Lymphoblastic Leukemia, Acute, ChildhoodPhase 2NCT03022747
Optimizing 6-mercaptopurine Therapy in Pediatric Acute Lymphoblastic Leukemia by Using Allopurinol
A Phase 2 study testing Allopurinol and Standard treatment in people with Lymphoblastic Leukemia, Acute, Childhood, run by Vastra Gotaland Region at 3 sites in 2 countries.
Trial summary
The study will investigate, in children with acute lymphoblastic leukemia during maintenance treatment, if addition of allopurinol to conventional oral 6-mercaptopurine and methotrexate therapy, affects erythrocyte concentrations of 6-thioguanine and 6 methylmercaptopurine. Read more about this study
- Who is it for?
- Ages 6 months to 19 years
- Conditions the study is for
- Lymphoblastic Leukemia, Acute, Childhood
- What is being tested?
- Allopurinol and Standard treatment
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Jan 2017to Apr 2019
- Phase
- Phase 2
- 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 6 months to 19 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Confirmed diagnosis of acute lymphoblastic leukemia
- Treatment according to Nordic Society for pediatric hematology/oncology (NOPHO) ALL2008 based protocols
- Age 0-18y at time of initial diagnosis
- TPMT wild type
- Written informed consent
Who cannot join
- Mature B cell lymphoblastic leukemia
- t(9;22) positive acute lymphoblastic leukemia
- Unknown TPMT status or presence of TPMT mutation (both heterozygous and homozygous)
- Known intolerance to any of the chemotherapeutic drugs in the protocol
- Major organ failure precluding administration of planned chemotherapy
- Severe liver toxicity defined as persistent (≥ two weeks) elevation of either S-bilirubin > 50 μmol/l or S-GPT > 20 x Upper normal limit (UNL) or P-Prothrombin complex > 1.5.
- Reduced kidney function defined as S-creatinine ≥ 1.5 x UNL.
- Lactating female or female of childbearing potential not using adequate contraception.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Sweden2 sites, 2 recruiting
- Recruiting
Childrens' Cancer Centre, Queen Silvias Childrens and Adolescents Hospital
Gothenburg, 416 85
Lene Karlsson, MD, +46 313435610, lene.karlsson@vgregion.se
- Not yet recruiting
Linköping University Hospital, Dept of Pediatrics
Linköping, 58185
Hartmut Vogt, MD, PhD, +46 101031343, hartmut.vogt@regionostergotland.se
Finland1 site, 1 recruiting
- Not yet recruiting
Dept of Pediatrics and Adolescents, Oulu University Hospital, Box 23, 90029 OYS, Finland
Oulu, 90029 OYS
Riita Niinimäki, MD, PhD, +358 8 3155832, riita.niinimaki@ppshp.fi
About this study
Official title: Optimizing 6-mercaptopurine Therapy in Pediatric Acute Lymphoblastic Leukemia by Using Allopurinol Clinical Study in Children 1-19 Years on Maintenance Therapy for Acute Lymphoblastic Leukemia.
The study will investigate, in children with acute lymphoblastic leukemia during maintenance treatment, if addition of allopurinol to conventional oral 6-mercaptopurine and methotrexate therapy, affects erythrocyte concentrations of 6-thioguanine and 6 methylmercaptopurine. The effect on hematological and liver toxicity parameters in blood will also be investigated as well as clinical toxicity.
Read the detailed description
After one month of conventional maintenance therapy (MT) children and adolescents, treated for acute lymphoblastic leukemia on Nordic protocols and with wild type thiopurine methyltransferase (TPMT) are eligible for the study. They will first receive a 12 week phase with normal MT during which time repeated sampling of 6-mercaptopurine (6MP) metabolite levels and other laboratory parameters will be performed. After 12 weeks, allopurinol at a dose of 50 mg/sqm is added (simultaneously reducing the dose of 6MP by 50%) and during the next 12 weeks patients are monitored closely for toxicity and samples for determination of metabolite levels and hematological and liver toxicity are obtained regularly. If, after 4 weeks of allopurinol treatment, the levels of 6-thioguanine are below 200 nmol/mmol hemoglobin, the dose of allopurinol will be increased to 100 mg/sqm. Allopurinol treatment is continued for 12 weeks after which the patients switch to their original maintenance therapy.
