Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT03410407 |
| Other study ID # |
AML1617 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
March 19, 2019 |
| Est. completion date |
June 5, 2020 |
Study information
| Verified date |
October 2022 |
| Source |
Gruppo Italiano Malattie EMatologiche dell'Adulto |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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.
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.
