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

Related Clinical Trial
Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Decitabine as Maintenance Therapy After Standard Therapy in Treating Patients With Previously Untreated Acute Myeloid Leukemia Donor Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia in Remission S0432 Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission Combination Chemotherapy With or Without Valspodar in Treating Patients With Previously Untreated Acute Myeloid Leukemia Tipifarnib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Bortezomib, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia Comparing Three Different Combination Chemotherapy Regimens in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed, Previously Untreated Acute Myeloid Leukemia Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Relapsed or Refractory Acute Leukemia AKT Inhibitor MK-2206 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Early Discharge and Outpatients Care in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia Previously Treated With Intensive Chemotherapy Bortezomib, Mitoxantrone, Etoposide, and Cytarabine in Relapsed or Refractory Acute Myeloid Leukemia Vorinostat, Azacitidine, and Gemtuzumab Ozogamicin for Older Patients With Relapsed or Refractory AML Trebananib With or Without Low-Dose Cytarabine in Treating Patients With Acute Myeloid Leukemia Cholecalciferol in Treating Patients With Acute Myeloid Leukemia Undergoing Intensive Induction Chemotherapy Alvocidib, Cytarabine, and Mitoxantrone Hydrochloride or Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Metformin+Cytarabine for the Treatment of Relapsed/Refractory AML Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Lithium Carbonate and Tretinoin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Ixazomib (MLN9708) in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Omacetaxine Mepesuccinate, Cytarabine, and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Lenalidomide and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Choline Magnesium Trisalicylate and Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia AML Therapy With Irradiated Allogeneic Cells Decitabine, Cytarabine, and Daunorubicin Hydrochloride in Treating Patients With Acute Myeloid Leukemia Busulfan, Fludarabine Phosphate, and Anti-Thymocyte Globulin Followed By Donor Stem Cell Transplant and Azacitidine in Treating Patients With High-Risk Myelodysplastic Syndrome and Older Patients With Acute Myeloid Leukemia Azacitidine and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia Tipifarnib in Treating Patients With Acute Myeloid Leukemia in Remission Genetic and Molecular Characteristics of Mexican Adults With Acute Myeloid Leukemia: a Prospective Multicentric Study. Cytarabine With or Without SCH 900776 in Treating Adult Patients With Relapsed Acute Myeloid Leukemia Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia Studying Biomarkers in Samples From Younger Patients With Acute Myeloid Leukemia Central Nervous System (CNS) Involvement in Acute Myeloid Leukemia (AML)

Brief Title

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

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

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.
    

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

Observational


Primary Outcome

Number of CNS relapses

Secondary Outcome

 Number of patients in complete response

Condition

Acute Myeloid Leukemia

Intervention

Observation of CNS involvement

Study Arms / Comparison Groups

 AML patients
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Other

Estimated Enrollment

87

Start Date

December 2018

Completion Date

July 2019

Primary Completion Date

July 2019

Eligibility 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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Alessandro Pulsoni, +39 0670390514, [email protected]

Location Countries

Italy

Location Countries

Italy

Administrative Informations


NCT ID

NCT03410407

Organization ID

AML1617


Responsible Party

Sponsor

Study Sponsor

Gruppo Italiano Malattie EMatologiche dell'Adulto


Study Sponsor

Alessandro Pulsoni, Study Chair, Dipartimento di Biotecnologie Cellulari ed Ematologia, "Sapienza", Università di Roma


Verification Date

October 2018