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

Phase 3

• Conditions: Immunotherapy; Refractory Leukemia; Acute Myeloid Leukemia; Relapsed Adult AML
• Interventions: Drug: Visilizumab

• Registration Number: NCT04722952
• Lead Sponsor: The First Affiliated Hospital of Soochow University

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.

Study Timeline

• Study First Submitted: 2020-12-21
• Study First Submitted QC: 2021-01-21
• Study First Posted: 2021-01-25
• Study Start: 2021-05-01
• Status Verified: 2021-12
• Last Update Submitted: 2021-12-02
• Last Update Posted: 2021-12-03
• Primary Completion: 2023-01-01
• Study Completion: 2024-01-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Anti-PD-1 mAb Combined With Azacytidine and HAG regimen	Visilizumab	Anti-PD-1 mAb combined with DNA methyltransferase inhibitor Azacytidine and HAG regimen

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Overall Response Rate （ORR）	8 months	Number of Participants (Responders) Achieving Overall Response Rate(ORR) After the Eighth Cycle Treatments
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
Overall survival (OS)	3 years	time from randomization to death from any cause

Trial Locations

Locations (1)

The First Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China