- Conditions
- Lymphoblastic Leukemia, Acute, Childhood
- Being tested
- Allopurinol, Standard treatment
- 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.
AllopurinolDrug
Allopurinol is added to standard oral 6-mercaptopurine and methotrexate
Oral 6-mercaptopurine and methotrexate
| Study group | Role | What they receive |
|---|---|---|
| Standard maintenance therapy | Active comparator | Standard maintenance therapy with 6 mercaptopurine and methotrexate Receives: Drug: Standard treatment |
| Allopurinol treatment | Experimental | The second 12 week phase during which allopurinol is added to oral 6-mercaptopurine and methotrexate therapy Receives: Drug: Allopurinol |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-thioguanine (6TG) levels in erythrocytes
The fraction of patients with 6TG levels over 200 nmol/mmol Hb at week 13 and 25 (ie after 12 weeks standard and allopurinol treatment respectively)
Measured: Up to week 25
Secondary outcomes (13)
Mean level of 6-thioguanine
The mean level of 6TG at week 13 and 25
Measured: Up to week 25
Mean level of DNA-incorporated thioguanine (DNA-TGN)
The mean level of DNA-TGN at week 13 and 25
Measured: Up to week 25
Mean level of 6-methylmercaptopurine (6MMP)
The mean level of 6MMP at week 13 and 25
Measured: Up to week 25
Mean levels of platelets
Comparison of weighted mean of platelets in the treatment phases
Measured: Up to week 25
Mean levels of hemoglobin
Comparison of weighted mean of hemoglobin in the treatment phases
Measured: Up to week 25
Mean levels of absolute neutrophil count (ANC)
Comparison of weighted mean of ANC in the treatment phases
Measured: Up to week 25
Mean levels of white blood cells (WBC)
Comparison of weighted mean of WBC in the treatment phases
Measured: Up to week 25
Glutamate pyruvate transaminase (GPT)
Comparison of weighted means of serum GPT in the treatment phases
Measured: Up to week 25
Bilirubin
Comparison of weighted means of serum bilirubin in the treatment phases
Measured: Up to week 25
Hypoglycemia
Comparison of incidence of hypoglycemia and laboratory measures of metabolic disturbance during the treatment phases
Measured: Up to week 25
Metabolic disturbance
Comparison of incidence of laboratory measures of metabolic disturbance during the treatment phases
Measured: Up to week 25
Incidence of serious adverse events (SAE)
Comparison of the frequency of SAE in the treatment phases
Measured: Up to week 29
Cumulative dose of 6-mercaptopurine and methotrexate
Comparison of the cumulative dose of 6MP and methotrexate and days with treatment interruption in the two treatment arms
Measured: Up to week 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2017 (estimated)
- Study startJan 2017
- Primary completionDec 2018 (estimated)
- Study completionApr 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lymphoblastic Leukemia, Acute, ChildhoodStudies of the same condition, open and under way.
- More trials run by Vastra Gotaland RegionThe 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
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vastra Gotaland Region
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Jonas Abrahamsson, PhD, MD, Study chair, Childrens Cancer Center, Queen Silvia Children Hospital, Sahlgrenska Academy, Gothenburg, SwedenRiita Niinimäki, PhD, MD, Principal investigator, Dept of Pediatrics and Adolescents, Oulu University Hospital, Box 23, 90029 OYS, Finland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03022747
- Sponsor's protocol ID
- Allopurinol Study V3.0
- Status last verified
- Jan 2017
- First submitted
- 9 Jan 2017
- Last updated
- 16 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimizing 6-mercaptopurine Therapy in Pediatric Acute Lymphoblastic Leukemia by Using Allopurinol Clinical Study in Children 1-19 Years on Maintenance Therapy for Acute Lymphoblastic Leukemia.
- ClinicalTrials.gov ID
- NCT03022747
- Acronym / sponsor ID
- Allopurinol Study V3.0
- Conditions
- Lymphoblastic Leukemia, Acute, Childhood
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Vastra Gotaland RegionOther government
- Study start
- Jan 2017
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Apr 2019 (estimated)
- First posted
- 16 Jan 2017 (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.
The study will investigate, in children with acute lymphoblastic leukemia during maintenance treatment, if addition of allopurinol to conventional oral 6-mercaptopurine and methotrexate therapy, affects erythrocyte concentrations of 6-thioguanine and 6 methylmercaptopurine. The effect on hematological and liver toxicity parameters in blood will also be investigated as well as clinical toxicity.
