Clinical trial NCT01541280: VIDAZA-DLI Pre-emptive Azacitidine and Donor Lymphocyte Infusions Following Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome
Official title: Pre-emptive Azacitidine and Donor Lymphocyte Infusions Following Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndrome
Keywords: Allogreffe, LAM , MDS
Azacitidine (VidazaÒ)
Injection de lymphocytes de donneur (DLI)
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2012-02-29
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Patients included in the study with high risk acute myeloid leukemia or myelodysplastic syndrome as defined will receive an allogeneic transplantation conditioned by either myeloablative or reduced regimen. Following allogeneic transplantation, patients will receive a maintenance regimen combining chemotherapy with azacitidine (aza) and immunotherapy with donor lymphocyte infusion.


Eligibility criteria: Inclusion Criteria:

* Patients with high risk acute myeloid leukemia undergoing allogeneic transplantation with either a familial or an unrelated donor.

High risk AML is defined as :

* AML in CR1 with unfavorable cytogenetics defined by complex caryotype, autosomal monosomy combined or not with other cytogenetics abnormalities inv(3)/t(3,3), t(6;9), t(6;11), t(11;19), del(5q), del(7q).
* AML in CR2 or greater remission prior allogeneic transplantation
* AML in PR or relapse prior allogeneic transplantation
* Or Patients with high risk myelodysplastic syndrome undergoing allogeneic transplantation with either a familial or an unrelated donor.

High risk MDS is defined as :

* MDS with intermediate-2 group and higher risk group according to IPSS criteria
* Age 18 - 70 years.
* Availability of an HLA identical family donor or unrelated donor with matching in 10/10 alleles (HLA-A, B, C, DRB1, DQB1) or maximum of 1 allele or antigen mismatch OR family donor with maximum 1 allele mismatch.
* Conditioning regimen to allogeneic transplantation may be either myeloablative or reduced.
* Be able to understand and sign informed consent.
* Affiliation number to National Health Care System
* Men and women of childbearing potential must use effective contraception during and up to 3 months after treatment.

Exclusion Criteria:

* The presence of any one exclusion criteria renders the patient ineligible:
* Patient in full relapse post-transplant (\>20% blasts in the bone marrow) following allogeneic transplant
* Documented leukemic infiltration of CNS/cerebrospinal fluid.
* Karnofsky performance score below 60%.
* Acute and chronic heart failure (NYHA Class III or IV) or symptomatic ischemic heart disease.

following allogeneic transplant

* Severe liver failure (bilirubin \>30 μmoles/L, SGPT \> 4 X upper limit of normal).
* Hepatic malignancy in advanced stage.
* Severe neurological or psychiatric disorders
* Acute GVHD grade II-III. Patient with grade I GVHD may be included (see annex 1 for GHVD grade definition).
* Active uncontrolled infection.
* Denied informed consent.
* Treatment with other investigational drugs following allogeneic transplantation.
* No effective contraception
* Lactating females
* Pregnant woman

Primary outcomes:
measure: Evaluation of the cumulative incidence of relapse rate
timeFrame: 2 years
Secondary outcomes:
measure: Evaluation of disease-free survival (DFS) at 2 years from transplantation
timeFrame: 2 years
measure: Measure the overall survival rate at 2 years
timeFrame: 2 years
measure: Cumulative incidence death from leukemia, and non relapse mortality (NRM)
timeFrame: 2 years
measure: Feasibility and safety of administrating maintenance azacitidine following allogenic transplantaton
timeFrame: 2 years
measure: Feasibility and safety of performing prophylactic donor lymphocytes infusion
timeFrame: 2 years
measure: Incidence and severity of acute and chronic graft-versus-host disease
timeFrame: 2 years
Other outcomes:
Locations:
city: Nantes
country: France
facility: University Hospital of Nantes
Study officials:
affiliation: University Hospital, Bordeaux
name: Milpied Noel, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Nantes University Hospital
name: Guillaume Thierry, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Lille
name: Yakoub-Agha Ibrahim, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Toulouse
name: Huynh Anne, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut-Paoli Calmettes Marseille
name: Blaise Didier, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Saint Antoine
name: Mohamad Mothy, Professor
role: PRINCIPAL_INVESTIGATOR
References: