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

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ClinicalTrials.gov Identifier: NCT03410407
Recruitment Status : Recruiting
First Posted : January 25, 2018
Last Update Posted : October 14, 2020
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto

Brief Summary:
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.

Condition or disease Intervention/treatment
Acute Myeloid Leukemia Other: Observation of CNS involvement

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.

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Study Type : Observational
Estimated Enrollment : 87 participants
Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: Central Nervous System (CNS) Involvement in Acute Myeloid Leukemia (AML): an Observational Retrospective Multicentre Study on Patients Previously Registered in GIMEMA Clinical Trials
Actual Study Start Date : March 19, 2019
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020


Group/Cohort Intervention/treatment
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.




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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).

  2. 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).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
AML patients previously enrolled in GIMEMA studies for AML treatment
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03410407


Contacts
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Contact: Paola Fazi +39 0670390514 p.fazi@gimema.it
Contact: Enrico Crea +39 0670390514 e.crea@gimema.it

Locations
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Italy
Dipartimento di Biotecnologie Cellulari ed Ematologia, "Sapienza", Università di Roma Recruiting
Roma, Italy
Contact: Alessandro Pulsoni         
Principal Investigator: Alessandro Pulsoni         
Sponsors and Collaborators
Gruppo Italiano Malattie EMatologiche dell'Adulto
Investigators
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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
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Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier: NCT03410407    
Other Study ID Numbers: AML1617
First Posted: January 25, 2018    Key Record Dates
Last Update Posted: October 14, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
Acute Myeloid Leukemia
Central Nervous System
Relapse
Prognostic factors
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms