ALL2008 Protocol for Childhood Acute Lymphoblastic Leukemia (ALL) - 6MP Consolidation Therapy

Study Overview
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Brief Summary
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The purpose of this study is to increase the fraction of patients, who become MRD-negative during consolidation for the non-HR ALL group through individualized intensification of the 6MP-dosage days 30-85.

Detailed Description
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20% of children with ALL still fails to be cured. The ALL-2008 protocol is a treatment and research protocol that aims to improve the overall outcome of Nordic children and adolescents with ALL in comparison with the ALL-2000 protocol and previous NOPHO protocols. The specific and primary objectives of the randomised study is: To increase the fraction of patients, who become MRD-negative during consolidation for the non-HR ALL group through individualised intensification of the 6MP-dosage days 30-85. We will additionally measure EFS and toxicity as secondary end points of effect.

Official Title
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Nordic Society of Paediatric Haematology and Oncology Treatment Protocol for Children (1.0 - 17.9 Years of Age) and Young Adults (18-45 Years of Age) With ALL. Efficacy of Individualised 6MP Dosing During Consolidation Therapy

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: 6MPindividualized
* Drug: 6MPfixed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Childhood ALL All mandatory biological data are available6 Written informed consent has been obtained Exclusion Criteria: Mixed lineage ALL Pre-treatment with glucocorticosteroids or other antileukemic agents for more than 1 week ALL predisposition syndromes Previous cancer Off protocol administration of additional chemotherapy during induction therapy Sexually active females not using contraception TPMT-deficiency

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 45 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 6MPfixed<br>Fixed dose 6-mercaptopurine days 30-85 | Drug: 6MPfixed<br>* Oral 6-mercaptopurine at a fixed dose of 25 mg/m2 treatment days 30-85<br>* Other names: PuriNethol, Puri-Nethol (6-mercaptopurine);|
| Experimental: 6MPindividualized<br>Individualized dose increments of 6-mercaptopurine days 30-85 | Drug: 6MPindividualized<br>* Oral 6-mercaptopurine with a starting dose of 25 mg/m2 and upward adjusted in steps of 25 mg/m2 (i.e. 50 or 75 mg/m2) if unacceptable bone-marrox toxicity is not encountered<br>* Other names: PuriNethol, Puri-Nethol (6-mercaptopurine);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fraction of patients that become MRD-negative at treatment days 85 and/or 92 (end-of-consolidation) and event-free survival. MRD is measured either by Flow-cytometry (for PreB-ALL patients) or PCR for clonal generearrangements(for T-ALL patients) |  | 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity of treatment, degree of myelo-, hepato- and renal toxicity; and development of asparaginase antibodies. |  | 6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute lymphoblastic leukemia, child, 6-mercaptopurine, minimal residual disease, efficacy, childhood acute lymphoblastic leukemia