PD-1 Inhibitor Combined With Azacytidine and Homoharringtonine，Cytarabine, G-CSF for Refractory or Relapsed AML

Study Overview
=================
Brief Summary
-----------------
This is an single center, single arm, phase 3 study to evaluate efficacy and safety of PD-1 Inhibitor combined with DNA methyltransferase inhibitor Azacytidine and HAG regimen for patients with relapsed and refractory acute myeloid leukemia.

Detailed Description
-----------------
Treatment for Acute Myeloid Leukemia（AML） that has not responded to treatment (refractory) or has returned after treatment (relapsed) often do not work. Researchers want to see if an immunotherapy drug, combined with a less intense chemotherapy, may be able to help.

Official Title
-----------------
an Single Center，Single Arm, Phase 3 Study to Evaluate Efficacy and Safety of PD-1 Inhibitor Combined With Azacytidine and HAG Regimen for Patients With Relapsed or Refractory Acute Myeloid Leukemia.

Conditions
-----------------
Immunotherapy, Refractory Leukemia, Relapsed Adult AML, Acute Myeloid Leukemia

Intervention / Treatment
-----------------
* Drug: Visilizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Chinese guidelines for the diagnosis and treatment of relapsed and refractory acute myeloid leukemia (2017 edition)，excludes acute promyelocytic leukemia (M3、APL) Hematopoietic stem cell transplantation ≥3 months, Discontinue immunosuppressant ≥3 weeks, Patients without graft-versus-host disease； Be at least 18 years of age on day of signing informed consent. Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group（ECOG） Performance Scale Demonstrate adequate organ function as defined below, all screening labs should be performed before treatment initiation： ALT(SGPT) less than or equal to 2.5 × Upper Limit of Norma（ULN）； AST (SGOT) less than or equal to 2.5 × ULN； Serum total bilirubin Less than or equal to 2.0 × ULN Note: If total bilirubin >2.0×ULN, subjects with Gilbert syndrome records are allowed to join the group Serum Creatinine ≥ 30 mL/min Total white blood cell (WBC) count ≤10,000/µL； Note: hydroxyurea therapy is allowed to reduce white blood cells to meet this inclusion criteria.white blood cells should be determined ≥24 hours after the last hydroxyurea administration. Final hydroxyurea administration should not ≤3 days prior to the first azacytidine administration. Treatment without anthracycline or demethylation. Ability to comprehend the investigational nature of the study and provide informed consent Exclusion Criteria: Patients with chronic myeloid leukemia，AML of other myeloproliferative disorders Malignant neoplasms with other progression Those who can not control severe infections and other underlying diseases can not tolerate chemotherapy Patients with cardiac insufficiency： ejection fraction (EF)<30%，New York Heart Association（NYHA） standards，Cardiac insufficiency II or above Patients with liver and kidney dysfunction：Serum bilirubin (SB)≥2mg/dl，AST is 2.5 times higher than normal upper limit, serum creatinine (SCr) is more than 2.5 mg/dl Serious mental illness uncooperative Refusal to join the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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: Anti-PD-1 mAb Combined With Azacytidine and HAG regimen<br>Anti-PD-1 mAb combined with DNA methyltransferase inhibitor Azacytidine and HAG regimen | Drug: Visilizumab<br>* Azacytidine 75mg/(m2.d) by IV on days 1-7 of every cycle. Anti-PD-1 mAb 200mg by IV on day 8 of every cycle. Homoharringtonine(HHT) 2mg/(m2.d) by IV on days 1-6 of every cycle Cytarabine 10mg/(m2.d) by SC on days 1-7 of every cycle Granulocyte colony-stimulating factor(G-CSF) 300ug/d by SC on days 1-7 of every cycle，until absolute neutrophil count(ANC) > 5X109／L or white blood cell（WBC）> 20X109／L.<br>* Other names: Cytarabine;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission， Incomplete blood count recovery，Partial remission（CR+CRi+PR） | Number of Participants (Responders) Achieving CR+CRi+PR After the Eighth Cycle Treatments | 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate （ORR） | Number of Participants (Responders) Achieving Overall Response Rate(ORR) After the Eighth Cycle Treatments | 8 months | 
| Overall survival (OS) | time from randomization to death from any cause | 3 years | 
| Event free survival（EFS） | The time between the beginning of the group and the occurrence of any event, including death, progression of the disease, chemotherapy regimen, conversion to chemotherapy, addition of other treatment, occurrence of fatal or intolerable side effects, etc | 3 years | 
| Progression free survival（PFS） | Time between the beginning of randomization and the progression (in any way) of tumorigenesis or (for any reason) death | 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acute Myeloid Leukemia, Refractory or Relapsed, Azacytidine, HAG regimen, PD-1 inhibitor