Optimum Induction Therapy of Low-risk APL

April 26, 2023 updated by: Zhu Xiaolu, Peking University People's Hospital

Optimum Induction Therapy of Low-risk Acute Promyelocytic Leukemia With All Oral Drugs

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

74

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100044
        • Recruiting
        • Peking University Institute of Hematology
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: 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.
Other Names:
  • all-trans retinoic acid
  • realgar-indigo naturalis formula
Active Comparator: 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).
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).
Other Names:
  • all-trans retinoic acid
  • realgar-indigo naturalis formula

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete remission
Time Frame: At the end of induction therapy within 45 days after diagnosis
Haematological CR was defined as a proportion of BM blasts of <5%, the absence of blasts in Auer rods, the absence of extramedullary disease, an absolute neutrophil count of >1×10⁹/L and a platelet count of >100×109/L, with no red-cell transfusions
At the end of induction therapy within 45 days after diagnosis
Promyelocytic leukaemia-retinoic acid receptor alpha (PML-RARA) transcript levels of ≥6.5% at the end of induction therapy
Time Frame: At the end of induction therapy within 45 days after diagnosis
PML-RARA transcripts using Abelson tyrosine-protein kinase (ABL) as an internal control by quantitative RT-PCR
At the end of induction therapy within 45 days after diagnosis

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Early death (ED)
Time Frame: During the induction therapy within 30 days after diagnosis
Defined as death within 30 days after diagnosis
During the induction therapy within 30 days after diagnosis
Cumulative recurrence rate
Time Frame: From date of randomization until the date of last documented progression or date of death from any cause, whichever came first, assessed up to 2 years
A measure of the total relapse that a certain event will happen during a given period of time
From date of randomization until the date of last documented progression or date of death from any cause, whichever came first, assessed up to 2 years
2-year event-free survival rate
Time Frame: From the time of randomization to the time of last follow-up within 2 years after diagnosis
The EFS was defined as the time from diagnosis to the following events: no haematological CR after induction therapy; no CMR after consolidation therapy, molecular relapse, haematological relapse; death from any cause; or last follow-up.
From the time of randomization to the time of last follow-up within 2 years after diagnosis
Satefy. Common haematological and non-haematological adverse events were monitored twice per week during induction and twice per month during consolidation.
Time Frame: From the time of randomization to the time of last follow-up within 2years after diagnosis
Toxic effects were graded according to the 'WHO classification standard for acute and subacute toxicity of anticancer drugs'.
From the time of randomization to the time of last follow-up within 2years after diagnosis

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University People's Hospital

Investigators

  • Principal Investigator: Xiaolu Zhu, Doctor, Peking University People's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2023

Primary Completion (Anticipated)

February 28, 2024

Study Completion (Anticipated)

December 31, 2024

Study Registration Dates

First Submitted

April 2, 2023

First Submitted That Met QC Criteria

April 26, 2023

First Posted (Actual)

April 27, 2023

Study Record Updates

Last Update Posted (Actual)

April 27, 2023

Last Update Submitted That Met QC Criteria

April 26, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RDL 2022-05

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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