Detailed description
After one month of conventional maintenance therapy (MT) children and adolescents, treated for acute lymphoblastic leukemia on Nordic protocols and with wild type thiopurine methyltransferase (TPMT) are eligible for the study. They will first receive a 12 week phase with normal MT during which time repeated sampling of 6-mercaptopurine (6MP) metabolite levels and other laboratory parameters will be performed. After 12 weeks, allopurinol at a dose of 50 mg/sqm is added (simultaneously reducing the dose of 6MP by 50%) and during the next 12 weeks patients are monitored closely for toxicity and samples for determination of metabolite levels and hematological and liver toxicity are obtained regularly. If, after 4 weeks of allopurinol treatment, the levels of 6-thioguanine are below 200 nmol/mmol hemoglobin, the dose of allopurinol will be increased to 100 mg/sqm. Allopurinol treatment is continued for 12 weeks after which the patients switch to their original maintenance therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard maintenance therapy | Active comparator | Drug: Standard treatmentStandard maintenance therapy with 6 mercaptopurine and methotrexate |
| Allopurinol treatment | Experimental | Drug: AllopurinolThe second 12 week phase during which allopurinol is added to oral 6-mercaptopurine and methotrexate therapy |
Who may qualify
- Ages
- 6 months to 19 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Confirmed diagnosis of acute lymphoblastic leukemia
- Treatment according to Nordic Society for pediatric hematology/oncology (NOPHO) ALL2008 based protocols
- Age 0-18y at time of initial diagnosis
- TPMT wild type
- Written informed consent
Key exclusion criteria (8 listed)
- Mature B cell lymphoblastic leukemia
- t(9;22) positive acute lymphoblastic leukemia
- Unknown TPMT status or presence of TPMT mutation (both heterozygous and homozygous)
- Known intolerance to any of the chemotherapeutic drugs in the protocol
- Major organ failure precluding administration of planned chemotherapy
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 |
|---|---|---|
| AllopurinolAllopurinol is added to standard oral 6-mercaptopurine and methotrexate | Drug | Allopurinol treatment |
| Standard treatmentOral 6-mercaptopurine and methotrexate | Drug | Standard maintenance therapy |
Primary outcome
6-thioguanine (6TG) levels in erythrocytes
Time frame: Up to week 25
The fraction of patients with 6TG levels over 200 nmol/mmol Hb at week 13 and 25 (ie after 12 weeks standard and allopurinol treatment respectively)
13 secondary outcomes
Mean level of 6-thioguanine
Time frame: Up to week 25
Mean level of DNA-incorporated thioguanine (DNA-TGN)
Time frame: Up to week 25
Mean level of 6-methylmercaptopurine (6MMP)
Time frame: Up to week 25
Mean levels of platelets
Time frame: Up to week 25
Mean levels of hemoglobin
Time frame: Up to week 25
Mean levels of absolute neutrophil count (ANC)
Time frame: Up to week 25
Mean levels of white blood cells (WBC)
Time frame: Up to week 25
Glutamate pyruvate transaminase (GPT)
Time frame: Up to week 25
Bilirubin
Time frame: Up to week 25
Hypoglycemia
Time frame: Up to week 25
Metabolic disturbance
Time frame: Up to week 25
Incidence of serious adverse events (SAE)
Time frame: Up to week 29
Cumulative dose of 6-mercaptopurine and methotrexate
Time frame: Up to week 29
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2017.
- 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.
Jonas Abrahamsson, PhD, MD study chair
Childrens Cancer Center, Queen Silvia Children Hospital, Sahlgrenska Academy, Gothenburg, Sweden
Riita Niinimäki, PhD, MD principal investigator
Dept of Pediatrics and Adolescents, Oulu University Hospital, Box 23, 90029 OYS, Finland
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 Allopurinol and Standard treatment in people with Lymphoblastic Leukemia, Acute, Childhood, run by Vastra Gotaland Region 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 5 inclusion and 8 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 16 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 Sweden, Finland. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jonas Abrahamsson, PhD, MD (+46 707 695159, vobjab@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6-thioguanine (6TG) levels in erythrocytes (time frame: Up to week 25). 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 16 Jan 2017.