Combined Retinoic Acid,Arsenic Trioxide and Chemo for Newly-diagnosed APL
- Conditions
- Acute Promyelocytic Leukemia
- Interventions
- Drug: ATRA+ArsenicDrug: ATRA+Chemo
- Registration Number
- NCT01987297
- Lead Sponsor
- 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.
- 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still fail to achieve mCR, together with high-risk group who fail to achieve mCR after consolidation therapy will be withdrawn from the study and proceed to salvage treatment.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 738
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ATRA+Arsenic ATRA+Arsenic All low- and intermediate-risk patients receive retinoic acid and arsenic trioxide based consolidation. High-risk patients receive ATRA+Arsenic+Anthracycline consolidation. ATRA+chemo 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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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
Complete remission (CR) rate after induction therapy Blast and promyelocytic leukemia less than 5% in bone marrow
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
Early death (ED) rate 30 days Early death is referred to death within 30 days from the entry into the treatment.
Trial Locations
- Locations (1)
Department of Hematology
🇨🇳Shanghai, China