Central Nervous System (CNS) Involvement in Acute Myeloid Leukemia (AML) (AML1617)

October 24, 2022 updated by: Gruppo Italiano Malattie EMatologiche dell'Adulto

Central Nervous System (CNS) Involvement in Acute Myeloid Leukemia (AML): an Observational Retrospective Multicentre Study on Patients Previously Registered in GIMEMA Clinical Trials

The present study aims at evaluating the prognostic factors at diagnosis predicting Central Nervous System (CNS) relapse in order to identify a group of patients with higher risk of CNS involvement in which prophylaxis with liposomal Ara-C or other drugs should be indicated.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

CNS involvement in AML is a rare event, poorly detailed in literature. Few data are available in pediatric cases, and less frequent in adult cases. Predisposing factors for AML adult patients with CNS involvement include young age, higher level of lactate dehydrogenase and white blood cells (WBC) counts at diagnosis, FAB M4 and M5 morphology, chromosome 16 inversion and chromosome 11 abnormality. No consensus exists regarding the treatment of AML patients with CNS involvement. Protocols used for AML treatment are largely based on high doses of cytarabine, which penetrate the blood brain barrier. On the contrary of acute lymphoid leukemia (ALL), prophylaxis with intrathecal chemotherapy is not routinely used in AML. Roudoski et al. showed that, when lumbar puncture (LP) was performed in 1,370 patients, only if clinically indicated, CNS disease was detected in 45 (3.3%) patients. Another 42 patients underwent routine LP as part of an investigational protocol, and in 8 (19%) CNS disease was detected (P<0.0001). Risk factors included high LDH, African-American ethnicity, and young age. Patients receiving high-dose cytarabine and those that did not had similar rates of CNS involvement. Disease free survival (DFS) and overall survival were shorter in patients with CNS involvement. Treatment in case of CNS involvement is not well established; the potential acute and long-term complications associated with cranial irradiation often limit its use. Prognosis remains poor also with high doses of cytarabine and/or therapeutic intrathecal chemotherapy. Castagnola et al. reported showed the outcome of 9 patients woth CNS+ AML: NSL was treated as follows: 4 patients received combined systemic HD Ara-C, cranial radiation therapy and intrathecal (IT) methotrexate (MTX); a second group of 4 patients was treated with HD Ara-C, IT MTX without cranial irradiation; HD Ara-C alone was administered in one patient. All patients of the first group and 2 patients of the second who achieved a complete remission (CR) had a median survival of 10 months after CNS involvement, while for the non-remitters it was 2 months. The unique durable response was observed after allogeneic bone marrow transplantation. Sanders et al. reported that craniospinal irradiation with or without intrathecal chemotherapy appears to be effective at eliminating leukemia in the craniospinal axis. However, the eradication of disease in the CNS was not found to be effective at preventing disease recurrence in the bone marrow, and despite improved control of disease in the CNS, adult patients with a CNS recurrence still had a poor prognosis. Furthermore, the rapidly fatal course of disease prevented an assessment of the durability of CNS response to irradiation. Aoki et al reported that allogeneic haematopoietic stem cell transplantation (HSCT) might improve outcomes for CNS+AML and Bar et al, showed that presence of CNS pre-HCT had no independent influence on post transplant outcome, which was primarily influenced by status of systemic disease at time of HCT. Due to the rarity of the disease we want to collect the data about CNS involvement, either at diagnosis or along the course of the disease, in AML patients already registered in previous GIMEMA Studies, trying to identify incidence, prognosis, prognostic factors and the best adequate treatment.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
21

