Clinical trial NCT04944511: PD-1 Antibody Improve Mixed Chimerism
Official title: PD-1 Antibody Improve Mixed Chimerism in Patients With Hemophagocytic Lymphohistiocytosis After Allo-HCT
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: PD-1 Antibody
Mixed Chimerism
Keywords: Chimerism
PD-1
Lead sponsor: Beijing Friendship Hospital
Sponsor class: OTHER
First posted: 2021-06-29
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: one group of HLH patients with mixed chimerism (80%-95%), PD-1 antibody will be used to improve the chimerism
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Chimeric rate
timeFrame: 4 weeks after toripalimab injection was used
Secondary outcomes:
measure: treatment-related adverse events as assessed by CTCAE v5.0；
timeFrame: every 2 weeks after intervention, until 8 weeks after the use of PD-1 antibody
Other outcomes:
measure: Survival
timeFrame: 1 year
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
Study officials:
affiliation: Beijing Friendship Hospital
name: Zhao Wang
role: PRINCIPAL_INVESTIGATOR
References: