Acute Lymphoblastic LeukemiaNCT01678508
Pharmacogenetically Based Dosing of Thiopurines in Childhood Acute Lymphoblastic Leukemia
An observational study of Acute Lymphoblastic Leukemia, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
Trial summary
In a population-based study to explore the impact of TPMT-status on the risk of relapse and of second cancer among all patients treated according to the NOPHO ALL2000. Read more about this study
- Who is it for?
- Ages 1 year to 15 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia
- How many people
- 1,020 participants
- Where
- 1 siteDenmark
- Study dates
- Jan 2002to Feb 2012
- Phase
- Observational
- 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 1 year to 15 years
- All sexes
- No healthy volunteers
- Child
Study population: The study cohort is based on patients enrolled in the NOPHO ALL2000 protocol.
Who may be able to join
- included in the NOPHO ALL2000 protocol
- entered 6-mercaptopurine/Methotrexate maintenance therapy in first remission
- available TPMT phenotype and/or genotype
Who cannot join
- children with Down Syndrome
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacogenetically Based Dosing of Thiopurines in Childhood Acute Lymphoblastic Leukemia - Influence on Cure Rates and Risk of Second Cancer
In a population-based study to explore the impact of TPMT-status on the risk of relapse and of second cancer among all patients treated according to the NOPHO ALL2000.
Read the detailed description
The thiopurines 6-mercaptopurine (6MP) and 6-thioguanine (6TG) are widely used in the treatment of childhood acute lymphoblastic leukemia (ALL). They primarily exert their cytotoxicity through conversion into 6-thioguanine nucleotides (6TGN) that are incorporated into DNA. Interindividual variations in response to thiopurine therapy are influenced by genetically determined polymorphisms in the activity of the enzyme thiopurine methyltransferase (TPMT). TPMT competes with the formation of 6TGN, as it methylates the thiopurines (especially 6MP) and some of their metabolites. Approximately ten percent of all individuals are TPMT heterozygous, with one wild type and one low activity allele, and one in three hundred individuals are TPMT deficient with two low activity alleles. During the maintenance therapy phase of the treatment of childhood ALL, which may last several years, 6MP is given on a daily basis at a starting dose of 75 mg/m.sq./day, which is subsequently adjusted to a white blood cell count of 1.5-3.5 x109/L. We have previously demonstrated that the risk of relapse is reduced by more than 50%, but the risk of second cancer was increased 3-fold among TPMT low activity patients. Accordingly, the Nordic ALL2000 protocol recommended the dosing of 6MP to be based on the patients TPMT activity. In the present study of almost 1000 Nordic patients, we will explore whether this strategy of TPMT-based individualised 6MP dosing have benefitted the patients by reducing their risk of second cancer while preserving their low risk of relapse.
- Conditions
- Acute Lymphoblastic Leukemia
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative risk of relapse and risk of second cancer by Kaplan-Meier analysis with Gray's test comparisons at 10 years
The risks will be reported as percentages.
Measured: Up to 10 years from diagnosis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2012 (estimated)
- Study startJan 2002
- Primary completionJul 2011
- Study completionFeb 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 1,020 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kjeld Schmiegelow, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Kjeld Schmiegelow, M.D., Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01678508
- Sponsor's protocol ID
- NOPHO ALL2000 TPMT and outcome
- Status last verified
- Sep 2012
- First submitted
- 22 May 2012
- Last updated
- 5 Sep 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacogenetically Based Dosing of Thiopurines in Childhood Acute Lymphoblastic Leukemia - Influence on Cure Rates and Risk of Second Cancer
- ClinicalTrials.gov ID
- NCT01678508
- Acronym / sponsor ID
- NOPHO ALL2000 TPMT and outcome
- Conditions
- Acute Lymphoblastic Leukemia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,020 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Study start
- Jan 2002
- Primary completion
- Jul 2011 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 5 Sep 2012 (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 a population-based study to explore the impact of TPMT-status on the risk of relapse and of second cancer among all patients treated according to the NOPHO ALL2000.
Detailed description
The thiopurines 6-mercaptopurine (6MP) and 6-thioguanine (6TG) are widely used in the treatment of childhood acute lymphoblastic leukemia (ALL). They primarily exert their cytotoxicity through conversion into 6-thioguanine nucleotides (6TGN) that are incorporated into DNA. Interindividual variations in response to thiopurine therapy are influenced by genetically determined polymorphisms in the activity of the enzyme thiopurine methyltransferase (TPMT). TPMT competes with the formation of 6TGN, as it methylates the thiopurines (especially 6MP) and some of their metabolites. Approximately ten percent of all individuals are TPMT heterozygous, with one wild type and one low activity allele, and one in three hundred individuals are TPMT deficient with two low activity alleles. During the maintenance therapy phase of the treatment of childhood ALL, which may last several years, 6MP is given on a daily basis at a starting dose of 75 mg/m.sq./day, which is subsequently adjusted to a white blood cell count of 1.5-3.5 x109/L. We have previously demonstrated that the risk of relapse is reduced by more than 50%, but the risk of second cancer was increased 3-fold among TPMT low activity patients. Accordingly, the Nordic ALL2000 protocol recommended the dosing of 6MP to be based on the patients TPMT activity. In the present study of almost 1000 Nordic patients, we will explore whether this strategy of TPMT-based individualised 6MP dosing have benefitted the patients by reducing their risk of second cancer while preserving their low risk of relapse.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 1 year to 15 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- The study cohort is based on patients enrolled in the NOPHO ALL2000 protocol.
Key inclusion criteria (3 listed)
- included in the NOPHO ALL2000 protocol
- entered 6-mercaptopurine/Methotrexate maintenance therapy in first remission
- available TPMT phenotype and/or genotype
Key exclusion criteria (1 listed)
- children with Down Syndrome
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Cumulative risk of relapse and risk of second cancer by Kaplan-Meier analysis with Gray's test comparisons at 10 years
Time frame: Up to 10 years from diagnosis
The risks will be reported as percentages.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2012.
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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.
Kjeld Schmiegelow, M.D. principal investigator
Copenhagen University Hospital, Rigshospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Lymphoblastic Leukemia, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
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 3 inclusion and 1 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: finished, as of the sponsor's last update on 5 Sep 2012. 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 Denmark. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Cumulative risk of relapse and risk of second cancer by Kaplan-Meier analysis with Gray's test comparisons at 10 years (time frame: Up to 10 years from diagnosis). 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 5 Sep 2012.