NOPHO ALL-2008 Pilot Study on Consolidation Therapy for Children and Adolescents With Acute Lymphoblastic Leukemia

Phase 2

Completed

Brief Summary: The present pharmacokinetic (PK)-pharmacodynamic (PD) study will explore the toxicity and antileukemic response during the initial 3 months of individualised therapy of children and young adults with acute lymphoblastic leukemia (ALL). The investigators will on an individual toxicity-titrated basis attempt to increase the dose intensity of the 6-mercaptopurine used in the two-months post-remission treatment phase of lower risk childhood ALL. This will be performed together with continuous PEG-ASP (every 2nd week) and interspersed HD-MTX (5 g/m\^2) every 3rd week. Thus, the trial will also test the feasibility of this particular drug combination.

Detailed Description: In addition to the details above we will also explore

* the relationship of the post-HD-MTX MRD-levels with the dose of 6MP, TPMT-activity, DNA-6TGN, E-6TGN, E-MeMP, E-MTX, and presence of ASP-antibodies,

* the early development of anti-ASP antibodies during continuous PEG-ASP therapy.

The study could improve the understanding of the pharmacodynamics of the 6MP/HD-MTX interaction in combination with PEG-ASP.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Arm && Interventions

Group	Intervention	Description
6 mercaptopurine arm	6-mercaptopurine	All patients received basic daily 6MP (6-mercaptopurine) (25 mg/m\^2) and in addition high-dose methotrexate(HDM) every 3rd week (3 times HDM in total) and PEG-asparaginase every 14th day. Patients increased the dose of 6MP 2 weeks after each HDM if if the myelotoxicity had been acceptable. This means 2 increments since the study stopped 2 weeks after the last HDM

Primary Outcome Measures

Name	Time	Method
Toxicity of Treatment in Terms of Number of Participants With Serious Adverse Events or Adverse Events, Reported	3 months ( 79 days )	Number of participants following the protocol treatment for the full consolidation therapy with toxicity in this pilot study trying to individually titrate 6-mercaptopurine to the highest tolerable level during Consolidation.

Secondary Outcome Measures

Name	Time	Method
Incorporation of 6-thioguanine Nucleotides (6TGN) Into Leukocyte DNA, Development of Asparaginase Antibody Production	During the 3 months consolidation therapy	Biweekly bloodsamples during the 3 months are analyzed for 6TGN incorporation into leucocyte DNA. In addition Methylated Mercaptopurine (MeMP) and Erythrocyte-Methotrexate level is measured

Locations (3): Department of Pediatrics, Rigshospitalet
🇩🇰
Copenhagen, Denmark
Department of Pediatrics, University Hospital
🇩🇰
Odense, Denmark
Department of Pediatrics, Drottning Sylvias Pediatric Hospital
🇸🇪
Gothenburg, Sweden