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

Sponsor

Shanghai Jiao Tong University School of Medicine (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04353479

Collaborator

(none)

Enrollment

Arm

32.2

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Camrelizumab(SHR-1210) Drug: Decitabine	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

29 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Combined PD1 Inhibitor and Decitabine in Elderly Patients With Relapse and Refractory Acute Myeloid Leukemia : An Open-Label, Single-Arm, Phase 2 Study.

Anticipated Study Start Date :

Apr 25, 2020

Anticipated Primary Completion Date :

Dec 31, 2020

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Camrelizumab(SHR-1210) Combined With 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.	Drug: Camrelizumab(SHR-1210) A humanized monoclonal immunoglobulin Other Names: PD1 inhibitor Drug: Decitabine A DNA methyltransferase inhibitor Other Names: 5-aza-2- deoxycytidine

Arm

Intervention/Treatment

Experimental: Camrelizumab(SHR-1210) Combined With 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.

Drug: Camrelizumab(SHR-1210)

A humanized monoclonal immunoglobulin

Other Names:

PD1 inhibitor

Drug: Decitabine

A DNA methyltransferase inhibitor

Other Names:

5-aza-2- deoxycytidine

Outcome Measures

Primary Outcome Measures

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

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.
12-month overall survival rate [12 months]
To evaluate overall survival rate at 12 months from study entry.
Hematological and non-hematological toxicity [2 years]
Assessed according to the Common Terminology Criteria for Adverse Events Version 4.03.

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Creatinine clearance≥30 mL/min and serum Creatinine ≤ 160µmol/L
ALT and AST ≤ 3 × upper limit of normal (ULN)
FEV1,FVC,DLCO ≥ 50% predicted value
Left ventricular ejection fraction (LVEF) ≥ 40%, no symptomatic arrhythmia
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.