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

Sponsor

The First Affiliated Hospital of Soochow University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04722952

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Immunotherapy Refractory Leukemia Relapsed Adult AML Acute Myeloid Leukemia	Drug: Visilizumab	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

Actual Study Start Date :

May 1, 2021

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jan 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Anti-PD-1 mAb Combined With Azacytidine and HAG regimen Anti-PD-1 mAb combined with DNA methyltransferase inhibitor Azacytidine and HAG regimen	Drug: Visilizumab 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. Other Names: Azacytidine Homoharringtonine Cytarabine

Arm

Intervention/Treatment

Experimental: Anti-PD-1 mAb Combined With Azacytidine and HAG regimen

Anti-PD-1 mAb combined with DNA methyltransferase inhibitor Azacytidine and HAG regimen

Drug: Visilizumab

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.

Other Names:

Azacytidine

Homoharringtonine

Cytarabine

Outcome Measures

Primary Outcome Measures

Complete remission， Incomplete blood count recovery，Partial remission（CR+CRi+PR） [8 months]
Number of Participants (Responders) Achieving CR+CRi+PR After the Eighth Cycle Treatments

Secondary Outcome Measures

Overall Response Rate （ORR） [8 months]
Number of Participants (Responders) Achieving Overall Response Rate(ORR) After the Eighth Cycle Treatments
Overall survival (OS) [3 years]
time from randomization to death from any cause
Event free survival（EFS） [3 years]
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
Progression free survival（PFS） [3 years]
Time between the beginning of randomization and the progression (in any way) of tumorigenesis or (for any reason) death

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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