Viewing Study NCT02252107



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Last Modification Date: 2024-10-26 @ 11:31 AM
Study NCT ID: NCT02252107
Status: COMPLETED
Last Update Posted: 2020-03-19
First Post: 2014-09-19

Brief Title: 10-day Decitabine Fludarabine and 2 Gray TBI as Conditioning Strategy for Poor and Very Poor Risk AML in CR1
Sponsor: Radboud University Medical Center
Organization: Radboud University Medical Center

Study Overview

Official Title: 10-day Decitabine Fludarabine and 2 Gray TBI as Conditioning Strategy for Poor and Very Poor Risk AML in CR1
Status: COMPLETED
Status Verified Date: 2018-10
Last Known Status: None
Delayed Posting: No
If Stopped, Why?: Not Stopped
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: None
Brief Summary: This study examines whether the addition of decitabine to the standard FluTBI conditioning regimen prior to allogeneic stem cell transplantation in poor and very poor risk AML patients reduces the risk of recurrence of the disease Because decitabine has hardly any side effects it will likely have little impact on the occurrence of Graft Versus Host Disease The investigators are looking for a pre-treatment for transplantation which reduces the chance of recurrence of the disease without involving severe damage to normal tissues
Detailed Description: Acute myeloid leukemia AML is a heterogeneous group of malignant hematological diseases with different molecular genetic abnormalities These are important in predicting response to treatment Recently an analysis of 424 AML patients treated in various HOVON protocols showed a 5 year overall survival for patients in good intermediate poor and very poor risk groups of 65 51 25 and 7 respectively HOVON 102 protocol This shows that especially for patients in the very poor risk group the outcome is very disappointing despite the current treatment strategies For patients with intermediate poor and very poor risk cytogenetics postconsolidation treatment with an allogeneic hematopoietic cell transplantation allo HCT is standard practice after myeloablative MAB HCT or non-myeloablative NMA HCT conditioning

Unfortunately mortality after MAB conditioning is still considerable mainly due to therapy related mortality graft-versus-host disease infections or relapse Currently the NMA conditioning is used more frequently which is far less toxic Nonmyeloablative regimens have relied on the immunological anti-leukemia effect graft-versus-leukemia to prevent relapsing disease This anti-leukemia effect however needs time to develop which makes it necessary to be in control over the disease pre-transplantation as much as possible This extends the time the immune system of the donor has to develop an adequate anti-leukemia effect which is especially important in the very poor risk group patients since they have the highest chance of relapse

Epigenetic alterations are increasingly recognised for their roles in oncogenesis These alterations can for example silencegenes by hypermethylation These alterations are potentially reversible

The hypomethylating agent decitabine is one of the therapeutic approaches which can reactivate silenced genes by its interaction on the epigenetics A phase II study Blum Proc Natl Acad Sci 2010 with 53 AML patients who received 10 days decitabine showed a complete remission rate CR in 47 of patients This percentage corresponds to the CR of intensive chemotherapy in elderly AML patients The median survival was 55 weeks Furthermore this study showed that decitabine was well tolerated

Earlier studies have shown that patients whose disease was controlled with hypomethylating agents pre-transplantation had comparable survival compared with patients whose disease was controlled with intensive chemotherapyDamaj Journal of Clinical Oncology 2012

In the current study the AML is already in remission after intensive chemotherapy In an attempt to design a conditioning strategy with very low toxicity but considerable myelosuppressive activity the investigators will combine the non-myeloablative NMA fludarabine and low-dose TBI 2 Gray with a 10-day schedule of decitabine Dec-Flu-TBI Theoretically it is very attractive to add a drug like decitabine in a 10-day schedule that exerts a strong antileukemic effect without additional extra-medullary toxicity to the standard Flu-TBI NMA conditioning regimen The hypothesis is that in this way the investigators can extent the time the immune system of the donor needs to create an adequate graft-versus-leukemia effect at the cost of low toxicity

Study Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: None
Is a FDA Regulated Device?: None
Is an Unapproved Device?: None
Is a PPSD?: None
Is a US Export?: None
Is an FDA AA801 Violation?: None