Liposomal Cytarabine in the Treatment of Central Nervous System Resistant or Relapsed Acute Lymphoblastic Leukemia in Children

Study Overview
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Brief Summary
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The purpose of this study is to describe the activity and toxicity of a new formulation of cytarabine called liposomal cytarabine given into the central nervous system for the treatment of central nervous system localization of acute lymphoblastic leukemia (ALL) in children and adolescents.

Detailed Description
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Liposomal cytarabine (DepoCyte) is a new formulation of the drug cytarabine, a drug commonly used in the treatment of ALL. This formulation of the drug can be given intrathecally (into the spinal fluid), and is released slowly over a longer period, about two weeks. This allows a longer exposure of the drug to the central nervous system, and requires fewer intrathecal injections for the patient.

Official Title
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Multicentered Phase II Study Evaluating the Activity and Toxicity of Liposomal Cytarabine in the Treatment of Children and Adolescents With Acute Lymphoblastic Leukemia With Resistent or Relapsed Central Nervous System Involvement

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: liposomal cytarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age < 18 years Diagnosis of acute lymphoblastic leukemia (ALL) Central nervous system involvement with malignant cells present in cerebrospinal fluid CNS involvement may be refractive to prior systemic therapy, a first recurrence after prior systemic and intrathecal therapy or a second recurrence CNS involvement may be an isolated lesion or present with other sites of disease ECOG performance status 0-2 Life expectancy of at least 8 weeks Absence of severe organ dysfunction Informed consent Exclusion Criteria: Eligibility for AIEOP studies of first recurrence of ALL,and receiving therapy in a center participating in the AIEOP studies Concurrent treatment with experimental therapies Severe neurologic toxicities from previous chemotherapy Severe coagulopathy at time of recurrence Sepsis Intrathecal therapy within 1 week of planned study therapy Total body or head and spine radiation within 8 weeks of enrolment Bone marrow transplant within 8 weeks of start of study therapy.

Ages Eligible for Study
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Minimum 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: Intrathecal liposomal cytarabine<br> | Drug: liposomal cytarabine<br>* given intrathecally in induction phase every 15 days until CSF response for up to 7 injections. Then it is given every 4 weeks during consolidation phase while patient awaiting bone marrow transplant. For those patients who are not candidates for a bone marrow transplant, the drug will be given every 3 months for 4 administrations (maintenance therapy)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of cerebrospinal fluid (CSF) responses |  | from two weeks after date of patient registration until the date of second consecutive cerebrospinal fluid exam that is negative for malignant cells, up to 12 weeks | 
| number of patients with grade 3 or higher neurological adverse events, excluding headache) according to CTCAE 4.02 |  | assessed from date of patient registration to date of cerebrospinal fluid response, up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to reaching CSF response | date of reaching CSF response is the first date of two consecutive negative cytomorphologic exams of CSF | date of patient registration to date of CSF response, up to 12 weeks | 
| duration of CSF response | duration of response is the length of time in days from the date of the CSF response to the date of the first positive cytomorphologic CSF exam | up to 12 months | 
| worst grade non neurologic Adverse event during induction, according to CTCAE 4.02 |  | up to 12 weeks | 
| worst grade toxicity after induction therapy according to CTCAE 4.02 | Measured from date of CSF response | up to 12 months | 
| overall survival |  | one year | 
| time from patient registration to progression of disease in non CNS site |  | up to one year | 
| concentration of study drug present in CSF at each induction therapy |  | prior to each induction therapy at 15 day intervals for up to 6 cycles | 
| correlation of activity and toxicity with residual study drug level in CSF during induction |  | measured at 15 day intervals for up to 6 cycles | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CNS disease, intrathecal therapy, recurrent