Combined Retinoic Acid,Arsenic Trioxide and Chemo for Newly-diagnosed APL

Acute Promyelocytic Leukemia Clinical Trial

Official title:

Combined Retinoic Acid,Arsenic Trioxide and Chemotherapy for Newly-diagnosed Acute Promyelocytic Leukemia: Chinese National Multi-center Randomized Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01987297
• Other study ID #: APL2012
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: June 2012
• Est. completion date: December 31, 2020

Study information

• Verified date: August 2019
• Source: Shanghai Jiao Tong University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this prospective randomized study for patients with newly diagnosed acute promyelocytic leukemia, patients will be randomized (1:1) into two groups which receive retinoic acid and arsenic trioxide based treatment versus retinoic acid and chemotherapy based regimen.

Description:

The study is carried out based on Sanz risk stratification of newly-diagnosed APL patients into low-, intermediate- and high-risk groups, and all of them will receive ATRA and ATO as induction therapy (ATRA 25 mg/m2 per day orally + ATO 0.16mg/kg intravenously daily). Anthracycline is added to both high-risk groups or intermediate-risk group with hyperleukocytosis developed during induction therapy but not in low-risk groups.

After achieving CR, patients enter into consolidation therapy. Low-risk patients receive either 2 courses of ATRA plus ATO (Experimental group) or 2 courses of ATRA plus anthracycline chemotherapy (Control group). Intermediate-risk patients receive either 3 courses of ATRA plus ATO (Experimental group) or 2 courses of ATRA plus anthracycline chemotherapy (Control group). Patients of high-risk disease receive 2 courses of ATRA plus ATO and anthracycline and 1 course of ATRA plus ATO treatment (Experimental group) or 2 courses of ATRA plus anthracycline and cytarabine and 1 course of ATRA plus mid-dose cytarabine (Control group).

After consolidation therapy, patients with molecular complete remission (mCR) enter into maintenance therapy. Low- and intermediate-risk patients receive 3 cycles of ATRA and ATO sequential treatment, while those of high-risk receive 5 cycles of ATRA, ATO and methotrexate (MTX) treatment.

For low- and intermediate-risk patients who fail to achieve mCR after consolidation therapy, 3 courses of consolidation therapy of high-risk group will be given with cross-over (i.e. patients in Experimental group received the therapy of Control group, and patients in Control group received the therapy of Experimental group). If patients still fail to achieve mCR, together with high-risk group who fail to achieve mCR after consolidation therapy will be withdrawn from the study and proceed to salvage treatment.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 738
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Newly-diagnosed patients with acute promyelocytic leukemia via cytogenetics and molecular assay

• Age: 18-65

• Hepatic/renal function: Bil=35µmol/L,AST/ALT less than 2Xnormal range, Cr 150µmol/L

• Normal cardial function

• ECOG:0-4

• Informed consent

Exclusion Criteria:

• QTC interval >450ms

• Pregnant or breast feeding patients

• Patients with drug addiction or mental illness

• Patients documented of CNS infiltration at diagnosis

• Patients with severe heart disease (acute myocardial infarction or heart failure)

• Patients with concurrent active malignancy, tuberculosis or HIV infection

• Patients with contraindication or allergy to anthracyclines or other agent in the protocol

• Patients enrolled in other clinical trials

• Patients not apply to the study protocol

Related Conditions & MeSH terms

• Acute Promyelocytic Leukemia
• Leukemia
• Leukemia, Promyelocytic, Acute

Intervention

Drug:
• ATRA+Arsenic
ATRA: 25mg/m2 daily;Induction: D1 to CR; Consolidation: D1-14 each course; Maintenance: D1-14 each course. Arsenic: 0.16mg/kg daily. Induction: D1 to CR; Consolidation: low/intermediate-risk patients 28 days each course; high-risk: 14 days each course; Maintenance: 14 days on and off each course. Idarubicin 8mg/m2 or Daunorubicin 45mg/m2 daily. Induction: 3-4 days in high-risk patients or intermediated-risk patients with leukocytosis developed during induction therapy. Consolidation: 3 days in high-risk patients in first 2 courses. MTX: 15mg/m2 qw Maintenance: qw x 4 in each course for high-risk patients.
• ATRA+Chemo
ATRA: 25mg/m2 daily;Induction: D1 to CR; Consolidation: D1-14 each course; Maintenance: D1-14 each course. Arsenic: 0.16mg/kg daily. Induction: D1 to CR; Maintenance: 14 days on and off each course. Idarubicin 8mg/m2 or Daunorubicin 45mg/m2 daily. Induction: 3-4 days in high-risk patients or intermediated-risk patients with leukocytosis developed during induction therapy. Consolidation: 3 days in all patients in 2 courses. Cytarabine: 150mg/m2 or 1g/m2. Consolidation: 150mg/m2 daily x 7 days in high risk patients in first 2 courses; 1g/m2 q12 x 6 doses in third course. MTX: 15mg/m2 qw Maintenance: qw x4 in each course for high-risk patients.

Locations

Country	Name	City	State
China	Department of Hematology	Shanghai

Sponsors (22)

Lead Sponsor

Collaborator

Shanghai Jiao Tong University School of Medicine

First Affiliated Hospital of Guangxi Medical University, First Affiliated Hospital of Zhejiang University, First Affiliated Hospital, Sun Yat-Sen University, First Hospital of China Medical University, Guangdong General Hospital, Institute of Hematology & Blood Diseases Hospital, Nanfang Hospital of Southern Medical University, Ningbo No. 1 Hospital, Peking University People's Hospital, Qilu Hospital of Shandong University, Shandong Provincial Hospital, Southwest Hospital, China, Tang-Du Hospital, The First Affiliated Hospital of Anhui Medical University, The First Affiliated Hospital of Soochow University, The First Affiliated Hospital with Nanjing Medical University, The Second Affiliated Hospital of Dalian Medical University, Tongji Hospital, Union hospital of Fujian Medical University, West China Hospital, Wuhan Union Hospital, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hematological or non hematological toxicitytoxicitie	Assessed according to the Common Terminology Criteria for Adverse Events Version 4.0 (National Cancer Institute)	3 years
Primary	Disease free survival (DFS)	DFS is defined for patients having achieve CR as time to relapse either in bone marrow or extra medullary site, or fail to achieve molecular remission, or death of all causes.	3 year
Secondary	Complete remission (CR) rate	Blast and promyelocytic leukemia less than 5% in bone marrow	after induction therapy
Secondary	Molecular CR (mCR)	mCR is defined the absence of detectable PML-RARa transcripts by nested RT-PCR or RQ-PCR in two successive bone marrow samples	after consolidation therapy
Secondary	Early death (ED) rate	Early death is referred to death within 30 days from the entry into the treatment.	30 days
Secondary	Overall survival (OS)	OS is defined for patients entering the study as time to death of all causes.	3 years
Secondary	Cumulated incidence of relapse (CIR)	CIR is defined for patients having achieved CR as time to any relapse or persistence of PCR positivity after consolidation therapy	3 years