Optimizing 6-mercaptopurine Therapy in Pediatric Acute Lymphoblastic Leukemia by Using Allopurinol

January 11, 2017 updated by: Vastra Gotaland Region

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Jonas Abrahamsson, PhD, MD
  • Phone Number: +46 707 695159
  • Email: vobjab@gmail.com

Study Contact Backup

Study Locations

  • Finland
      • Oulu, Finland, 90029 OYS
        • Not yet recruiting
        • Dept of Pediatrics and Adolescents, Oulu University Hospital, Box 23, 90029 OYS, Finland
        • Contact:
  • Sweden
      • Gothenburg, Sweden, 416 85
        • Recruiting
        • Childrens' Cancer Centre, Queen Silvias Childrens and Adolescents Hospital
        • Contact:
      • Linköping, Sweden, 58185
        • Not yet recruiting
        • Linköping University Hospital, Dept of Pediatrics
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

2 years to 15 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Standard maintenance therapy
Standard maintenance therapy with 6 mercaptopurine and methotrexate
Drug: Standard treatment
Oral 6-mercaptopurine and methotrexate
Experimental: Allopurinol treatment
The second 12 week phase during which allopurinol is added to oral 6-mercaptopurine and methotrexate therapy
Drug: Allopurinol
Allopurinol is added to standard oral 6-mercaptopurine and methotrexate

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
Up to week 25

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mean level of 6-thioguanine
Time Frame: Up to week 25
The mean level of 6TG at week 13 and 25
Up to week 25
Mean level of DNA-incorporated thioguanine (DNA-TGN)
Time Frame: Up to week 25
The mean level of DNA-TGN at week 13 and 25
Up to week 25
Mean level of 6-methylmercaptopurine (6MMP)
Time Frame: Up to week 25
The mean level of 6MMP at week 13 and 25
Up to week 25
Mean levels of platelets
Time Frame: Up to week 25
Comparison of weighted mean of platelets in the treatment phases
Up to week 25
Mean levels of hemoglobin
Time Frame: Up to week 25
Comparison of weighted mean of hemoglobin in the treatment phases
Up to week 25
Mean levels of absolute neutrophil count (ANC)
Time Frame: Up to week 25
Comparison of weighted mean of ANC in the treatment phases
Up to week 25
Mean levels of white blood cells (WBC)
Time Frame: Up to week 25
Comparison of weighted mean of WBC in the treatment phases
Up to week 25
Glutamate pyruvate transaminase (GPT)
Time Frame: Up to week 25
Comparison of weighted means of serum GPT in the treatment phases
Up to week 25
Bilirubin
Time Frame: Up to week 25
Comparison of weighted means of serum bilirubin in the treatment phases
Up to week 25
Hypoglycemia
Time Frame: Up to week 25
Comparison of incidence of hypoglycemia and laboratory measures of metabolic disturbance during the treatment phases
Up to week 25
Metabolic disturbance
Time Frame: Up to week 25
Comparison of incidence of laboratory measures of metabolic disturbance during the treatment phases
Up to week 25
Incidence of serious adverse events (SAE)
Time Frame: Up to week 29
Comparison of the frequency of SAE in the treatment phases
Up to week 29
Cumulative dose of 6-mercaptopurine and methotrexate
Time Frame: Up to week 29
Comparison of the cumulative dose of 6MP and methotrexate and days with treatment interruption in the two treatment arms
Up to week 29

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Vastra Gotaland Region

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Jonas Abrahamsson, PhD, MD, Childrens Cancer Center, Queen Silvia Children Hospital, Sahlgrenska Academy, Gothenburg, Sweden
  • Principal Investigator: Riita Niinimäki, PhD, MD, Dept of Pediatrics and Adolescents, Oulu University Hospital, Box 23, 90029 OYS, Finland

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2017

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2018

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 9, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 11, 2017

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 16, 2017

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 16, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 11, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Allopurinol Study V3.0

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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