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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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 L

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 Summary: 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.
Sponsor: Vastra Gotaland Region

Current 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)


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Mean level of 6-thioguanine [ Time Frame: Up to week 25 ]
    The mean level of 6TG at week 13 and 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
  • Mean level of 6-methylmercaptopurine (6MMP) [ Time Frame: Up to week 25 ]
    The mean level of 6MMP at week 13 and 25
  • Mean levels of platelets [ Time Frame: Up to week 25 ]
    Comparison of weighted mean of platelets in the treatment phases
  • Mean levels of hemoglobin [ Time Frame: Up to week 25 ]
    Comparison of weighted mean of hemoglobin in the treatment phases
  • Mean levels of absolute neutrophil count (ANC) [ Time Frame: Up to week 25 ]
    Comparison of weighted mean of ANC in the treatment phases
  • Mean levels of white blood cells (WBC) [ Time Frame: Up to week 25 ]
    Comparison of weighted mean of WBC in the treatment phases
  • Glutamate pyruvate transaminase (GPT) [ Time Frame: Up to week 25 ]
    Comparison of weighted means of serum GPT in the treatment phases
  • Bilirubin [ Time Frame: Up to week 25 ]
    Comparison of weighted means of serum bilirubin in the treatment phases
  • Hypoglycemia [ Time Frame: Up to week 25 ]
    Comparison of incidence of hypoglycemia and laboratory measures of metabolic disturbance during the treatment phases
  • Metabolic disturbance [ Time Frame: Up to week 25 ]
    Comparison of incidence of laboratory measures of metabolic disturbance during the treatment phases
  • Incidence of serious adverse events (SAE) [ Time Frame: Up to week 29 ]
    Comparison of the frequency of SAE in the treatment phases
  • 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


Original Secondary Outcome: Same as current

Information By: Vastra Gotaland Region

Dates:
Date Received: January 9, 2017
Date Started: January 2017
Date Completion: April 2019
Last Updated: January 11, 2017
Last Verified: January 2017