.) are negative in EBER test or the EBV copy number has decreased by more than 2 orders of magnitude, but it is still positive.

  Change from before and 2 weeks after initiating PD-1 blockade therapy.

Secondary Outcomes (3)

• CAEBV Evaluation of treatment response

  Change from before and 2 weeks after initiating PD-1 blockade therapy.

• EBV-HLH Evaluation of treatment response

  Change from before and 2 weeks after initiating PD-1 blockade therapy.

• Progression Free Survival

  6 months

Study Arms (2)

Healthy Control

Healthy male or female aged 2-80 years with negative EBV-DNA quantitative test results within the last week.

Other: No intervention

CAEBV or EBV-HLH Patients

Patients aged 2-80 years who fulfilled the diagnostic criteria for CAEBV or EBV-HLH. The diagnostic criteria for CAEBV as defined in the recently revised World Health Organization classification include persistent IM-like symptoms for more than three months, increased EBV DNA (\>10\^2.5 copies/mg) in peripheral blood, histological evidence of organ disease, and EBV RNA or viral protein in affected tissues. Patients diagnosed with EBV-HLH must meet five of the following eight HLH-2004 diagnostic criteria: 1. temperature 38.5 ℃ and above; 2. splenomegaly; 3. two or three lines of hemocytopenia, i.e. hemoglobin (HB) \<90 g/L, platelets (PLT) \<100 × 10\^9/L or neutrophils (N) \<1 × 10\^9/L; 4. triacylglycerol (TG) ≥ 3 mmol/ L or fibrinogen (Fbg) \<1.5 g/L; 5. serum ferritin (SF) ≥ 500 mg/L; 6. phagocytosis found in bone marrow, spleen, liver or lymph nodes; 7. soluble CD25 (sCD25) ≥ 2400 U/mL; 8. low or absent natural killer (NK) cell activity.

Other: No intervention

Interventions

No intervention OTHER

No intervention

CAEBV or EBV-HLH Patients; Healthy Control

Eligibility Criteria

• Age: 2 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy people and patients with CAEBV or secondary EBV-HLH.

You may qualify if:

• Before the start of the study, total bilirubin ≤10 times the upper limit of normal, serum creatinine ≤1.5 times the normal value; fibrinogen can be corrected to ≥0.6g/L after infusion.
• Serum HIV antigen or antibody negative.
• HCV antibody negative, or HCV antibody positive, but HCV RNA negative.
• HBV surface antigen and HBV core antibody are both negative. If any of the above is positive, peripheral blood hepatitis B virus DNA titer detection is required, and the number of copies less than 1×103 copies/ml can be included in the group.
• LVEF ≥ 50% by cardiac echocardiography.
• Women of childbearing age must be confirmed by a pregnancy test that they are not pregnant, and are willing to take effective contraceptive measures during the test period and within ≥ 12 months after the last dose. Women during pregnancy and lactation cannot participate. Contraceptive measures should be taken during the test period and within ≥3 months after the last dose.
• Informed consent obtained.

You may not qualify if:

• According to the New York Heart Association (NYHA) score, patients with heart disease of grade II or above (including grade II);
• Pregnant or lactating women and patients of childbearing age who refused to take appropriate contraceptive measures during this trial.
• Those who are allergic to rituximab ingredients or have more severe allergic constitution;
• Severe hypogammaglobulinemia.
• Active massive hemorrhage of internal organs (including gastrointestinal hemorrhage, alveolar hemorrhage, intracranial hemorrhage, etc.);
• Uncontrolled active infection (including lung infection, intestinal infection, etc.);
• HBV surface antigen and/or HBV core antibody are positive, and the peripheral blood hepatitis B virus DNA test confirms the existence of active hepatitis B patients.
• Severe mental illness;
• Patients who were not compliant during the trial and/or follow-up period.
• Concurrently participate in other clinical investigators.

Sponsors & Collaborators

• Beijing Friendship Hospital: lead

Study Sites (1)

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, 100050, China

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

10ml venous blood was extracted and peripheral blood mononuclear cells were extracted for flow cytometry detection. The detection contents included the frequencies of lymphocyte subsets, the positive proportion of PD-1/PD-L1 and EBER positive proportion in each subgroup.

Central Study Contacts

Zhao Wang

CONTACT

86-010-63139862; zhaowww263@yahoo.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: April 22, 2023
• First Posted: May 3, 2023
• Study Start: October 1, 2022
• Primary Completion: April 30, 2024
• Study Completion: June 30, 2024
• Last Updated: May 3, 2023

Record last verified: 2023-04

Locations

CN (1)