Programmed Cell Death Protein-1 (PD-1) Monoclonal Antibody for EBV-HLH and CAEBV as First-line Therapy (SEHC)

A Clinical Trial of PD-1 Monoclonal Antibody as First-line Induction Therapy for EBV-associated Hemophagocytic Syndrome (EBV-HLH) or Chronic Active EBV Infection (CAEBV)

EBV-HLH and CAEBV are both caused by EBV infection, part of them can rapidly lead to a syndrome of severe, life-threatening hyper-inflammation, with poor prognosis. Currently, the most effective treatment remains unknown. This study is trying to evaluate the efficacy and safety of PD-1 monoclonal antibody as a first-line therapy for EBV-HLH and CAEBV.

Study Overview

• Status: Recruiting
• Conditions: EBV Infection
• Intervention / Treatment: Drug: PD-1 monoclonal antibody

Detailed Description

Eligible patients who were diagnosed with EBV-HLH or CAEBV, age between 12 and 70 years, were enrolled in this study. All of them need to sign the informed consent first.

PD-1 monoclonal antibody 200mg is infused intravenously once for patients whose age >=18 years, or age <18 years but weight >=40kg. While for patients age <18 years, the dose of PD-1 monoclonal antibody is 3mg/kg. Besides, optimal supportive care is necessary.

Ruxolitinib and/or low-dose glucocorticoid can be used to reduce inflammation.

Cerebrospinal fluid parameters are examined, and methotrexate 15mg combined with dexamethasone will be intrathecal injected without contraindications.

Clinical and laboratory indicators are investigated weekly to evaluate the efficacy and toxicity.

If patients achieve partial response/complete response within 14 days after PD-1 monoclonal antibody, the clinical observations are stopped. If not, the observation period is prolonged to 21 days.

If disease progress at day 21, this study is terminated, and the patient should be transfer to other treatments as soon as quickly.

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Xuefeng He, doctor; Phone Number: 86-18914031640; Email: hexuefeng@suda.edu.cn
• Study Contact Backup: Name: Xiaoli Li, doctor; Phone Number: 86-13625270981; Email: 397640784@qq.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: Xuefeng He, doctor; Phone Number: 86-18914031640; Email: hexuefeng@suda.edu.cn
      • Contact: Xiaoli Li, doctor; Phone Number: 86-13625270981; Email: 397640784@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 70 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Meet the diagnostic criteria of EBV-HLH or CAEBV.
2. Newly diagnosed patients.
3. Eastern Cooperative Oncology Group score 0-3.
4. Total bilirubin <= 10 times of upper limit of normal (except for those caused by EBV-HLH or CAEBV), and serum creatinine <= 1.5 times of upper limit of normal.
5. Serum HIV antigen or antibody is negative.
6. Hepatitis C virus (HCV) antibody is negative, or HCV antibody is positive, but HCV-RNA is negative.
7. Both HbsAg and HbcAb for Hepatitis B virus (HBV) are negative. If not, the quantification of HBV-DNA needs to be <1*10e3 IU/ml.
8. The patient or his/her guardian must be able to understand and be willing to participate in this study, and sign the informed consent.

Exclusion Criteria:

1. Non EBV-HLH or CAEBV patients.
2. Refractory or relapsed EBV-HLH or CAEBV.
3. Heart function above grade II (NYHA).
4. Patients suffered from other uncontrollable active infections.
5. Pregnant or lactating women.
6. Patients with mental disorders and cannot cooperate with the requirements of research, treatment and monitoring.
7. Active visceral bleeding.
8. Allergic to PD-1 monoclonal antibody.
9. Patients with known autoimmune diseases.
10. Participate in other clinical research at the same time.
11. The investigator judges that the patient has other reasons not suitable for this study, or participating in the study will bring great risks to the patient.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PD-1 monoclonal antibody group; PD-1 monoclonal antibody 200mg is infused intravenously once for patients whose age >=18 years, or age <18 years but weight >=40kg. While for patients age <18 years, the dose of PD-1 monoclonal antibody is 3mg/kg.	Drug: PD-1 monoclonal antibody; PD-1 monoclonal antibody is a new attempt treatment, and ruxolitinib and/or low-dose dexamethasone can reduce the inflammation that occur in EBV-HLH or CAEBV.; Other Names: dexamethasone; ruxolitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	complete response and/or partial response rate	3 weeks
EBV-DNA viral load	EBV-DNA copy by polymerase chain reaction	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time for treatment works	Time to achieve partial response or complete response	3 weeks
Toxicity of PD-1 monoclonal antibody	Side effects related to immunotherapy	3 weeks

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Investigators: Principal Investigator: Xuefeng He, doctor, The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 15, 2021
• Primary Completion (ANTICIPATED): April 30, 2023
• Study Completion (ANTICIPATED): April 30, 2023

Study Registration Dates

• First Submitted: September 1, 2021
• First Submitted That Met QC Criteria: September 1, 2021
• First Posted (ACTUAL): September 9, 2021

Study Record Updates

• Last Update Posted (ACTUAL): September 9, 2021
• Last Update Submitted That Met QC Criteria: September 1, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; DNA Virus Infections; Tumor Virus Infections; Herpesviridae Infections; Infections; Epstein-Barr Virus Infections; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: EBV and CAEBV 001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No