Prevention and Treatment of Differentiation Syndrome in Patients With Acute Promyelocytic Leukemia

Phase 4

• Conditions: Safety and Efficacy

• Registration Number: NCT04446806
• Lead Sponsor: The First Affiliated Hospital of Soochow University

Brief Summary

With the introduction of all-trans-retinoic acid (ATRA) and arsenic,the outcome of patients with acute promyelocytic leukemia (APL)has been improved considerably over the last decades.However，early deaths (EDs), mainly due to APL-specific coagulopathy, differentiation syndrome (DS)emerge as a major threat to APL patients.We observe and evaluate the effectivity of induction therapy in patients with APL. Administrate intravenous dexamethasone to prevent or preemptive treat DS. Assess the efficacy and safety of ruxolitinib as second treatment in patients with severe DS with no respond to dexamethasone.Furthermore，the changes of spectrum of cytokines are monitered to find the relationship between the cytokines and the severity of DS.

Detailed Description

Adults ages 18-75 with primary acute promyelocytic leukemia.

Design:

The induction therapy with ATRA 25mg/m2/d and ATO 10mg/kg/d should be started as soon as the diagnosis of APL confirmed.

Intravenous dexamethasone at a dose of 5-20 mg daily must be started if the WBC count greater than 5e+9/L (before or during the treatment with ATRA) as prevention or preemptive therapy of DS.

Idarubicin (4-10 mg/m2 /d\*3d) and hydroxyurea（1.0-3.0g/d）can be given as leukocyte lowering therapy which may lessen the risk of DS.

When the progression of clinical symptoms of DS with no response to dexamethasone,ATRA must be stopped and ruxolitinib (5-20mg /d) should be administrated to reduce the production of cytokines.

Participants should stay in the hospital during the treatment for about 4 weeks.

The changes of spectrum of cytokines are monitored to discover the potential relationship between the cytokines and the severity of DS.

Participants will visit every 1 months after CR for 3 years.

Study Timeline

• Study Start: 2019-06-01
• Status Verified: 2020-03
• Study First Submitted: 2020-03-29
• Study First Submitted QC: 2020-06-22
• Last Update Submitted: 2020-06-22
• Study First Posted: 2020-06-25
• Last Update Posted: 2020-06-25
• Primary Completion: 2020-12-31
• Study Completion: 2021-05-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Clinical diagnosis of primary acute promyelocytic leukemia.
• ECOG score≤3.
• Must be able to understand and willing to participate in the study and sign the informed consent.

Exclusion Criteria

• Refractory/secondary acute promyelocytic leukemia.
• Severe complications such as myocardial infarction, chronic cardiac insufficiency, hepatic failure, renal insufficiency, etc.
• Clinically uncontrolled active infections.
• Malignant tumors with other progresses.
• Ecg: QT interval > 450 ms.
• Allergic to arsenic agent.
• Pregnant or lactating women.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
incidence and severity of differentiation syndrome	during the induction treatment	All symptoms and signs associated to DS should be paid closely attention to.
complete remission rate	during the induction treatment	complete remission rate after treated by the induction regimen with ATRA and Arsenite

Secondary Outcome Measures

Name	Time	Method
overall survival	from the day of first patient treatment up to 36 months after the last patient's enrollment	from the date of inclusion to date of death, irrespective of cause

Trial Locations

Locations (1)

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