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

NCT01987297 | Unknown Phase 4

• 1 other identifier: APL2012
• Study Type: interventional
• Target: 738
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Promyelocytic Leukemia

Keywords

acute promyelocytic leukemia; ATRA; arsenic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Complete remission (CR) rate

  after induction therapy

• Molecular CR (mCR)

  after consolidation therapy

• Early death (ED) rate

  30 days

• Overall survival (OS)

  3 years

• Cumulated incidence of relapse (CIR)

  3 years

Other Outcomes (1)

• Hematological or non hematological toxicitytoxicitie

  3 years

Study Arms (2)

ATRA+Arsenic

EXPERIMENTAL

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

Drug: ATRA+Arsenic

ATRA+chemo

ACTIVE COMPARATOR

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.

Drug: ATRA+Chemo

Interventions

ATRA+Arsenic DRUG

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.

Also known as: retinoic acid + arsenic trioxide

ATRA+Arsenic

ATRA+Chemo DRUG

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.

Also known as: retinoic acid + idarubicin or daunorubicin +/- Cytarabine

ATRA+chemo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shanghai Jiao Tong University School of Medicine: lead
• Tang-Du Hospital: collaborator
• Peking University People's Hospital: collaborator
• First Affiliated Hospital of Zhejiang University: collaborator
• Tongji Hospital: collaborator
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: collaborator
• First Hospital of China Medical University: collaborator
• Southwest Hospital, China: collaborator
• West China Hospital: collaborator
• Ningbo No. 1 Hospital: collaborator
• Qilu Hospital of Shandong University: collaborator
• Shandong Provincial Hospital: collaborator
• Union hospital of Fujian Medical University: collaborator
• First Affiliated Hospital of Guangxi Medical University: collaborator
• Guangdong Provincial People's Hospital: collaborator
• First Affiliated Hospital, Sun Yat-Sen University: collaborator
• The First Affiliated Hospital of Soochow University: collaborator
• The First Affiliated Hospital with Nanjing Medical University: collaborator
• The Second Affiliated Hospital of Dalian Medical University: collaborator
• Nanfang Hospital, Southern Medical University: collaborator
• The First Affiliated Hospital of Anhui Medical University: collaborator
• Institute of Hematology & Blood Diseases Hospital, China: collaborator

Study Sites (1)

Department of Hematology

Shanghai, 200025, China

Location

Related Publications (1)

• 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.

  PMID: 33495363 DERIVED

MeSH Terms

Conditions

Leukemia, Promyelocytic, Acute

Interventions

Tretinoin; Arsenic Trioxide; Idarubicin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid, Acute; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Jun-min Li, M.D

  Department of Hematology, Rui Jin Hospital, Shanghai JiaoTong University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Hematology

Study Record Dates

• First Submitted: December 6, 2012
• First Posted: November 19, 2013
• Study Start: June 1, 2012
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: August 19, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)