Clinical trial NCT04722952: PD-1 Inhibitor Combined With Azacytidine and Homoharringtonine，Cytarabine, G-CSF for Refractory or Relapsed AML
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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Immunotherapy
Refractory Leukemia
Relapsed Adult AML
Acute Myeloid Leukemia
Keywords: Acute Myeloid Leukemia
Refractory or Relapsed
Azacytidine
HAG regimen
PD-1 inhibitor
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2021-01-25
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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：

    1. ALT(SGPT) less than or equal to 2.5 × Upper Limit of Norma（ULN）；
    2. AST (SGOT) less than or equal to 2.5 × ULN；
    3. 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
    4. Serum Creatinine ≥ 30 mL/min
    5. 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

Primary outcomes:
measure: Complete remission， Incomplete blood count recovery，Partial remission（CR+CRi+PR）
timeFrame: 8 months
Secondary outcomes:
measure: Overall Response Rate （ORR）
timeFrame: 8 months
measure: Overall survival (OS)
timeFrame: 3 years
measure: Event free survival（EFS）
timeFrame: 3 years
measure: Progression free survival（PFS）
timeFrame: 3 years
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Han Yue, Ph.D
role: PRINCIPAL_INVESTIGATOR
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