PD-1 Inhibitor, Azacitidine and Low-dose DLI in AML Relapse After Allo-HSCT

Study Overview
=================
Brief Summary
-----------------
This study aims to evaluate the efficacy and safety of PD-1 inhibitor, Azacitidine, and low-dose DLI in AML relapse After allogeneic hematopoietic stem cell transplantation

Official Title
-----------------
Efficacy and Safety of PD-1 Inhibitor, Azacitidine and Low-dose DLI in AML Relapse After Allogeneic Hematopoietic Stem Cell Transplantation

Conditions
-----------------
Acute Myeloid Leukemia

Intervention / Treatment
-----------------
* Drug: Azacitidine
* Biological: Donor lymphocyte infusion
* Drug: Camrelizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with a diagnosis of AML relapse after allogeneic hematopoietic stem cell transplantation. Adequate organ function. Be able to understand and sign informed consent. Age 18 to 60 years old. Serum pregnancy test for females of childbearing potential that is negative within one week prior to initiation of first dose of treatment. Female patients of childbearing potential and sexually active males must agree to use a highly effective method of contraception throughout the study and for at least 90 days after the last dose of assigned treatment. ECOG performance status ≤ 1. Known HLA-matched donor without contraindications to donate. Life expectancy > 3 months. Exclusion Criteria: Diagnosis of anther malignant disease. Suspected or proven acute or chronic GVHD. Proven central nervous system leukemia. Prior treatment with anti-PD-1, anti-PD-L1, or DLI. HLA loss positive. Known active viral infection with known human immunodeficiency virus (HIV) or viral hepatitis type B (HBV) or C (HCV) or Corona Virus Disease 2019(COVID-19); Uncontrolled systemic fungal, bacterial, or viral infection. Known or suspected hypersensitivity to PD-1 inhibitor or azacytidine. Participation in another clinical study within 3 months. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of study procedures.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Camrelizumab, Azacitidine and low-dose Donor lymphocyte infusion<br>Patients are given azacytidine for 7 days, followed by 4 DLI treatments on Days 10, 17, 24 and 31, with the dose of DLI and Camrelizumab adjusted according to the donor source. Camrelizumab infusions were given 3 hours after completion of the 1st and 3rd DLIs, respectively. | Drug: Azacitidine<br>* Azacitidine 75 mg/m2 subcutaneously once daily on days 1-7.<br>Biological: Donor lymphocyte infusion<br>* The 4 DLI doses (dose range: ±10%) of sib-matched donor HSCT patients were 1×10^6/kg, 5×10^6/kg, 1×10^7/kg, 5×10^7/kg; The 4 DLI doses (dose range: ±10%) of haploidentical or unrelated donor HSCT patients were 1×10^5/kg, 5×10^5/kg, 1×10^6/kg, 5×10^6/kg.<br>Drug: Camrelizumab<br>* Camrelizumab 200mg Q2W for sib-matched donor HSCT patients, 100mg Q2W for haploidentical or unrelated donor HSCT patients.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | The overall response (completed remission, completed remission with incomplete blood count recovery) | ORR assessment is at day 39 (±2). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is measured from the time of enrollment to this trial to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive. | 2 years | 
| Progression-Free Survival (PFS) | PFS is measured from the time of enrollment to this study to progression or death. | 2 years | 
| Adverse events | It is evaluated and graded according to CTCAE 5.0. | 1 month | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PD-1 inhibitor, Azacitidine, low-dose DLI