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

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ClinicalTrials.gov Identifier: NCT01987297
Recruitment Status : Active, not recruiting
First Posted : November 19, 2013
Last Update Posted : August 19, 2019
Sponsor:
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 General 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 of Southern Medical University
The First Affiliated Hospital of Anhui Medical University
Institute of Hematology & Blood Diseases Hospital
Information provided by (Responsible Party):
Jiong HU, Shanghai Jiao Tong University School of Medicine

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.

Condition or disease Intervention/treatment Phase
Acute Promyelocytic Leukemia Drug: ATRA+Arsenic Drug: ATRA+Chemo Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 738 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Combined Retinoic Acid,Arsenic Trioxide and Chemotherapy for Newly-diagnosed Acute Promyelocytic Leukemia: Chinese National Multi-center Randomized Study
Actual Study Start Date : June 2012
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020


Arm Intervention/treatment
Experimental: ATRA+Arsenic
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: 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.

Other Name: retinoic acid + arsenic trioxide

Active Comparator: ATRA+chemo
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

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.

Other Name: retinoic acid + idarubicin or daunorubicin +/- Cytarabine




Primary Outcome Measures :
  1. Disease free survival (DFS) [ Time Frame: 3 year ]
    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 :
  1. Complete remission (CR) rate [ Time Frame: after induction therapy ]
    Blast and promyelocytic leukemia less than 5% in bone marrow

  2. Molecular CR (mCR) [ Time Frame: after consolidation therapy ]
    mCR is defined the absence of detectable PML-RARα transcripts by nested RT-PCR or RQ-PCR in two successive bone marrow samples

  3. Early death (ED) rate [ Time Frame: 30 days ]
    Early death is referred to death within 30 days from the entry into the treatment.

  4. Overall survival (OS) [ Time Frame: 3 years ]
    OS is defined for patients entering the study as time to death of all causes.

  5. Cumulated incidence of relapse (CIR) [ Time Frame: 3 years ]
    CIR is defined for patients having achieved CR as time to any relapse or persistence of PCR positivity after consolidation therapy


Other Outcome Measures:
  1. Hematological or non hematological toxicitytoxicitie [ Time Frame: 3 years ]
    Assessed according to the Common Terminology Criteria for Adverse Events Version 4.0 (National Cancer Institute)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01987297


Locations
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China
Department of Hematology
Shanghai, China, 200025
Sponsors and Collaborators
Shanghai Jiao Tong University School of Medicine
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 General 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 of Southern Medical University
The First Affiliated Hospital of Anhui Medical University
Institute of Hematology & Blood Diseases Hospital
Investigators
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Principal Investigator: Jun-min Li, M.D Department of Hematology, Rui Jin Hospital, Shanghai JiaoTong University School of Medicine

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Responsible Party: Jiong HU, Department of Hematology, Shanghai Jiao Tong University School of Medicine
ClinicalTrials.gov Identifier: NCT01987297     History of Changes
Other Study ID Numbers: APL2012
First Posted: November 19, 2013    Key Record Dates
Last Update Posted: August 19, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Jiong HU, Shanghai Jiao Tong University School of Medicine:
acute promyelocytic leukemia
ATRA
arsenic
Additional relevant MeSH terms:
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Leukemia
Leukemia, Promyelocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Cytarabine
Daunorubicin
Idarubicin
Arsenic Trioxide
Tretinoin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Keratolytic Agents
Dermatologic Agents