NOPHO ALL-2008 Pilot Study on Consolidation Therapy for Children and Adolescents With Acute Lymphoblastic Leukemia
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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Individual 6-mercaptopurine(6MP) Dose Increments in Children With Acute Lymphoblastic Leukemia (ALL) Receiving High-dose Methotrexate (HDM) and PEG-asparaginase|
- Toxicity of Treatment in Terms of Number of Participants With Serious Adverse Events or Adverse Events, Reported [ Time Frame: 3 months ( 79 days ) ] [ Designated as safety issue: Yes ]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.
- Incorporation of 6-thioguanine Nucleotides (6TGN) Into Leukocyte DNA, Development of Asparaginase Antibody Production [ Time Frame: During the 3 months consolidation therapy ] [ Designated as safety issue: No ]Biweekly bloodsamples during the 3 months are analyzed for 6TGN incorporation into leucocyte DNA. In addition Methylated Mercaptopurin (MeMP) and Erythrocyte-Methotrexate level is measured
|Study Start Date:||December 2007|
|Study Completion Date:||May 2009|
|Primary Completion Date:||January 2009 (Final data collection date for primary outcome measure)|
Experimental: 6 mercaptopurine arm
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
Standard dose 25 mg/m^2/day. Can be increased up to 75 mg/m^2/day if the myelosuppression is acceptable (ANC>0.5 T-count >50)
Other Name: PURINETHOL
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.
|Department of Pediatrics, Rigshospitalet|
|Department of Pediatrics, University Hospital|
|Department of Pediatrics, Drottning Sylvias Pediatric Hospital|
|Study Chair:||Kjeld Schmiegelow, M.D.||Pediatric Clinic II, RIgshospitalet, Copenhagen, DK-2100|