Leukemia, Lymphocytic, AcutePhase 2NCT00548431
NOPHO ALL-2008 Pilot Study on Consolidation Therapy for Children and Adolescents With Acute Lymphoblastic Leukemia
A Phase 2 study testing 6-mercaptopurine in people with Leukemia, Lymphocytic, Acute, run by Copenhagen University Hospital, Rigshospitalet at 3 sites in 2 countries.
Trial summary
The present pharmacokinetic (PK)-pharmacodynamic (PD) study will explore the toxicity and antileukemic response during the initial 3 months of individualised therapy of children and young adults with acute lymphoblastic leukemia (ALL). Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Leukemia, Lymphocytic, Acute
- What is being tested?
- 6-mercaptopurine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Dec 2007to May 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- B-lineage ALL
- 1-17.9 years
- WBC <100, clinical remission obtained day 2
- Written consent to participation.
Who cannot join
- t(9;22)
- Hypodiploidy
- 11q23-aberrations
- TPMT-deficiency
- Intolerance to MTX or 6MP
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Denmark2 sites
Department of Pediatrics, Rigshospitalet
Copenhagen
Department of Pediatrics, University Hospital
Odense
Sweden1 site
Department of Pediatrics, Drottning Sylvias Pediatric Hospital
Gothenburg
About this study
Official title: Phase II Study of Individual 6-mercaptopurine(6MP) Dose Increments in Children With Acute Lymphoblastic Leukemia (ALL) Receiving High-dose Methotrexate (HDM) and PEG-asparaginase
The present pharmacokinetic (PK)-pharmacodynamic (PD) study will explore the toxicity and antileukemic response during the initial 3 months of individualised therapy of children and young adults with acute lymphoblastic leukemia (ALL). The investigators will on an individual toxicity-titrated basis attempt to increase the dose intensity of the 6-mercaptopurine used in the two-months post-remission treatment phase of lower risk childhood ALL. This will be performed together with continuous PEG-ASP (every 2nd week) and interspersed HD-MTX (5 g/m^2) every 3rd week. Thus, the trial will also test the feasibility of this particular drug combination.
Read the detailed description
In addition to the details above we will also explore
- the relationship of the post-HD-MTX MRD-levels with the dose of 6MP, TPMT-activity, DNA-6TGN, E-6TGN, E-MeMP, E-MTX, and presence of ASP-antibodies,
- the early development of anti-ASP antibodies during continuous PEG-ASP therapy.
The study could improve the understanding of the pharmacodynamics of the 6MP/HD-MTX interaction in combination with PEG-ASP.
- Conditions
- Leukemia, Lymphocytic, Acute
- Being tested
- 6-mercaptopurine
- Keywords
- Leukemia, Lymphocytic, Acute [C04.557.337.428.511], 6-mercaptopurine, methotrexate, asparaginase
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
6-mercaptopurineDrug
Also called PURINETHOL
Standard dose 25 mg/m^2/day. Can be increased up to 75 mg/m^2/day if the myelosuppression is acceptable (ANC>0.5 T-count >50)
| Study group | Role | What they receive |
|---|---|---|
| 6 mercaptopurine arm | Experimental | All patients received basic daily 6MP (6-mercaptopurine) (25 mg/m^2) and in addition high-dose methotrexate(HDM) every 3rd week (3 times HDM in total) and PEG-asparaginase every 14th day. Patients increased the dose of 6MP 2 weeks after each HDM if if the myelotoxicity had been acceptable. This means 2 increments since the study stopped 2 weeks after the last HDM Receives: Drug: 6-mercaptopurine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity of Treatment in Terms of Number of Participants With Serious Adverse Events or Adverse Events, Reported
Number of participants following the protocol treatment for the full consolidation therapy with toxicity in this pilot study trying to individually titrate 6-mercaptopurine to the highest tolerable level during Consolidation.
