Acute Lymphoblastic LeukemiaPhase 4NCT01906671
Study on Two Different Formulations of 6-mercaptopurine. Tablet Versus Oral Liquid
A Phase 4 study testing Xaluprine and Puri-Nethol in people with Acute Lymphoblastic Leukemia and 6-mercaptopurine Therapy, run by Kjeld Schmiegelow at 1 site in Denmark.
Trial summary
Acute lymphoblastic leukemia (ALL) accounts for 30 % of all childhood malignancies. The patients undergo four phases of treatment, finishing with a late maintenance phase in which 6-mercaptopurine and Methotrexate are essential components. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, 6-mercaptopurine Therapy
- What is being tested?
- Xaluprine and Puri-Nethol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteDenmark
- Study dates
- Jun 2013to Nov 2018
- 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 Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Childhood acute lymphoblastic leukemia patients, age 0-18 years at diagnosis, treated at the department of pediatrics and adolescent medicine, Rigshospitalet.
- Informed consent
Who cannot join
- None
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
Juliane Marie Centret, Rigshospitalet
Copenhagen, DK-, 2100
Kjeld Schmiegelow, Professor, +45 35451357, kjeld.schmiegelow@regionh.dk
Rikke Hebo Larsen, MD, +45 35457932, rikke.hebo.larsen.01@regionh.dk
About this study
Official title: Plasma Kinetics of Tablet and Liquid Formulations of 6-mercaptopurine in Childhood Acute Lymphoblastic Leukemia.
Acute lymphoblastic leukemia (ALL) accounts for 30 % of all childhood malignancies. The patients undergo four phases of treatment, finishing with a late maintenance phase in which 6-mercaptopurine and Methotrexate are essential components. Insufficient treatment intensity in this phase is associated with increased risk of relapse. Excessive variation in the bioavailability of 6-mercaptopurine has been observed which can cause both risks of undertreatment/relapse as well as overtreatment with severe side effects.
In the attempt to achieve individualized 6-mercaptopurine dosing different approaches have been pursued. Nonetheless variation in bioavailability remains a problem.
Read more
Earlier, oral tablets of 50 mg (Purinethol) were the only administration form of 6-mercaptopurine and it was primarily designed for adult patients. Challenges with accurate dosing and getting the children to swallow the tablets have been a widespread problem, forcing the caregivers to divide or crush the tablets as well as having to administer different dosages over 2-3 days. Due to these problems, an oral liquid formulation of 6-mercaptopurine (Xaluprine) has been developed. However this oral liquid has only been tested on healthy adult volunteers, and not on the target group, childhood patients. This project will assess the bioavailability and plasma kinetics of oral liquid and tablet formulation of 6-mercaptopurine in children with acute lymphoblastic leukemia.
The investigators hypothesize to observe comparable plasma kinetics, in children with acute lymphoblastic leukemia when treated with 6-mercaptopurine in the form of a tablet and oral liquid formulation, as previously observed in healthy adults.
- Being tested
- Xaluprine, Puri-Nethol
- Keywords
- 6-mercaptopurine, Drug formulation
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XaluprineDrug
Comparison of plasma kinetics after administration of 6-mercaptopurine in the form of a tablet (Puri-Nethol) and in the form of an oral liquid formulation (Xaluprine). Each patient will be included in both arms of the study, because of the cross-over design.
Puri-NetholDrug
Comparison of plasma kinetics after administration of 6-mercaptopurine in the form of a tablet (Puri-Nethol) and in the form of an oral liquid formulation (Xaluprine). Each patient will be included in both arms of the study, because of the cross-over design.
| Study group | Role | What they receive |
|---|---|---|
| Puri-Nethol | Experimental | Tablet formulation of 6-mercaptopurine Receives: Drug: Xaluprine; Drug: Puri-Nethol |
| Xaluprine | Experimental | Oral liquid formulation of 6-mercaptopurine Receives: Drug: Xaluprine; Drug: Puri-Nethol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to maximum concentration (Tmax)
Time to maximum concentration (Tmax)
Measured: Will be measured within a six months after collection of the blood samples
Secondary outcomes (3)
Area under curve(AUC)
Area under curve(AUC)
Measured: Will be measured within six months after collection of the blood samples
Maximum concentration (Cmax)
Maximum concentration (Cmax)
Measured: Will be measured within six months after collection of the blood samples
Time to half-life (T½)
Time to half-life (T½)
Measured: Will be measured within six months after collection of the blood samples
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2013 (estimated)
- Study startJun 2013
- Primary completionSep 2018 (estimated)
- Study completionNov 2018 (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 Lymphoblastic 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kjeld Schmiegelow
- Sponsor type
- University, hospital or other
- Collaborators
- Danish Cancer Society
- Responsible party
- Sponsor-investigator, Kjeld Schmiegelow, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Kjeld Schmiegelow, Professor, Principal investigator, Pediatric Clinic II, Rigshospitalet, Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01906671
- Sponsor's protocol ID
- 6-MP formulation
- Other IDs
- 2013-001236-21
- Status last verified
- Apr 2018
- First submitted
- 16 Jul 2013
- Last updated
- 20 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Larsen RH, Hjalgrim LL, Grell K, Kristensen K, Pedersen LG, Brunner ED, Als-Nielsen B, Schmiegelow K, Nersting J. Pharmacokinetics of tablet and liquid formulations of oral 6-mercaptopurine in children with acute lymphoblastic leukemia. Cancer Chemother Pharmacol. 2020 Jul;86(1):25-32. doi: 10.1007/s00280-020-04097-x. Epub 2020 Jun 9.
