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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Leukemia, Lymphocytic, Acute

Intervention / Treatment
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* Drug: 6-mercaptopurine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: B-lineage ALL 1-17.9 years WBC <100, clinical remission obtained day 2 Written consent to participation. Exclusion Criteria: t(9;22) Hypodiploidy 11q23-aberrations TPMT-deficiency Intolerance to MTX or 6MP

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 6 mercaptopurine arm<br>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 | Drug: 6-mercaptopurine<br>* 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)<br>* Other names: PURINETHOL;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity of Treatment in Terms of Number of Participants With Serious Adverse Events or Adverse Events, Reported | 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. | 3 months ( 79 days ) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incorporation of 6-thioguanine Nucleotides (6TGN) Into Leukocyte DNA, Development of Asparaginase Antibody Production | 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 | During the 3 months consolidation therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukemia, Lymphocytic, Acute [C04.557.337.428.511], 6-mercaptopurine, methotrexate, asparaginase