Acute Promyelocytic LeukemiaPhase 4NCT01987297
Combined Retinoic Acid,Arsenic Trioxide and Chemo for Newly-diagnosed APL
A Phase 4 study testing ATRA+Arsenic and ATRA+Chemo in people with Acute Promyelocytic Leukemia, run by Shanghai Jiao Tong University School of Medicine at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute Promyelocytic Leukemia
- What is being tested?
- ATRA+Arsenic and ATRA+Chemo
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 738 participants
- Where
- 1 siteChina
- Study dates
- Jun 2012to 31 Dec 2020
- Phase
- Phase 4
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: Combined Retinoic Acid,Arsenic Trioxide and Chemotherapy for Newly-diagnosed Acute Promyelocytic Leukemia: Chinese National Multi-center Randomized Study
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.
Read the 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.
- Conditions
- Acute Promyelocytic Leukemia
- Being tested
- ATRA+Arsenic, ATRA+Chemo
- Keywords
- acute promyelocytic leukemia, ATRA, arsenic
- 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.
ATRA+ArsenicDrug
Also called retinoic acid + arsenic trioxide
ATRA: 25mg/m2 daily；Induction: D1 to CR; Consolidation: D1-14 each course; Maintenance: D1-14 each course.
Arsenic: 0.16mg/kg daily. Induction: D1 to CR; Consolidation: low/intermediate-risk patients 28 days each course; high-risk: 14 days each course; Maintenance: 14 days on and off each course.
Idarubicin 8mg/m2 or Daunorubicin 45mg/m2 daily. Induction: 3-4 days in high-risk patients or intermediated-risk patients with leukocytosis developed during induction therapy. Consolidation: 3 days in high-risk patients in first 2 courses.
MTX: 15mg/m2 qw Maintenance: qw x 4 in each course for high-risk patients.
ATRA+ChemoDrug
Also called retinoic acid + idarubicin or daunorubicin +/- Cytarabine
ATRA: 25mg/m2 daily；Induction: D1 to CR; Consolidation: D1-14 each course; Maintenance: D1-14 each course.
Arsenic: 0.16mg/kg daily. Induction: D1 to CR; Maintenance: 14 days on and off each course.
Idarubicin 8mg/m2 or Daunorubicin 45mg/m2 daily. Induction: 3-4 days in high-risk patients or intermediated-risk patients with leukocytosis developed during induction therapy. Consolidation: 3 days in all patients in 2 courses.
Cytarabine: 150mg/m2 or 1g/m2. Consolidation: 150mg/m2 daily x 7 days in high risk patients in first 2 courses; 1g/m2 q12 x 6 doses in third course.
MTX: 15mg/m2 qw Maintenance: qw x4 in each course for high-risk patients.
| Study group | Role | What they receive |
|---|---|---|
| ATRA+Arsenic | Experimental | All low- and intermediate-risk patients receive retinoic acid and arsenic trioxide based consolidation. High-risk patients receive ATRA+Arsenic+Anthracycline consolidation. Receives: Drug: ATRA+Arsenic |
| ATRA+chemo | Active comparator | 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. Receives: Drug: ATRA+Chemo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease free survival (DFS)
DFS is defined for patients having achieve CR as time to relapse either in bone marrow or extra medullary site, or fail to achieve molecular remission, or death of all causes.
Measured: 3 year
Secondary outcomes (5)
Complete remission (CR) rate
Blast and promyelocytic leukemia less than 5% in bone marrow
Measured: after induction therapy
Molecular CR (mCR)
mCR is defined the absence of detectable PML-RARα transcripts by nested RT-PCR or RQ-PCR in two successive bone marrow samples
Measured: after consolidation therapy
Early death (ED) rate
Early death is referred to death within 30 days from the entry into the treatment.
Measured: 30 days
Overall survival (OS)
OS is defined for patients entering the study as time to death of all causes.
