Acute Promyelocytic LeukemiaPhase 3NCT01226303
Treatment Study for Children and Adolescents With Acute Promyelocitic Leukemia
A Phase 3 study testing ATRA and ATRA + IDA in people with Acute Promyelocytic Leukemia, run by Associazione Italiana Ematologia Oncologia Pediatrica at 1 site in Italy.
Trial summary
This study is open to all patients with a diagnosis of acute promyelocytic leukemia (APL) who are PCR positive for the PML-RARα transcript or rarer retinoid sensitive subtypes (i.e. NPM-RAR-alpha, NuMA-RARalpha) and less than 21 years of age (for AIEOP, see appendix A). Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Acute Promyelocytic Leukemia
- What is being tested?
- ATRA and ATRA + IDA
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteItaly
- Study dates
- Jan 2009to Dec 2018
- Phase
- Phase 3
- 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients with a clinical diagnosis of initial APL and subsequently confirmed to have PML-RARα, NPM1-RARα or NUMA-RARα fusion. Whilst this study is only for ATRA-sensitive APL, APL is a hematological emergency and ATRA should be commenced as soon as the diagnosis is suspected. Study entry should not wait until the diagnosis of APL has been confirmed molecularly or cytogenetically
- Less than 21 years of age at initial diagnosis (for AIEOP, see appendix A)
- Considered suitable for anthracycline-based chemotherapy
- Written informed consent available
- Females of childbearing age must have a negative pregnancy test and subsequently must attempt to avoid pregnancy
Who cannot join
- Patients with a clinical diagnosis of APL but subsequently found to have PLZF-RARα fusion or lacking PML-RARα, NPM-RARα or NuMA-RARα rearrangement should be withdrawn from the study and treated on an alternative protocol.
- Refractory/relapsed APL (the guidelines in this protocol for that subgroup are intended for patients treated from initial diagnosis according to this protocol)
- Concurrent active malignancy
- Pregnant or lactating
- Physician and patient/guardian think that intensive chemotherapy is not an appropriate treatment option
- Patients who have received alternative chemotherapy for 7 days or longer without ATRA for any reason (either APL not initially suspected or ATRA not available).
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Dipartimento di Biotecnologie Cellulari ed Ematologia
Roma, 00161
Testi, Dr, 06.857951 ext. +39, testi@bce.uniroma1.it
Annamaria Testi, Dr
About this study
This study is open to all patients with a diagnosis of acute promyelocytic leukemia (APL) who are PCR positive for the PML-RARα transcript or rarer retinoid sensitive subtypes (i.e. NPM-RAR-alpha, NuMA-RARalpha) and less than 21 years of age (for AIEOP, see appendix A).
Read the detailed description
This study is open to all patients with a diagnosis of acute promyelocytic leukemia (APL) who are PCR positive for the PML-RARα transcript or rarer retinoid sensitive subtypes (i.e. NPM-RARalpha, NuMA-RARalpha) and less than 21 years of age (for AIEOP, see appendix A). APL is a rare disease with each national group recruiting small numbers of patients to their trials annually. Therefore this will be an international study expecting to recruit 60-70 patients per annum and a total of 300 patients in 5 years. The study aims to limit the use of anthracyclines and stratify treatment by risk group: standard risk - WBC <10 x 109/l : high risk - WBC ≥10 x 109/l. All-trans retinoic acid (ATRA) is included in all phases of therapy and intermediate dose Ara-C (IDARAC) is given during consolidation treatment. Following one induction course of treatment standard risk patients have 2 consolidation blocks whilst high risk patients have 3 consolidation blocks.
The PML-RARα transcript will be monitored throughout and standard risk patients with detectable minimal residual disease by real time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR+) at the end of the second consolidation block will receive a third consolidation block identical to high risk patients. Patients who are RQ-PCR+ for PML-RARα after completion of the third block of consolidation therapy will be candidates for refractory/relapse treatment, but will remain on study. Refractory/relapsed patients who remain RQ-PCR+ for PML-RARα will be candidates for allogeneic bone marrow transplantation (allo-BMT), whilst those who become RQ-PCR- for PML-RARα will have individualised treatment with ongoing MRD monitoring.
