Study of 6-Thioguanine in Combination With 6-Mercaptopurine During Maintenance Therapy of Childhood Lymphoma
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|ClinicalTrials.gov Identifier: NCT02141100|
Recruitment Status : Withdrawn
First Posted : May 19, 2014
Last Update Posted : October 7, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|Non-Hodgkin Lymphoma||Drug: 6-thioguanine||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||July 2014|
|Estimated Primary Completion Date :||October 2016|
|Estimated Study Completion Date :||October 2016|
Experimental: 6-thioguanine, 6-mercaptopurine and methotrexate
This is the only treatment arm; all eligible patients will receive standard methotrexate/6-mercaptopurine (6MP/MTX) maintenance therapy supplemented with 6-thioguanine (6TG).
Patients are enrolled when they have 12 to 3.5 months remaining of their maintenance therapy. After dose reduction in 6MP to 2/3 of the current dose 6TG therapy is initiated with a starting dose of 2.5 mg/m2/day. The 6TG dose will hereafter be increased at 2.5 mg/m2/day every 14 days until a max. of 12.5 mg/m2/day is reached or until the thiopurine metabolite profile (Ery-TGN/Ery-MeMP) has been increased by at least a factor 5.
All eligible patients will be supplemented with 6-thioguanine in addition to the standard therapy with 6-mercaptopurine and methotrexate.
In case of significant myelo-/hepatotoxicity all therapy will be paused. If patients develop VOD they will be excluded from further 6TG therapy.
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02141100
|Dept. of Pediatric Oncology, JMC, Rigshospitalet|
|Copenhagen, Denmark, 2100|
|Study Chair:||Kjeld Schmiegelow, M.D.||Rigshospitalet, Denmark|