PD-1 Antibody Improve Mixed Chimerism (HLH)

PD-1 Antibody Improve Mixed Chimerism in Patients With Hemophagocytic Lymphohistiocytosis After Allo-HCT

PD-1/PD-L1 pathway play an important role in Inhibiting the function of antigen-specific CD8+T cells, thus matter a lot in immune escape. We intend to use PD-1 antibody to improve the function of lymhocyte and improve the chimerism in patients after allo-HCT.

Study Overview

• Status: Not yet recruiting
• Conditions: PD-1 Antibody; Mixed Chimerism
• Intervention / Treatment: Drug: Toripalimab Injection

Detailed Description

Mixed chimerism is a trouble condition after allogeneic hematopoietic cell transplantation (Allo-HCT),all targeted treatment are aimed to improve the function of lymphocyte recipient. PD-1 antibody was reported to restored the function of impaired lymphocyte. Therefore, we want to use PD-1 antibody to improve the function of lymhocyte and improve the chimerism in HLH patients after allo-HCT.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yahong You; Phone Number: 17810283962; Email: 15332022659@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. EBV-HLH according to the HLH-04 diagnostic criteria.
2. After allo-HCT, have achieved engraftment and reconstitute of hematopoiesis. have achieved full donor chimerism.
3. Withdraw immunosuppressive agent, chimeric rate was 80%-95%
4. Age >18 years old, gender is not limited.
5. no graft-versus-host disease was observed.
6. No secondary graft failure (ANC <0.5*10^9/l,PLT <10*10^9/l)
7. Before the start of the study, aminopherase (ALT/AST) and total bilirubin were normal. Serum creatinine ≤ 1.5 times the upper limit of Normal (ULN); No thyroid dysfunction. The left ventricular ejection fraction (LVEF) was normal.
8. Informed consent.

Exclusion Criteria:

1. Allergic to the test drug ingredients or to a more severe allergic constitution.
2. Chimeric rate continue to decline after 2 weeks of toripalimab Injection used.
3. Serious immunoreaction: myocardial damage, hepatitis, pneumonia.
4. Central nervous system symptoms.
5. Serious mental illness.
6. Active bleeding of the internal organs
7. Uncontrollable infection；
8. Pancreatitis history. Patients unable to comply during the trial and/or follow-up phase;
9. Participate in other clinical research at the same time.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PD-1 antibody for mixed chimerism; PD-1 antibody (Toripalimab Injection) used for mixed chimerism in HLH patients after allo-HCT	Drug: Toripalimab Injection; Toripalimab Injection used for mixed chimerism between 80%-95% in HLH patients. Dose: 240mg toripalimab Injection, two weeks later, the same dose will be repeated if patients have some improve in the chimeric rate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chimeric rate	Chimeric rate in bone marrow or peripheral blood of HLH patients	4 weeks after toripalimab injection was used

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
treatment-related adverse events as assessed by CTCAE v5.0；	Adverse events including thyroid function，liver function damage, myelosuppression, infection, bleeding and so on.	every 2 weeks after intervention, until 8 weeks after the use of PD-1 antibody

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	From enrollment until death or the end of the experiment	1 year

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2021
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: December 27, 2020
• First Submitted That Met QC Criteria: June 27, 2021
• First Posted (Actual): June 29, 2021

Study Record Updates

• Last Update Posted (Actual): June 29, 2021
• Last Update Submitted That Met QC Criteria: June 27, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: PD-1; Chimerism
• Other Study ID Numbers: PD-1, mixed chimerism

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