Acute Promyelocytic LeukemiaNCT05832320
Optimum Induction Therapy of Low-risk APL
A study testing Etoposide and Daunorubicin in people with Acute Promyelocytic Leukemia and Induction Therapy, run by Peking University People's Hospital at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acute Promyelocytic Leukemia, Induction Therapy, Oral
- What is being tested?
- Etoposide and Daunorubicin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2023to 31 Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Peking University Institute of Hematology
Beijing, Beijing Municipality, 100044
Xiaolu Zhu, Doctor, 8610-82816999 ext. 8033, zhuxl0614@163.com
About this study
Official title: 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.
Read the 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
- Being tested
- Etoposide, Daunorubicin
- Keywords
- Acute Promyelocytic Leukemia, low risk, induction therapy, etoposide
- Medical subject headings
- Leukemia, Promyelocytic, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtoposideDrug
Also called all-trans retinoic acid, realgar-indigo naturalis formula
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.
DaunorubicinDrug
Also called all-trans retinoic acid, realgar-indigo naturalis formula
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).
| Study group | Role | What they receive |
|---|---|---|
| Oral etoposide with dual induction of ATRA and RIF | Experimental | 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. Receives: Drug: Etoposide |
| Daunorubicin with dual induction of ATRA and RIF | Active comparator | 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). Receives: Drug: Daunorubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete remission
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
Measured: 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
PML-RARA transcripts using Abelson tyrosine-protein kinase (ABL) as an internal control by quantitative RT-PCR
Measured: At the end of induction therapy within 45 days after diagnosis
Secondary outcomes (4)
Early death (ED)
Defined as death within 30 days after diagnosis
Measured: During the induction therapy within 30 days after diagnosis
Cumulative recurrence rate
A measure of the total relapse that a certain event will happen during a given period of time
Measured: 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
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.
Measured: 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.
Toxic effects were graded according to the 'WHO classification standard for acute and subacute toxicity of anticancer drugs'.
Measured: From the time of randomization to the time of last follow-up within 2years after diagnosis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2023
- Study start1 Jan 2023
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Promyelocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by Peking University People's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 74 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University People's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhu Xiaolu, Peking University People's Hospital
- Investigators
- Xiaolu Zhu, Doctor, Principal investigator, Peking University People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05832320
- Sponsor's protocol ID
- RDL 2022-05
- Status last verified
- May 2024
- First submitted
- 2 Apr 2023
- Last updated
- 10 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimum Induction Therapy of Low-risk Acute Promyelocytic Leukemia With All Oral Drugs
- ClinicalTrials.gov ID
- NCT05832320
- Acronym / sponsor ID
- RDL 2022-05
- Conditions
- Acute Promyelocytic Leukemia, Induction Therapy, Oral
- Keywords
- Acute Promyelocytic Leukemia, low risk, induction therapy, etoposide
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 74 participants (estimated)
- Lead sponsor
- Peking University People's HospitalUniversity, hospital or other
- Study start
- 1 Jan 2023 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 27 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral etoposide with dual induction of ATRA and RIF | Experimental | Drug: EtoposideRIF: 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 | Active comparator | Drug: DaunorubicinRIF: 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). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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);
Key exclusion criteria (9 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EtoposideAlso: all-trans retinoic acid, realgar-indigo naturalis formulaIntroduction: 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 | Oral etoposide with dual induction of ATRA and RIF |
| DaunorubicinAlso: all-trans retinoic acid, realgar-indigo naturalis formulaIntroduction: 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 with dual induction of ATRA and RIF |
Primary outcome
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
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
4 secondary outcomes
Early death (ED)
Time frame: 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
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
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xiaolu Zhu, Doctor principal investigator
Peking University People's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Etoposide and Daunorubicin in people with Acute Promyelocytic Leukemia and Induction Therapy, run by Peking University People's Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xiaolu Zhu, Doctor (8610-82816999 ext. 8033, zhuxl0614@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete remission (time frame: At the end of induction therapy within 45 days after diagnosis). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2024.