Combined Retinoic Acid,Arsenic Trioxide and Chemo for Newly-diagnosed APL
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| 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still fail to achieve mCR, together with high-risk group who fail to achieve mCR after consolidation therapy will be withdrawn from the study and proceed to salvage treatment.
Study Design
Arms and Interventions
| 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 Names:
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| 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 Names:
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Outcome Measures
Primary Outcome Measures
- Disease free survival (DFS) [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
- Complete remission (CR) rate [after induction therapy]
Blast and promyelocytic leukemia less than 5% in bone marrow
- Molecular CR (mCR) [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
- Early death (ED) rate [30 days]
Early death is referred to death within 30 days from the entry into the treatment.
- Overall survival (OS) [3 years]
OS is defined for patients entering the study as time to death of all causes.
- Cumulated incidence of relapse (CIR) [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
- Hematological or non hematological toxicitytoxicitie [3 years]
Assessed according to the Common Terminology Criteria for Adverse Events Version 4.0 (National Cancer Institute)
Eligibility Criteria
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:
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QTC interval >450ms
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Pregnant or breast feeding patients
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Patients with drug addiction or mental illness
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Patients documented of CNS infiltration at diagnosis
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Patients with severe heart disease (acute myocardial infarction or heart failure)
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Patients with concurrent active malignancy, tuberculosis or HIV infection
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Patients with contraindication or allergy to anthracyclines or other agent in the protocol
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Patients enrolled in other clinical trials
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Patients not apply to the study protocol
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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 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 of Southern Medical University
- The First Affiliated Hospital of Anhui Medical University
- Institute of Hematology & Blood Diseases Hospital
Investigators
- Principal Investigator: Jun-min Li, M.D, Department of Hematology, Rui Jin Hospital, Shanghai JiaoTong University School of Medicine
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- APL2012