Combined PD1 Inhibitor and Decitabine in Elderly Patients With Relapse and Refractory Acute Myeloid Leukemia

Phase 2

• Conditions: Acute Myeloid Leukemia
• Interventions: Drug: Camrelizumab(SHR-1210); Drug: Decitabine

• Registration Number: NCT04353479
• Lead Sponsor: Shanghai Jiao Tong University School of Medicine

Brief Summary

This is an open-label, single arm, phase 2 study to evaluate efficacy and safety of PD1 inhibitor Camrelizumab(SHR-1210) combined with DNA methyltransferase inhibitor decitabine in elderly patients with relapse and refractory acute myeloid leukemia.

Detailed Description

In this single-center, open-label, nonrandomized, no control, prospective clinical trial, 29 relapsed or refractory acute myeloid leukemia patients will be enrolled. Patients will be administered Camrelizumab(SHR-1210) at D1 and D15 and decitabine at D1-5. Treatment repeats every 28 days until disease progression or unacceptable toxicity.

Study Timeline

• Status Verified: 2020-04
• Study First Submitted: 2020-04-14
• Study First Submitted QC: 2020-04-16
• Last Update Submitted: 2020-04-16
• Study First Posted: 2020-04-20
• Last Update Posted: 2020-04-20
• Study Start: 2020-04-25
• Primary Completion: 2020-12-31
• Study Completion: 2022-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

• Age: 60-75

• Relapsed and refractory patients with acute myeloid leukemia via morphology and immunology

• ECOG：0-2

• Life expectancy ≥ 3 months

• Adequate laboratory parameters during the screening period as evidenced by the following:

  1. Creatinine clearance≥30 mL/min and serum Creatinine ≤ 160µmol/L
  2. ALT and AST ≤ 3 × upper limit of normal (ULN)
  3. FEV1,FVC,DLCO ≥ 50% predicted value
  4. Left ventricular ejection fraction (LVEF) ≥ 40%, no symptomatic arrhythmia
  5. Able to understand and sign an informed consent form (ICF).

Exclusion Criteria

• Treatment-related AML
• Allergic to Camrelizumab, Decitabine, other monoclonal antibody or pharmaceutical excipients
• Use of immunosuppressive drug within 2 weeks before entering the group
• Abnormal liver and kidney function(does not meet the inclusion criteria)
• Suffering from heart failure
• Active tuberculosis or HIV positive
• Active hepatitis: Hepatitis B(HBsAg positive and HBV DNA≥500IU/mL), and hepatitis C(HCV RNA positive, abnormal liver function) ,Hepatitis B and hepatitis C infection in common.
• Active, known or suspected autoimmune disease. Subjects who were in a stable state without systemic immunosuppressive therapy were admitted
• Concurrent medical condition requiring the long-term use of immunosuppressive medications, or immunosuppressive doses of systemic corticosteroids > 10 mg/day topical prednisone or equivalent
• Suffer from other hematological neoplasm
• Known history of use other immune checkpoint inhibitor
• Other factors that may lead to the study termination, such as severe disease or abnormal laboratory tests or family or social factors affecting subjects safety or test data and sample collection.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Camrelizumab(SHR-1210) Combined With Decitabine	Camrelizumab(SHR-1210)	Patients will be administered Camrelizumab(SHR-1210) at D1 and D15 and decitabine at D1-5. Treatment repeats every 28 days until disease progression or unacceptable toxicity.
Camrelizumab(SHR-1210) Combined With Decitabine	Decitabine	Patients will be administered Camrelizumab(SHR-1210) at D1 and D15 and decitabine at D1-5. Treatment repeats every 28 days until disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Overall response rate	6 months	CR, CRi, and morphologic leukemia-free state (MLFS)
Complete remission (CR) rate	6 months	Blast and promyelocytic leukemia less than 5% in bone marrow

Secondary Outcome Measures

Name	Time	Method
12-month overall survival rate	12 months	To evaluate overall survival rate at 12 months from study entry.
Progress-free survival (PFS)	2 years	PFS is defined from the date of entry on study until disease progression, including treatment failure, relapse from CR, or death from any causes.
Overall survival (OS)	2 years	OS is defined for patients entering the study as time to death of all causes.
6-month overall survival rate	6 months	To evaluate overall survival rate at 6 months from study entry.
Hematological and non-hematological toxicity	2 years	Assessed according to the Common Terminology Criteria for Adverse Events Version 4.03.