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

This study has suspended participant recruitment.
(Depocyte recalled by the Italian Medicine Agency after EMA report lack of adequate sterility assurance by manufacturer Temporary suspension)
Sponsor:
Collaborators:
Santobono-Pausilpon Hospital
Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
University of Bologna
Information provided by (Responsible Party):
National Cancer Institute, Naples
ClinicalTrials.gov Identifier:
NCT01593488
First received: April 27, 2012
Last updated: August 29, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Acute Lymphoblastic Leukemia
Drug: liposomal cytarabine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute, Naples:

Primary Outcome Measures:
  • number of cerebrospinal fluid (CSF) responses [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • number of patients with grade 3 or higher neurological adverse events, excluding headache) according to CTCAE 4.02 [ Time Frame: assessed from date of patient registration to date of cerebrospinal fluid response, up to 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • time to reaching CSF response [ Time Frame: date of patient registration to date of CSF response, up to 12 weeks ] [ Designated as safety issue: No ]
    date of reaching CSF response is the first date of two consecutive negative cytomorphologic exams of CSF

  • duration of CSF response [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]
    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

  • worst grade non neurologic Adverse event during induction, according to CTCAE 4.02 [ Time Frame: up to 12 weeks ] [ Designated as safety issue: No ]
  • worst grade toxicity after induction therapy according to CTCAE 4.02 [ Time Frame: up to 12 months ] [ Designated as safety issue: No ]
    Measured from date of CSF response

  • overall survival [ Time Frame: one year ] [ Designated as safety issue: No ]
  • time from patient registration to progression of disease in non CNS site [ Time Frame: up to one year ] [ Designated as safety issue: No ]
  • concentration of study drug present in CSF at each induction therapy [ Time Frame: prior to each induction therapy at 15 day intervals for up to 6 cycles ] [ Designated as safety issue: No ]
  • correlation of activity and toxicity with residual study drug level in CSF during induction [ Time Frame: measured at 15 day intervals for up to 6 cycles ] [ Designated as safety issue: No ]

Estimated Enrollment: 31
Study Start Date: March 2012
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intrathecal liposomal cytarabine Drug: liposomal cytarabine
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)

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01593488

Locations
Italy
AORN Santobon - Pauslipon
Napoli, Italy
IRCCS Ospedale Bambino Gesu'
Roma, Italy
IRCCS Burlo Garofalo Istituto per l'Infanzia Emato Oncologia
Trieste, Italy
Sponsors and Collaborators
National Cancer Institute, Naples
Santobono-Pausilpon Hospital
Azienda Ospedaliera Universitaria di Bologna Policlinico S. Orsola Malpighi
University of Bologna
Investigators
Principal Investigator: Rosanna Parasole, M.D. Santobono - Pausilipon Hospital
Principal Investigator: Massimo Di Maio, M.D. National Cancer Institute, Naples
Principal Investigator: Francesco Perrone, M.D., Ph.D. National Cancer Institute, Naples
Principal Investigator: A. Pession Policlinico S. Orsola-Malpighi, Bologna
Principal Investigator: William Morello Policlinico S. Orsola-Malpighi, Bologna
Principal Investigator: E. Strocchi University of Bologna
  More Information

No publications provided

Responsible Party: National Cancer Institute, Naples
ClinicalTrials.gov Identifier: NCT01593488     History of Changes
Other Study ID Numbers: CILI, 2011-002622-48
Study First Received: April 27, 2012
Last Updated: August 29, 2012
Health Authority: Italy: Ethics Committee

Keywords provided by National Cancer Institute, Naples:
recurrent
CNS disease
intrathecal therapy

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 20, 2014