PubMed 32519032
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Plasma Kinetics of Tablet and Liquid Formulations of 6-mercaptopurine in Childhood Acute Lymphoblastic Leukemia.
- ClinicalTrials.gov ID
- NCT01906671
- Acronym / sponsor ID
- 6-MP formulation
- Keywords
- 6-mercaptopurine, Drug formulation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Kjeld SchmiegelowUniversity, hospital or other
- Collaborators
- Danish Cancer Society
- Study start
- Jun 2013 (actual)
- Primary completion
- Sep 2018 (estimated)
- Study completion
- Nov 2018 (estimated)
- First posted
- 24 Jul 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.
Acute lymphoblastic leukemia (ALL) accounts for 30 % of all childhood malignancies. The patients undergo four phases of treatment, finishing with a late maintenance phase in which 6-mercaptopurine and Methotrexate are essential components. Insufficient treatment intensity in this phase is associated with increased risk of relapse. Excessive variation in the bioavailability of 6-mercaptopurine has been observed which can cause both risks of undertreatment/relapse as well as overtreatment with severe side effects.
In the attempt to achieve individualized 6-mercaptopurine dosing different approaches have been pursued. Nonetheless variation in bioavailability remains a problem.
Earlier, oral tablets of 50 mg (Purinethol) were the only administration form of 6-mercaptopurine and it was primarily designed for adult patients. Challenges with accurate dosing and getting the children to swallow the tablets have been a widespread problem, forcing the caregivers to divide or crush the tablets as well as having to administer different dosages over 2-3 days. Due to these problems, an oral liquid formulation of 6-mercaptopurine (Xaluprine) has been developed. However this oral liquid has only been tested on healthy adult volunteers, and not on the target group, childhood patients. This project will assess the bioavailability and plasma kinetics of oral liquid and tablet formulation of 6-mercaptopurine in children with acute lymphoblastic leukemia.
The investigators hypothesize to observe comparable plasma kinetics, in children with acute lymphoblastic leukemia when treated with 6-mercaptopurine in the form of a tablet and oral liquid formulation, as previously observed in healthy adults.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Puri-Nethol | Experimental | Drug: Xaluprine, Drug: Puri-NetholTablet formulation of 6-mercaptopurine |
| Xaluprine | Experimental | Drug: Xaluprine, Drug: Puri-NetholOral liquid formulation of 6-mercaptopurine |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Childhood acute lymphoblastic leukemia patients, age 0-18 years at diagnosis, treated at the department of pediatrics and adolescent medicine, Rigshospitalet.
- Informed consent
Key exclusion criteria (1 listed)
- None
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 |
|---|---|---|
| XaluprineComparison of plasma kinetics after administration of 6-mercaptopurine in the form of a tablet (Puri-Nethol) and in the form of an oral liquid formulation (Xaluprine). Each patient will be included in both arms of the study, because of the cross-over design. | Drug | Puri-Nethol, Xaluprine |
| Puri-NetholComparison of plasma kinetics after administration of 6-mercaptopurine in the form of a tablet (Puri-Nethol) and in the form of an oral liquid formulation (Xaluprine). Each patient will be included in both arms of the study, because of the cross-over design. | Drug | Puri-Nethol, Xaluprine |
Primary outcome
Time to maximum concentration (Tmax)
Time frame: Will be measured within a six months after collection of the blood samples
Time to maximum concentration (Tmax)
3 secondary outcomes
Area under curve(AUC)
Time frame: Will be measured within six months after collection of the blood samples
Maximum concentration (Cmax)
Time frame: Will be measured within six months after collection of the blood samples
Time to half-life (T½)
Time frame: Will be measured within six months after collection of the blood samples
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2018.
- Derived from this study: PubMed 32519032Larsen RH, Hjalgrim LL, Grell K, Kristensen K, Pedersen LG, Brunner ED, Als-Nielsen B, Schmiegelow K, Nersting J. Pharmacokinetics of tablet and liquid formulations of oral 6-mercaptopurine in children with acute lymphoblastic leukemia. Cancer Chemother Pharmacol. 2020 Jul;86(1):25-32. doi: 10.1007/s00280-020-04097-x. Epub 2020 Jun 9.
- Individual participant dataSharing planned: Undecided
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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, Professor principal investigator
Pediatric Clinic II, Rigshospitalet, Copenhagen
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 Xaluprine and Puri-Nethol in people with Acute Lymphoblastic Leukemia and 6-mercaptopurine Therapy, run by Kjeld Schmiegelow 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 2 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: status not confirmed, as of the sponsor's last update on 20 Apr 2018. 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.
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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to maximum concentration (Tmax) (time frame: Will be measured within a six months after collection of the blood samples). 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 NCT01906671, 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 20 Apr 2018.