Clinical trial NCT01987297: Combined Retinoic Acid,Arsenic Trioxide and Chemo for Newly-diagnosed APL
Official title: Combined Retinoic Acid,Arsenic Trioxide and Chemotherapy for Newly-diagnosed Acute Promyelocytic Leukemia: Chinese National Multi-center Randomized Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Acute Promyelocytic Leukemia
Keywords: acute promyelocytic leukemia
ATRA
arsenic
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
Collaborators: name: Tang-Du Hospital
name: Peking University People's Hospital
name: First Affiliated Hospital of Zhejiang University
name: Tongji Hospital
name: Wuhan Union Hospital, China
name: First Hospital of China Medical University
name: Southwest Hospital, China
name: West China Hospital
name: Ningbo No. 1 Hospital
name: Qilu Hospital of Shandong University
name: Shandong Provincial Hospital
name: Union hospital of Fujian Medical University
name: First Affiliated Hospital of Guangxi Medical University
name: Guangdong Provincial People's Hospital
name: First Affiliated Hospital, Sun Yat-Sen University
name: The First Affiliated Hospital of Soochow University
name: The First Affiliated Hospital with Nanjing Medical University
name: The Second Affiliated Hospital of Dalian Medical University
name: Nanfang Hospital, Southern Medical University
name: The First Affiliated Hospital of Anhui Medical University
name: Institute of Hematology & Blood Diseases Hospital, China
First posted: 2013-11-19
Enrollment: 738
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Disease free survival (DFS)
timeFrame: 3 year
Secondary outcomes:
measure: Complete remission (CR) rate
timeFrame: after induction therapy
measure: Molecular CR (mCR)
timeFrame: after consolidation therapy
measure: Early death (ED) rate
timeFrame: 30 days
measure: Overall survival (OS)
timeFrame: 3 years
measure: Cumulated incidence of relapse (CIR)
timeFrame: 3 years
Other outcomes:
measure: Hematological or non hematological toxicitytoxicitie
timeFrame: 3 years
Locations:
city: Shanghai
country: China
facility: Department of Hematology
Study officials:
affiliation: Department of Hematology, Rui Jin Hospital, Shanghai JiaoTong University School of Medicine
name: Jun-min Li, M.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.