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

Shanghai Jiao Tong University School of Medicine

Status and phase: Unknown; Phase 4

Conditions: Acute Promyelocytic Leukemia

Treatments: Drug: ATRA+Chemo; Drug: ATRA+Arsenic

Study type: Interventional

Funder types: Other

Identifiers

NCT01987297

APL2012

Details and patient eligibility

About

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.

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still fail to achieve mCR, together with high-risk group who fail to achieve mCR after consolidation therapy will be withdrawn from the study and proceed to salvage treatment.

Enrollment: 738 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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738 participants in 2 patient groups

ATRA+Arsenic

Experimental group

Description:

All low- and intermediate-risk patients receive retinoic acid and arsenic trioxide based consolidation. High-risk patients receive ATRA+Arsenic+Anthracycline consolidation.

Treatment:

Drug: ATRA+Arsenic

ATRA+chemo

Active Comparator group

Description:

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.

Treatment:

Drug: ATRA+Chemo