Optimum Induction Therapy of Low-risk APL

NCT ID: NCT05832320

Last Updated: 2024-05-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2024-12-31

Brief Summary

Despite the high cure probability for acute promyelocytic leukemia (APL), a minority of patients will relapse and the risk factors for relapse are unclear. The goal of this clinical trial is to compare the effectiveness and safety of induction of oral all-trans retinoic acid (ATRA) and realgar-indigo naturalis formula (RIF) combined with oral etoposide or daunorubicin as cytoreductive therapies in low-risk APL. The present study was to explored a cytoreduction of an oral etoposide for low-risk APL with dual induction of ATRA and RIF as a high efficacy, low recurrence, and more convenient all-oral regimen.

Detailed Description

Despite the high cure probability for low-risk acute promyelocytic leukemia (APL) in the all-trans retinoic acid (ATRA) era, several clinical problems lead to treatment failure, including early death (ED) and relapse. Previously studies by our group and others showed a relapse of 1.0-4.8% for low-risk APL, and the median time to hematological relapse was 20.5 months after a hematological complete remission (CR). Dur to the largely unclear mechanisms of relapse, the investigators previously explored that a drop of promyelocytic leukemia retinoic acid receptor alpha (PML-RARA) transcript level at the end of induction therapy was associated with a subsequent risk of relapse. The investigators and others have indicated that the addition of cytarabine in induction therapy might correlate with lower relapse rate. Whether cytoreduction in induction therapy has prognostic significance in APL, besides its role in leukocytosis, remains unclear. Etoposide is a topoisomerase II inhibitor antitumor agent which is widely used in the treatment of several hematological malignancies. The successful experience in high-risk APL demonstrated the efficacy, safety and convenience of oral etoposide as an alternative cytoreductive agent at the initial stage of induction therapy. Therefore, the present prospective study is conducted to explore the potential role of cytoreduction during induction therapy on prognosis, and further exploit the all-oral induction regimen for low-risk APL with etoposide combined with ATRA plus RIF as the front-line therapy for low-risk APL.

Conditions

Acute Promyelocytic Leukemia; Induction Therapy; Oral

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Oral etoposide with dual induction of ATRA and RIF

RIF: 60mg/kg qd, ATRA: 25mg/m2 qd, till CR. When WBC\>4.0×109/L, patients will be given oral etoposide (50mg qd to 50mg tid). Cumulative dosage of etoposide during induction ≤1500mg.

Group Type: EXPERIMENTAL

Etoposide

Intervention Type: DRUG

Introduction: RIF: 60mg/kg qd, ATRA: 25mg/m2 qd, till CR. When WBC\>4.0×109/L, patients will be given oral etoposide (50mg qd to 50mg tid). Cumulative dosage of etoposide during induction ≤1500mg.

Daunorubicin with dual induction of ATRA and RIF

RIF: 60mg/kg qd, ATRA: 25mg/m2 qd, till CR. When WBC\>4.0×109/L, patients will be given daunorubicin (20 to 40mg per dose).

Group Type: ACTIVE_COMPARATOR

Daunorubicin

Intervention Type: DRUG

Introduction: RIF: 60mg/kg qd, ATRA: 25mg/m2 qd, till CR. When WBC\>4.0×109/L, patients will be given daunorubicin (20 to 40mg per dose).

Interventions

Etoposide

Introduction: RIF: 60mg/kg qd, ATRA: 25mg/m2 qd, till CR. When WBC\>4.0×109/L, patients will be given oral etoposide (50mg qd to 50mg tid). Cumulative dosage of etoposide during induction ≤1500mg.

Intervention Type: DRUG

Daunorubicin

Introduction: RIF: 60mg/kg qd, ATRA: 25mg/m2 qd, till CR. When WBC\>4.0×109/L, patients will be given daunorubicin (20 to 40mg per dose).

Intervention Type: DRUG

Other Intervention Names

all-trans retinoic acid; realgar-indigo naturalis formula; all-trans retinoic acid; realgar-indigo naturalis formula

Eligibility Criteria

Inclusion Criteria

• Newly diagnosed APL patients (WHO 2008 diagnostic classification);
• 18-75 years old;
• Liver function: propionate hydrogentransferase (ALT) and aspartate hydrogentransferase (AST) ≤ 2.5 times the upper limit of normal value, bilirubin ≤ 2 times the upper limit of normal value;
• Renal function: muscle salt ≤ 3 times the upper limit of normal value;
• The physical strength score is 0-2 (ECOG);
• White blood cells ≤ 10×109/L;
• Subjects must sign an informed consent form.

Exclusion Criteria

• Subjects who have participated in other clinical trials within 30 days;
• Pregnant and lactating subjects;
• Subjects who are known to be HIV-positive in serological tests;
• Subjects who have viral hepatitis serological test positive;
• Subjects who have severe arrhythmia, abnormal electrocardiogram (QT>500ms);
• Subjects who suffer from mental illness or unable to cooperate with the research treatment and monitoring requirements due to other diseases;
• Subjects who participate in other clinical research at the same time;
• Subjects who fail to sign the informed consent form;
• Other conditions that the researchers think are not suitable for inclusion.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Zhu Xiaolu

Physician-in-charge

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xiaolu Zhu, Doctor

Role: PRINCIPAL_INVESTIGATOR

Peking University People's Hospital

Locations

Peking University Institute of Hematology

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xiaolu Zhu, Doctor

Role: CONTACT

zhuxl0614@163.com

8610-82816999 ext. 8033

Facility Contacts

Xiaolu Zhu, Doctor

Role: primary

zhuxl0614@163.com

8610-82816999 ext. 8033

Other Identifiers

RDL 2022-05

Identifier Type: -

Identifier Source: org_study_id