These study guidelines are intended to describe a collaborative international study in APL in children and adolescents and to provide information about procedures for the entry, treatment and follow-up of patients. It is not intended that these guidelines be used as an aide-memoir or guide for the treatment of other patients. Every care has been taken in its drafting, but corrections and amendments may be necessary. Before entering patients into the study, clinicians must ensure that the study has received clearance from their Local Research Ethics Committee and any other necessary body.
- Conditions
- Acute Promyelocytic Leukemia
- Being tested
- ATRA, ATRA + IDA
- 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.
ATRADrug
see the protocol
ATRA + IDADrug
see the protocol
| Study group | Role | What they receive |
|---|---|---|
| standard risk | Experimental | are defined as those patients with a WBC less than 10x10 9 /L at presentation Receives: Drug: ATRA |
| high risk | Active comparator | are defined as those patients whose highest treatment WBC is equal to or greater than 10x10 9 /L at presentation Receives: Drug: ATRA + IDA |
What is being measured
The primary outcome is the main question the study is designed to answer.
• to conduct an international pediatric study for APL based on the GIMEMA-AIEOP/AIDA 93 protocol (the study from the Italian GIMEMA -AIEOP group which has produced the best results in children with APL to date), with optimal outcome and less toxicity
- to conduct an international pediatric study for APL based on the GIMEMA-AIEOP/AIDA 93 protocol (the study from the Italian GIMEMA -AIEOP group which has produced the best results in children with APL to date), with optimal outcome and less toxicity
Measured: 5 years
Secondary outcomes (1)
• To monitor cardiotoxicity by echocardiography
- To monitor cardiotoxicity by echocardiography
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2010 (estimated)
- Study startJan 2009
- Primary completionJun 2017 (estimated)
- Study completionDec 2018 (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.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Associazione Italiana Ematologia Oncologia Pediatrica
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Annamaria Testi, Dr, Principal investigator, Associazione Italiana Ematologia Oncologia Pediatrica
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01226303
- Sponsor's protocol ID
- ICC APL STUDY 01
- Status last verified
- Jul 2016
- First submitted
- 20 Oct 2010
- Last updated
- 26 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment Study for Children and Adolescents With Acute Promyelocitic Leukemia
- ClinicalTrials.gov ID
- NCT01226303
- Acronym / sponsor ID
- ICC APL STUDY 01
- Conditions
- Acute Promyelocytic Leukemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Associazione Italiana Ematologia Oncologia PediatricaUniversity, hospital or other
- Study start
- Jan 2009
- Primary completion
- Jun 2017 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 22 Oct 2010 (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.
This study is open to all patients with a diagnosis of acute promyelocytic leukemia (APL) who are PCR positive for the PML-RARα transcript or rarer retinoid sensitive subtypes (i.e. NPM-RAR-alpha, NuMA-RARalpha) and less than 21 years of age (for AIEOP, see appendix A).
Detailed description
This study is open to all patients with a diagnosis of acute promyelocytic leukemia (APL) who are PCR positive for the PML-RARα transcript or rarer retinoid sensitive subtypes (i.e. NPM-RARalpha, NuMA-RARalpha) and less than 21 years of age (for AIEOP, see appendix A). APL is a rare disease with each national group recruiting small numbers of patients to their trials annually. Therefore this will be an international study expecting to recruit 60-70 patients per annum and a total of 300 patients in 5 years. The study aims to limit the use of anthracyclines and stratify treatment by risk group: standard risk - WBC <10 x 109/l : high risk - WBC ≥10 x 109/l. All-trans retinoic acid (ATRA) is included in all phases of therapy and intermediate dose Ara-C (IDARAC) is given during consolidation treatment. Following one induction course of treatment standard risk patients have 2 consolidation blocks whilst high risk patients have 3 consolidation blocks.
