Clinical trial NCT01593488: Liposomal Cytarabine in the Treatment of Central Nervous System Resistant or Relapsed Acute Lymphoblastic Leukemia in Children
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia
Keywords: recurrent
CNS disease
intrathecal therapy
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
Collaborators: name: Santobono-Pausilpon Hospital
name: IRCCS Azienda Ospedaliero-Universitaria di Bologna
name: University of Bologna
First posted: 2012-05-08
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: number of cerebrospinal fluid (CSF) responses
timeFrame: 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
measure: number of patients with grade 3 or higher neurological adverse events, excluding headache) according to CTCAE 4.02
timeFrame: assessed from date of patient registration to date of cerebrospinal fluid response, up to 12 weeks
Secondary outcomes:
measure: time to reaching CSF response
timeFrame: date of patient registration to date of CSF response, up to 12 weeks
measure: duration of CSF response
timeFrame: up to 12 months
measure: worst grade non neurologic Adverse event during induction, according to CTCAE 4.02
timeFrame: up to 12 weeks
measure: worst grade toxicity after induction therapy according to CTCAE 4.02
timeFrame: up to 12 months
measure: overall survival
timeFrame: one year
measure: time from patient registration to progression of disease in non CNS site
timeFrame: up to one year
measure: concentration of study drug present in CSF at each induction therapy
timeFrame: prior to each induction therapy at 15 day intervals for up to 6 cycles
measure: correlation of activity and toxicity with residual study drug level in CSF during induction
timeFrame: measured at 15 day intervals for up to 6 cycles
Other outcomes:
Locations:
city: Catania
country: Italy
facility: P.O. Gaspare Rodolico
city: Genova
country: Italy
facility: Istituto G. Gasilini
city: Monza
country: Italy
facility: Ospedale S. Gerardo Clinica Pediatrica
city: Napoli
country: Italy
facility: AORN Santobon - Pauslipon
city: Padova
country: Italy
facility: A.O. Università Padova
city: Palermo
country: Italy
facility: ARNAS Osp Civico di Cristina
city: Roma
country: Italy
facility: IRCCS Ospedale Bambino Gesu'
city: San Giovanni Rotondo
country: Italy
facility: Casa Sollievo della Sofferenza
city: Trieste
country: Italy
facility: IRCCS Burlo Garofalo Istituto per l'Infanzia Emato Oncologia
city: Verona
country: Italy
facility: Ospedale Policlinico G.B. Rossi
Study officials:
affiliation: Santobono-Pausilipon Hospital
name: Rosanna Parasole, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute, Naples
name: Massimo Di Maio, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute, Naples
name: Francesco Perrone, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Policlinico S. Orsola-Malpighi, Bologna
name: A. Pession
role: PRINCIPAL_INVESTIGATOR
affiliation: Policlinico S. Orsola-Malpighi, Bologna
name: William Morello
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Bologna
name: E. Strocchi
role: PRINCIPAL_INVESTIGATOR
References: