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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Camrelizumab(SHR-1210); Drug: Decitabine

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 Type: Interventional
• Enrollment (Anticipated): 29
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kai Xue; Phone Number: +86-13818659448; Email: xuekaishanghai@126.com
• Study Contact Backup: Name: Hongming Zhu; Email: daphnezhming@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: Junmin Li, Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): April 25, 2020
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: April 14, 2020
• First Submitted That Met QC Criteria: April 16, 2020
• First Posted (Actual): April 20, 2020

Study Record Updates

• Last Update Posted (Actual): April 20, 2020
• Last Update Submitted That Met QC Criteria: April 16, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; PD1 inhibitor; DNA methyltransferase inhibitor
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine; Immune Checkpoint Inhibitors
• Other Study ID Numbers: MA-AML-II-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No