Measured: 3 months ( 79 days )
Secondary outcomes (1)
Incorporation of 6-thioguanine Nucleotides (6TGN) Into Leukocyte DNA, Development of Asparaginase Antibody Production
Biweekly bloodsamples during the 3 months are analyzed for 6TGN incorporation into leucocyte DNA. In addition Methylated Mercaptopurine (MeMP) and Erythrocyte-Methotrexate level is measured
Measured: During the 3 months consolidation therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2007 (estimated)
- Study startDec 2007
- Primary completionJan 2009
- Study completionMay 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Leukemia, Lymphocytic, AcuteStudies 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 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., Study chair, Pediatric Clinic II, RIgshospitalet, Copenhagen, DK-2100
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00548431
- Sponsor's protocol ID
- NOPHO HDM-6MP pilot study
- Status last verified
- Nov 2016
- First submitted
- 23 Oct 2007
- Last updated
- 9 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Data published (Frandsen et al, Br J Haematol Oct 2011) Anonymised data on individual patients can be provided by study chair (kschmiegelow@rh.dk) including studyno, gender, age, thiopurine methyltransferase status, immunophenotype, white blood cell count at diagnosis, dose increments at time point 1 and 2 for dose adjustment, and dose-limiting toxicities
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Individual 6-mercaptopurine(6MP) Dose Increments in Children With Acute Lymphoblastic Leukemia (ALL) Receiving High-dose Methotrexate (HDM) and PEG-asparaginase
- ClinicalTrials.gov ID
- NCT00548431
- Acronym / sponsor ID
- NOPHO HDM-6MP pilot study
- Conditions
- Leukemia, Lymphocytic, Acute
- Keywords
- Leukemia, Lymphocytic, Acute [C04.557.337.428.511], 6-mercaptopurine, methotrexate, asparaginase
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Study start
- Dec 2007
- Primary completion
- Jan 2009 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 24 Oct 2007 (estimated)
- Results
- Posted 3 Nov 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The present pharmacokinetic (PK)-pharmacodynamic (PD) study will explore the toxicity and antileukemic response during the initial 3 months of individualised therapy of children and young adults with acute lymphoblastic leukemia (ALL). The investigators will on an individual toxicity-titrated basis attempt to increase the dose intensity of the 6-mercaptopurine used in the two-months post-remission treatment phase of lower risk childhood ALL. This will be performed together with continuous PEG-ASP (every 2nd week) and interspersed HD-MTX (5 g/m^2) every 3rd week. Thus, the trial will also test the feasibility of this particular drug combination.
Detailed description
In addition to the details above we will also explore
- the relationship of the post-HD-MTX MRD-levels with the dose of 6MP, TPMT-activity, DNA-6TGN, E-6TGN, E-MeMP, E-MTX, and presence of ASP-antibodies,
- the early development of anti-ASP antibodies during continuous PEG-ASP therapy.
The study could improve the understanding of the pharmacodynamics of the 6MP/HD-MTX interaction in combination with PEG-ASP.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 6 mercaptopurine arm | Experimental | Drug: 6-mercaptopurineAll patients received basic daily 6MP (6-mercaptopurine) (25 mg/m^2) and in addition high-dose methotrexate(HDM) every 3rd week (3 times HDM in total) and PEG-asparaginase every 14th day. Patients increased the dose of 6MP 2 weeks after each HDM if if the myelotoxicity had been acceptable. This means 2 increments since the study stopped 2 weeks after the last HDM |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- B-lineage ALL
- 1-17.9 years
- WBC <100, clinical remission obtained day 2
- Written consent to participation.
Key exclusion criteria (5 listed)
- t(9;22)
- Hypodiploidy
- 11q23-aberrations
- TPMT-deficiency
- Intolerance to MTX or 6MP
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 |
|---|---|---|
| 6-mercaptopurineAlso: PURINETHOLStandard dose 25 mg/m^2/day. Can be increased up to 75 mg/m^2/day if the myelosuppression is acceptable (ANC>0.5 T-count >50) | Drug | 6 mercaptopurine arm |
Primary outcome
Toxicity of Treatment in Terms of Number of Participants With Serious Adverse Events or Adverse Events, Reported
Time frame: 3 months ( 79 days )
Number of participants following the protocol treatment for the full consolidation therapy with toxicity in this pilot study trying to individually titrate 6-mercaptopurine to the highest tolerable level during Consolidation.
1 secondary outcome
Incorporation of 6-thioguanine Nucleotides (6TGN) Into Leukocyte DNA, Development of Asparaginase Antibody Production
Time frame: During the 3 months consolidation therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Data published (Frandsen et al, Br J Haematol Oct 2011) Anonymised data on individual patients can be provided by study chair (kschmiegelow@rh.dk) including studyno, gender, age, thiopurine methyltransferase status, immunophenotype, white blood cell count at diagnosis, dose increments at time point 1 and 2 for dose adjustment, and dose-limiting toxicities
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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. study chair
Pediatric Clinic II, RIgshospitalet, Copenhagen, DK-2100
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 6-mercaptopurine in people with Leukemia, Lymphocytic, Acute, run by Copenhagen University Hospital, Rigshospitalet at 3 sites in 2 countries.
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 4 inclusion and 5 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 9 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 3 sites in Denmark, Sweden. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Nov 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Toxicity of Treatment in Terms of Number of Participants With Serious Adverse Events or Adverse Events, Reported (time frame: 3 months ( 79 days )). 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 9 Jan 2017.