Liposomal Cytarabine for Central Nervous System (CNS)-Treatment in High-risk Acute Lymphoblastic Leukemia (ALL)

Study Overview
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Brief Summary
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Replacement of intrathecal Triple (methotrexate, cytarabine, prednisolone) with intrathecal liposomal cytarabine and prednisolone during maintenance therapy will decrease the CNS relapse rate in high-risk ALL patients. Both acute and long-term toxicity are equal in both treatment arms.

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 replace intrathecal triple (methotrexate, cytarabine and glucocorticosteroid) by intrathecal liposomal cytarabine and glucocorticosteroid during maintenance therapy in order to decrease the central nervous system relapse rate in high-risk acute lymphoblastic leukemia patients. To evaluate acute and long-term toxicity in both treatment arms.

Official Title
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Phase III Randomised Study on Liposomal Cytarabine (DepoCyte®) vs. Intrathecal Triple for CNS-Treatment During Maintenance Therapy in High-Risk Acute Lymphoblastic Leukemia Patients in NOPHO ALL 2008 Treatment Protocol

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: Liposomal cytarabine
* Drug: Intrathecal triple


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: High risk acute lymphoblastic leukemia Not eligible for bone marrow transplantation Age 1-18 Written informed consent has been obtained Exclusion Criteria: Persistent NCI grade 3-4 neurotoxicity from previous treatments Bilineage ALL Leukemia predisposing syndromes (e.g. Downs syndrome, Ataxia Telangiectasia) Previous cancer Known intolerance to NOPHO ALL 2008 anticancer agents Sexually active females will use safe contraceptives Previous treatment with intrathecal liposomal cytarabine

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liposomal cytarabine<br>Intrathecal liposomal cytarabine (25 - 50 mg) combined with intrathecal prednisolone sodium succinate and oral dexamethasone 6 times during maintenance treatment for high-risk ALL | Drug: Liposomal cytarabine<br>* Intrathecal liposomal cytarabine combined with intrathecal prednisolone and oral dexamethasone during maintenance treatment for high-risk ALL<br>* Other names: Di-Adreson F;|
| Active Comparator: Intrathecal triple<br>Intrathecal methotrexate, cytarabine and prednisolone | Drug: Intrathecal triple<br>* Intrathecal methotrexate (8-12 mg), cytarabine (20 - 30 mg) and prednisolone sodium succinate (12,5 - 20 mg) 6 times during maintenance treatment in high-risk ALL protocol<br>* Other names: Cytosine arabinoside;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of leukemia relapses in the central nervous system |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurological toxicity |  | 6 months after cessation of leukemia therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukemia, Central nervous system, Neurotoxicity, Liposomal cytarabine, Children, Acute lymphoblastic leukemia, Childhood acute lymphoblastic leukemia, Intrathecal, Efficacy, Safety