The PML-RARα transcript will be monitored throughout and standard risk patients with detectable minimal residual disease by real time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR+) at the end of the second consolidation block will receive a third consolidation block identical to high risk patients. Patients who are RQ-PCR+ for PML-RARα after completion of the third block of consolidation therapy will be candidates for refractory/relapse treatment, but will remain on study. Refractory/relapsed patients who remain RQ-PCR+ for PML-RARα will be candidates for allogeneic bone marrow transplantation (allo-BMT), whilst those who become RQ-PCR- for PML-RARα will have individualised treatment with ongoing MRD monitoring.
These study guidelines are intended to describe a collaborative international study in APL in children and adolescents and to provide information about procedures for the entry, treatment and follow-up of patients. It is not intended that these guidelines be used as an aide-memoir or guide for the treatment of other patients. Every care has been taken in its drafting, but corrections and amendments may be necessary. Before entering patients into the study, clinicians must ensure that the study has received clearance from their Local Research Ethics Committee and any other necessary body.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| standard risk | Experimental | Drug: ATRAare defined as those patients with a WBC less than 10x10 9 /L at presentation |
| high risk | Active comparator | Drug: ATRA + IDAare defined as those patients whose highest treatment WBC is equal to or greater than 10x10 9 /L at presentation |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Patients with a clinical diagnosis of initial APL and subsequently confirmed to have PML-RARα, NPM1-RARα or NUMA-RARα fusion. Whilst this study is only for ATRA-sensitive APL, APL is a hematological emergency and ATRA should be commenced as soon as the diagnosis is suspected. Study entry should not wait until the diagnosis of APL has been confirmed molecularly or cytogenetically
- Less than 21 years of age at initial diagnosis (for AIEOP, see appendix A)
- Considered suitable for anthracycline-based chemotherapy
- Written informed consent available
- Females of childbearing age must have a negative pregnancy test and subsequently must attempt to avoid pregnancy
Key exclusion criteria (6 listed)
- Patients with a clinical diagnosis of APL but subsequently found to have PLZF-RARα fusion or lacking PML-RARα, NPM-RARα or NuMA-RARα rearrangement should be withdrawn from the study and treated on an alternative protocol.
- Refractory/relapsed APL (the guidelines in this protocol for that subgroup are intended for patients treated from initial diagnosis according to this protocol)
- Concurrent active malignancy
- Pregnant or lactating
- Physician and patient/guardian think that intensive chemotherapy is not an appropriate treatment option
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 |
|---|---|---|
| ATRAsee the protocol | Drug | standard risk |
| ATRA + IDAsee the protocol | Drug | high risk |
Primary outcome
• to conduct an international pediatric study for APL based on the GIMEMA-AIEOP/AIDA 93 protocol (the study from the Italian GIMEMA -AIEOP group which has produced the best results in children with APL to date), with optimal outcome and less toxicity
Time frame: 5 years
• to conduct an international pediatric study for APL based on the GIMEMA-AIEOP/AIDA 93 protocol (the study from the Italian GIMEMA -AIEOP group which has produced the best results in children with APL to date), with optimal outcome and less toxicity
1 secondary outcome
• To monitor cardiotoxicity by echocardiography
Time frame: 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2017.
- Italian association of Pediatric Hematology and OncologyLink provided by the sponsor.
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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.
Annamaria Testi, Dr principal investigator
Associazione Italiana Ematologia Oncologia Pediatrica
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ATRA and ATRA + IDA in people with Acute Promyelocytic Leukemia, run by Associazione Italiana Ematologia Oncologia Pediatrica at 1 site in Italy.
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 5 inclusion and 6 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 26 Jan 2017. 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 Italy. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Contact Annamaria Testi, PI (06.857951 ext. +39, testi@bce.uniroma1.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
• to conduct an international pediatric study for APL based on the GIMEMA-AIEOP/AIDA 93 protocol (the study from the Italian GIMEMA -AIEOP group which has produced the best results in children with APL to date), with optimal outcome and less toxicity (time frame: 5 years). 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 26 Jan 2017.