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

Conditions

Acute Promyelocytic Leukemia

Keywords

acute promyelocytic leukemia, ATRA, arsenic

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still fail to achieve mCR, together with high-risk group who fail to achieve mCR after consolidation therapy will be withdrawn from the study and proceed to salvage treatment.

Li Chen, Hongming Zhu, Fangyi Dong, Yan Li, Qifa Liu et al. (31 authors)

Blood2023-11-022 citations

10.1182/blood-2023-184433

Integration of Genomic and Transcriptomic Markers Improves the Prognosis Prediction of Acute Promyelocytic Leukemia

Xiao-Jing Lin, Q. L. Niu, Yang Shen, Hai Fang, Qing Xue et al. (17 authors)

Clinical Cancer Research2021-04-2326 citations

10.1158/1078-0432.ccr-20-4375

Arsenic trioxide replacing or reducing chemotherapy in consolidation therapy for acute promyelocytic leukemia (APL2012 trial).

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.

2021-02-0140 citations

10.1073/pnas.2020382118

Retinoic Acid and Arsenic Trioxide with or without Chemotherapy for Acute Promyelocytie Leukemia with Different Risk Stratifications: A Interim Analysis of China APL 2012 Study

Junmin Li, Li Chen, Hongming Zhu, Jiong Hu, Bing Chen et al. (20 authors)

Blood2016-12-02

10.1182/blood.v128.22.445.445

Interventions

DRUGATRA+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.

DRUGATRA+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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
Overall survival (OS)	3 years	OS is defined for patients entering the study as time to death of all causes.
Early death (ED) rate	30 days	Early death is referred to death within 30 days from the entry into the treatment.
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
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
Complete remission (CR) rate	after induction therapy	Blast and promyelocytic leukemia less than 5% in bone marrow

Other

Measure	Time frame	Description
Hematological or non hematological toxicitytoxicitie	3 years	Assessed according to the Common Terminology Criteria for Adverse Events Version 4.0 (National Cancer Institute)

Countries

China

Outcome results

None listed