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

NCT ID: NCT03022747

Last Updated: 2017-01-16

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2019-04-30

Brief 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. 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.

Conditions

Lymphoblastic Leukemia, Acute, Childhood

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard maintenance therapy

Standard maintenance therapy with 6 mercaptopurine and methotrexate

Group Type: ACTIVE_COMPARATOR

Standard treatment

Intervention Type: DRUG

Oral 6-mercaptopurine and methotrexate

Allopurinol treatment

The second 12 week phase during which allopurinol is added to oral 6-mercaptopurine and methotrexate therapy

Group Type: EXPERIMENTAL

Allopurinol

Intervention Type: DRUG

Allopurinol is added to standard oral 6-mercaptopurine and methotrexate

Interventions

Allopurinol

Allopurinol is added to standard oral 6-mercaptopurine and methotrexate

Intervention Type: DRUG

Standard treatment

Oral 6-mercaptopurine and methotrexate

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vastra Gotaland Region

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonas Abrahamsson, PhD, MD

Role: STUDY_CHAIR

Childrens Cancer Center, Queen Silvia Children Hospital, Sahlgrenska Academy, Gothenburg, Sweden

Riita Niinimäki, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Dept of Pediatrics and Adolescents, Oulu University Hospital, Box 23, 90029 OYS, Finland

Locations

Dept of Pediatrics and Adolescents, Oulu University Hospital, Box 23, 90029 OYS, Finland

Oulu, , Finland

Site Status: NOT_YET_RECRUITING

Childrens' Cancer Centre, Queen Silvias Childrens and Adolescents Hospital

Gothenburg, , Sweden

Site Status: RECRUITING

Linköping University Hospital, Dept of Pediatrics

Linköping, , Sweden

Site Status: NOT_YET_RECRUITING

Countries

Finland; Sweden

Central Contacts

Jonas Abrahamsson, PhD, MD

Role: CONTACT

vobjab@gmail.com

+46 707 695159

Torben Ek, PhD, MD

Role: CONTACT

torben.ek@mac.com

+46 706 169284

Facility Contacts

Riita Niinimäki, MD, PhD

Role: primary

riita.niinimaki@ppshp.fi

+358 8 3155832

Lene Karlsson, MD

Role: primary

lene.karlsson@vgregion.se

+46 313435610

Hartmut Vogt, MD, PhD

Role: primary

hartmut.vogt@regionostergotland.se

+46 101031343

Other Identifiers

Allopurinol Study V3.0

Identifier Type: -

Identifier Source: org_study_id