Measured: 3 years
Cumulated incidence of relapse (CIR)
CIR is defined for patients having achieved CR as time to any relapse or persistence of PCR positivity after consolidation therapy
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2013 (estimated)
- Study startJun 2012
- Primary completion31 Dec 2020 (estimated)
- Study completion31 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Promyelocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by Shanghai Jiao Tong University School of MedicineThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 738 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Jiao Tong University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Tang-Du Hospital, Peking University People's Hospital, First Affiliated Hospital of Zhejiang University, Tongji Hospital, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, First Hospital of China Medical University, Southwest Hospital, China, West China Hospital, Ningbo No. 1 Hospital, Qilu Hospital of Shandong University, Shandong Provincial Hospital, Union hospital of Fujian Medical University, First Affiliated Hospital of Guangxi Medical University, Guangdong Provincial People's Hospital, First Affiliated Hospital, Sun Yat-Sen University, The First Affiliated Hospital of Soochow University, The First Affiliated Hospital with Nanjing Medical University, The Second Affiliated Hospital of Dalian Medical University, Nanfang Hospital, Southern Medical University, The First Affiliated Hospital of Anhui Medical University, Institute of Hematology & Blood Diseases Hospital, China
- Responsible party
- Principal investigator, Jiong HU, Shanghai Jiao Tong University School of Medicine
- Investigators
- Jun-min Li, M.D, Principal investigator, Department of Hematology, Rui Jin Hospital, Shanghai JiaoTong University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01987297
- Sponsor's protocol ID
- APL2012
- Status last verified
- Aug 2019
- First submitted
- 6 Dec 2012
- Last updated
- 19 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 33495363
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined Retinoic Acid,Arsenic Trioxide and Chemotherapy for Newly-diagnosed Acute Promyelocytic Leukemia: Chinese National Multi-center Randomized Study
- ClinicalTrials.gov ID
- NCT01987297
- Acronym / sponsor ID
- APL2012
- Conditions
- Acute Promyelocytic Leukemia
- Keywords
- acute promyelocytic leukemia, ATRA, arsenic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 738 participants (estimated)
- Lead sponsor
- Shanghai Jiao Tong University School of MedicineUniversity, hospital or other
- Collaborators
- Tang-Du Hospital, Peking University People's Hospital, First Affiliated Hospital of Zhejiang University, Tongji Hospital, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, First Hospital of China Medical University, Southwest Hospital, China, West China Hospital, Ningbo No. 1 Hospital, Qilu Hospital of Shandong University, Shandong Provincial Hospital, Union hospital of Fujian Medical University, First Affiliated Hospital of Guangxi Medical University, Guangdong Provincial People's Hospital, First Affiliated Hospital, Sun Yat-Sen University, The First Affiliated Hospital of Soochow University, The First Affiliated Hospital with Nanjing Medical University, The Second Affiliated Hospital of Dalian Medical University, Nanfang Hospital, Southern Medical University, The First Affiliated Hospital of Anhui Medical University, Institute of Hematology & Blood Diseases Hospital, China
- Study start
- Jun 2012 (actual)
- Primary completion
- 31 Dec 2020 (estimated)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 19 Nov 2013 (estimated)
- 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ATRA+Arsenic | Experimental | Drug: ATRA+ArsenicAll low- and intermediate-risk patients receive retinoic acid and arsenic trioxide based consolidation. High-risk patients receive ATRA+Arsenic+Anthracycline consolidation. |
| ATRA+chemo | Active comparator | Drug: ATRA+ChemoAll 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- 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)
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 |
|---|---|---|
| ATRA+ArsenicAlso: retinoic acid + arsenic trioxideATRA: 25mg/m2 daily；Induction: D1 to CR; Consolidation: D1-14 each course; Maintenance: D1-14 each course. Arsenic: 0.16mg/kg daily. Induction: D1 to CR; Consolidation: low/intermediate-risk patients 28 days each course; high-risk: 14 days each course; Maintenance: 14 days on and off each course. Idarubicin 8mg/m2 or Daunorubicin 45mg/m2 daily. Induction: 3-4 days in high-risk patients or intermediated-risk patients with leukocytosis developed during induction therapy. Consolidation: 3 days in high-risk patients in first 2 courses. MTX: 15mg/m2 qw Maintenance: qw x 4 in each course for high-risk patients. | Drug | ATRA+Arsenic |
| ATRA+ChemoAlso: retinoic acid + idarubicin or daunorubicin +/- CytarabineATRA: 25mg/m2 daily；Induction: D1 to CR; Consolidation: D1-14 each course; Maintenance: D1-14 each course. Arsenic: 0.16mg/kg daily. Induction: D1 to CR; Maintenance: 14 days on and off each course. Idarubicin 8mg/m2 or Daunorubicin 45mg/m2 daily. Induction: 3-4 days in high-risk patients or intermediated-risk patients with leukocytosis developed during induction therapy. Consolidation: 3 days in all patients in 2 courses. Cytarabine: 150mg/m2 or 1g/m2. Consolidation: 150mg/m2 daily x 7 days in high risk patients in first 2 courses; 1g/m2 q12 x 6 doses in third course. MTX: 15mg/m2 qw Maintenance: qw x4 in each course for high-risk patients. | Drug | ATRA+chemo |
Primary outcome
Disease free survival (DFS)
Time frame: 3 year
DFS is defined for patients having achieve CR as time to relapse either in bone marrow or extra medullary site, or fail to achieve molecular remission, or death of all causes.
5 secondary outcomes
Complete remission (CR) rate
Time frame: after induction therapy
Molecular CR (mCR)
Time frame: after consolidation therapy
Early death (ED) rate
Time frame: 30 days
Overall survival (OS)
Time frame: 3 years
Cumulated incidence of relapse (CIR)
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2019.
- Derived from this study: PubMed 33495363Chen 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.
- 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.
Jun-min Li, M.D principal investigator
Department of Hematology, Rui Jin Hospital, Shanghai JiaoTong University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing ATRA+Arsenic and ATRA+Chemo in people with Acute Promyelocytic Leukemia, run by Shanghai Jiao Tong University School of Medicine 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 6 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 19 Aug 2019. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease free survival (DFS) (time frame: 3 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01987297, which also lists 1 linked publication.
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 19 Aug 2019.