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Alessandria, Italy
        • Aon Ss. Antonio E Biagio E C. Arrigo - Alessandria - Soc Ematologia
      • Ancona, Italy
        • Aou Ospedali Riuniti "Umberto I - G.M. Lancisi - G. Salesi"- Ancona - Sod Clinica Ematologica
      • Bari, Italy
        • Aou Consorziale Policlinico - Bari - Uo Ematologia Con Trapianto
      • Cagliari, Italy
        • Ao Brotzu, Presidio Ospedaliero A. Businco - Cagliari - Sc Ematologia E Ctmo
      • Milano, Italy
        • Fondazione Irccs Ca' Granda, Ospedale Maggiore Policlinico - Milano - Ematologia - Padiglione Marcora
      • Napoli, Italy
        • Aou Federico Ii - Napoli - Uoc Ematologia
      • Novara, Italy
        • Aou Maggiore Della Carita' Di Novara - Scdu Ematologia
      • Perugia, Italy
        • Ao Di Perugia, Ospedale S. Maria Della Misericordia - Ematologia E Trapianto Midollo Osseo
      • Piacenza, Italy
        • Asl Di Piacenza, Ospedale "Guglielmo Da Saliceto" - Ematologia E Centro Trapianti
      • Roma, Italy
        • Fondazione Policlinico Universitario Agostino Gemelli Irccs - Roma - Area Ematologica
      • Roma, Italy
        • Aou Policlinico Tor Vergata - Roma - Uoc Trapianto Cellule Staminali
      • Roma, Italy
        • Dipartimento di Biotecnologie Cellulari ed Ematologia, "Sapienza", Università di Roma
      • San Giovanni Rotondo, Italy
        • Ente Ecclesiastico Casa Sollievo Della Sofferenza - San Giovanni Rotondo - Ematologia
      • Udine, Italy
        • Asui Di Udine - Presidio Ospedaliero "Santa Maria Della Misericordia" - Clinica Ematologica

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

AML patients previously enrolled in GIMEMA studies for AML treatment

Description

Inclusion Criteria:

  • Signed written informed consent according to ICH/EU/GCP and national local laws (if applicable).
  • Patients aged ≥18 years affected by AML according to the FAB criteria, previously enrolled in GIMEMA Studies for AML treatment. AML patients with CNS involvement defined by the confirmation of leukemic blast cells in the centrifuged cerebrospinal fluid (CSF) with the presence of more than five WBCs in the CSF or the detection of a CNS granulocytic sarcoma using computed tomography or magnetic resonance imaging.

Exclusion Criteria:

  • Patients with acute promyelocytic leukemia (FAB M3 subtype), antecedent haematological diseases or therapy-related AML.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
AML patients
AML patients according to the French-American-British (FAB) criteria, previously enrolled in GIMEMA Studies for AML treatment. AML patients with CNS involvement defined by the confirmation of leukemic blast cells in the centrifuged cerebrospinal fluid (CSF) with the presence of more than five WBCs in the CSF or the detection of a CNS granulocytic sarcoma using computed tomography or magnetic resonance imaging.
Other: Observation of CNS involvement
AML patients with CNS involvement defined by the confirmation of leukemic blast cells in the centrifuged cerebrospinal fluid (CSF) with the presence of more than five WBCs in the CSF or the detection of a CNS granulocytic sarcoma using computed tomography or magnetic resonance imaging.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of CNS relapses
Time Frame: At 12 months from study start
To estimate the association between biological and clinical characteristic at diagnosis and the occurrence of CNS relapse and to confirm predisposing factors already described in literature (young age, higher level of lactate dehydrogenase; WBC counts at diagnosis, FAB M4 and M5 morphology, chromosome 16 inversion and chromosome 11 abnormality) in AML patients previously registered in GIMEMA Studies and treated according to the GIMEMA AML protocols
At 12 months from study start

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of patients in complete response
Time Frame: At 12 months from study start
Estimation of the association between presence of CNS involvement at diagnosis and during the course of the disease, in terms of CR rate, Overall Survival (OS) and Disease Free Survival (DFS).
At 12 months from study start
Number of patients alive
Time Frame: At 12 months from study start
Estimation of the association between presence of CNS involvement at diagnosis and during the course of the disease, in terms of CR rate, Overall Survival (OS) and Disease Free Survival (DFS).
At 12 months from study start

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Gruppo Italiano Malattie EMatologiche dell'Adulto

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Alessandro Pulsoni, Dipartimento di Biotecnologie Cellulari ed Ematologia, "Sapienza", Università di Roma
  • Study Director: Livio Pagano, Dipartimento di Biotecnologie Cellulari ed Ematologia, "Sapienza", Università di Roma

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 19, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 5, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 5, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 11, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 18, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 25, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 26, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 24, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AML1617

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Acute Myeloid Leukemia

Clinical Trials on Observation of CNS involvement

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings