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

Primary Purpose

Acute Promyelocytic Leukemia

Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
ATRA+Arsenic
ATRA+Chemo
Sponsored by
Shanghai Jiao Tong University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Promyelocytic Leukemia focused on measuring acute promyelocytic leukemia, ATRA, arsenic

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department of Hematology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

ATRA+Arsenic

ATRA+chemo

Arm Description

All low- and intermediate-risk patients receive retinoic acid and arsenic trioxide based consolidation. High-risk patients receive ATRA+Arsenic+Anthracycline consolidation.

All low-risk and intermediate-risk patients receive retinoic acid and chemotherapy with idarubicin or daunorubicin as consolidation. High-risk patients receive ATRA+anthracycline and cytarabine as consolidation.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Complete remission (CR) rate
Blast and promyelocytic leukemia less than 5% in bone marrow
Molecular CR (mCR)
mCR is defined the absence of detectable PML-RARα transcripts by nested RT-PCR or RQ-PCR in two successive bone marrow samples
Early death (ED) rate
Early death is referred to death within 30 days from the entry into the treatment.
Overall survival (OS)
OS is defined for patients entering the study as time to death of all causes.
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

Full Information

First Posted
December 6, 2012
Last Updated
August 15, 2019
Sponsor
Shanghai Jiao Tong University School of Medicine
Collaborators
Tang-Du Hospital, Peking University People's Hospital, First Affiliated Hospital of Zhejiang University, Tongji Hospital, Wuhan Union Hospital, China, First Hospital of China Medical University, Southwest Hospital, China, West China Hospital, Ningbo No. 1 Hospital, Qilu Hospital of Shandong University, Shandong Provincial Hospital, Union hospital of Fujian Medical University, First Affiliated Hospital of Guangxi Medical University, Guangdong Provincial People's Hospital, First Affiliated Hospital, Sun Yat-Sen University, The First Affiliated Hospital of Soochow University, The First Affiliated Hospital with Nanjing Medical University, The Second Affiliated Hospital of Dalian Medical University, Nanfang Hospital, Southern Medical University, The First Affiliated Hospital of Anhui Medical University, Institute of Hematology & Blood Diseases Hospital, China
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1. Study Identification

Unique Protocol Identification Number
NCT01987297
Brief Title
Combined Retinoic Acid,Arsenic Trioxide and Chemo for Newly-diagnosed APL
Official Title
Combined Retinoic Acid,Arsenic Trioxide and Chemotherapy for Newly-diagnosed Acute Promyelocytic Leukemia: Chinese National Multi-center Randomized Study
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Unknown status
Study Start Date
June 2012 (Actual)
Primary Completion Date
December 31, 2020 (Anticipated)
Study Completion Date
December 31, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Jiao Tong University School of Medicine
Collaborators
Tang-Du Hospital, Peking University People's Hospital, First Affiliated Hospital of Zhejiang University, Tongji Hospital, Wuhan Union Hospital, China, First Hospital of China Medical University, Southwest Hospital, China, West China Hospital, Ningbo No. 1 Hospital, Qilu Hospital of Shandong University, Shandong Provincial Hospital, Union hospital of Fujian Medical University, First Affiliated Hospital of Guangxi Medical University, Guangdong Provincial People's Hospital, First Affiliated Hospital, Sun Yat-Sen University, The First Affiliated Hospital of Soochow University, The First Affiliated Hospital with Nanjing Medical University, The Second Affiliated Hospital of Dalian Medical University, Nanfang Hospital, Southern Medical University, The First Affiliated Hospital of Anhui Medical University, Institute of Hematology & Blood Diseases Hospital, China

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Promyelocytic Leukemia
Keywords
acute promyelocytic leukemia, ATRA, arsenic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
738 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ATRA+Arsenic
Arm Type
Experimental
Arm Description
All low- and intermediate-risk patients receive retinoic acid and arsenic trioxide based consolidation. High-risk patients receive ATRA+Arsenic+Anthracycline consolidation.
Arm Title
ATRA+chemo
Arm Type
Active Comparator
Arm Description
All low-risk and intermediate-risk patients receive retinoic acid and chemotherapy with idarubicin or daunorubicin as consolidation. High-risk patients receive ATRA+anthracycline and cytarabine as consolidation.
Intervention Type
Drug
Intervention Name(s)
ATRA+Arsenic
Other Intervention Name(s)
retinoic acid + arsenic trioxide
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
ATRA+Chemo
Other Intervention Name(s)
retinoic acid + idarubicin or daunorubicin +/- Cytarabine
Intervention Description
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.
Primary Outcome Measure Information:
Title
Disease free survival (DFS)
Description
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.
Time Frame
3 year
Secondary Outcome Measure Information:
Title
Complete remission (CR) rate
Description
Blast and promyelocytic leukemia less than 5% in bone marrow
Time Frame
after induction therapy
Title
Molecular CR (mCR)
Description
mCR is defined the absence of detectable PML-RARα transcripts by nested RT-PCR or RQ-PCR in two successive bone marrow samples
Time Frame
after consolidation therapy
Title
Early death (ED) rate
Description
Early death is referred to death within 30 days from the entry into the treatment.
Time Frame
30 days
Title
Overall survival (OS)
Description
OS is defined for patients entering the study as time to death of all causes.
Time Frame
3 years
Title
Cumulated incidence of relapse (CIR)
Description
CIR is defined for patients having achieved CR as time to any relapse or persistence of PCR positivity after consolidation therapy
Time Frame
3 years
Other Pre-specified Outcome Measures:
Title
Hematological or non hematological toxicitytoxicitie
Description
Assessed according to the Common Terminology Criteria for Adverse Events Version 4.0 (National Cancer Institute)
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jun-min Li, M.D
Organizational Affiliation
Department of Hematology, Rui Jin Hospital, Shanghai JiaoTong University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Hematology
City
Shanghai
ZIP/Postal Code
200025
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33495363
Citation
Chen L, Zhu HM, Li Y, Liu QF, Hu Y, Zhou JF, Jin J, Hu JD, Liu T, Wu DP, Chen JP, Lai YR, Wang JX, Li J, Li JY, Du X, Wang X, Yang MZ, Yan JS, Ouyang GF, Liu L, Hou M, Huang XJ, Yan XJ, Xu D, Li WM, Li DJ, Lou YJ, Wu ZJ, Niu T, Wang Y, Li XY, You JH, Zhao HJ, Chen Y, Shen Y, Chen QS, Chen Y, Li J, Wang BS, Zhao WL, Mi JQ, Wang KK, Hu J, Chen Z, Chen SJ, Li JM. Arsenic trioxide replacing or reducing chemotherapy in consolidation therapy for acute promyelocytic leukemia (APL2012 trial). Proc Natl Acad Sci U S A. 2021 Feb 9;118(6):e2020382118. doi: 10.1073/pnas.2020382118.
Results Reference
derived

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

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