Clinical Trial: Study of 6-Thioguanine in Combination With 6-Mercaptopurine During Maintenance Therapy of Childhood Lymphoma

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official Title: A Phase 1-2 Study of 6-Thioguanine in Combination With Methotrexate and 6-Mercaptopurine During Maintenance Therapy of Childhood Non-Hodgkin's Lymphoma

Brief Summary:

The purpose of this phase 1-2 study is to explore the applicability of supplementing standard methotrexate/6-mercaptopurine (MTX/6MP) maintenance therapy of children with non-Hodgkin lymphoma with 6-thioguanine (6TG).

The investigators hypothesize that addition of 6TG to 6MP-based maintenance therapy of patients with high TPMT activity will mimic the more favourable thiopurine metabolism of patients with low TPMT activity and ultimately reduce relapse rates.


Detailed Summary: MTX/6MP maintenance therapy is challenged by treatment related liver toxicity, failure to achieve the target treatment parameter in all patients, and lack of direct parameters for monitoring treatment efficacy or even intensity. Patients with low activity of thiopurine methyltransferase (TPMT), an enzyme involved in the metabolism of 6MP, have lower levels of liver toxic metabolites (MeMPs), higher levels of the major active metabolites (TGNs), and reduced relapse rates. Most patients (90%) have high TPMT activity. Nearly all patients with high TPMT activity and high MeMP levels experience elevated liver enzymes. Increasing the 6MP dose in patients with high TPMT activity, to intensify therapy, will mainly lead to further increase in the MeMP level. A novel approach compensating the adverse thiopurine metabolism of the majority of patients is warranted.
Sponsor: Kjeld Schmiegelow

Current Primary Outcome: Change in median thiopurine metabolite index [ Time Frame: Every 2 weeks up to the max. trial period of 12 months ]

Change in Ery-TGN/Ery-MeMP after addition of 6-thioguanine to therapy. The thiopurine metabolites will be measured every 2 weeks during the trial period. The trial period is max. 12 months.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Toxicities [ Time Frame: Minimum every 2 weeks, up to 12 months ]
    Myelo- and hepatotoxicity. Blood samples (WBC, neutrophil count, thrombocyte count, ALAT, bilirubin, factors 2-7-10) will be taken every 2 weeks throughout the trial period and at additional time points in case of clinical signs/symptoms of toxicity.
  • Change in median DNA-TG [ Time Frame: Every 2 weeks, up to 12 months ]
    Change in DNA-TG (incorporation of thioguanine nucleotides in to DNA) after addition of 6-thioguanine. This parameter will be measured every 2 weeks during the trial period. The max. trial period is 12 months.


Original Secondary Outcome: Same as current

Information By: Rigshospitalet, Denmark

Dates:
Date Received: May 7, 2014
Date Started: July 2014
Date Completion: October 2016
Last Updated: October 6, 2016
Last Verified: October 2016