VIDAZA-DLI Pre-emptive Azacitidine and Donor Lymphocyte Infusions Following Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome (VIDAZA-DLI)

Pre-emptive Azacitidine and Donor Lymphocyte Infusions Following Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome

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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndrome
• Intervention / Treatment: Drug: Azacitidine; Other: DLI

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44000
    • University Hospital of Nantes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the cumulative incidence of relapse rate	An A'Hern procedure will be used (cf. 11.1): If the number of patients not relapsed at two year will be 18 or more out of 24 patients, the null hypothesis will be rejected and the relapse rate will be considered acceptable.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of disease-free survival (DFS) at 2 years from transplantation	Kaplan-Meier method	2 years
Measure the overall survival rate at 2 years	Kaplan-Meier method	2 years
Cumulative incidence death from leukemia, and non relapse mortality (NRM)	cumulative incidence function for disease free survival at 2 years from transplantation, GVHD, death from leukaemia and non-relapse mortality will be estimated (patients are at risk not only for relapse but can also be "removed" from possible relapse because of competing events such as death in remission (due to infection or GVHD)).	2 years
Feasibility and safety of administrating maintenance azacitidine following allogenic transplantaton	To evaluate toxicity induced by the azacitidine and DLI, different parameters will be studied:Cell Blood Count with differential, liver function tests, serum creatinine, BUN and total protein will be performed weekly from the time of initiation of azacitidine administration until completion of the last DLI. Performance Status,Acute GVHD,Bone marrow aspiration with evaluation of morphological response as well as chimerism from peripheral blood will be performed prior starting azacitidine, following 3 cycles of azacitidine and after the seventh cycle and twelfth cycle of azacitidine.	2 years
Feasibility and safety of performing prophylactic donor lymphocytes infusion	The relatedness of observed toxicity to DLI will be evaluated and documented: Maximum toxicity with respect to mucositis, liver, kidney, lung, heart, neurological system according to CTC criteria (cf. appendices).; Infections (bacteremia, fungemia, invasive fungal infection, CMV reactivation and disease, other viral reactivation or infection).; Grade of acute and chronic GVHD (cf. appendices); GVHD is classified according to clinical symptoms, irrespective to the time interval to DLI.; Bone marrow aspiration, as well as chimerism in PB.	2 years
Incidence and severity of acute and chronic graft-versus-host disease	Symptoms related to GVHD should be reported within the GVHD section of the case reporting files. AE and SAE are documented in the patient's chart; on a daily basis, as long as the patient is on ward, and; on a weekly to two-monthly basis during outpatient follow up, depending on the frequency of outpatient visits on the respective patient.	2 years

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Principal Investigator: Milpied Noel, Professor, CHU Bordeaux; Principal Investigator: Guillaume Thierry, Doctor, CHU Nantes; Principal Investigator: Yakoub-Agha Ibrahim, Professor, CHU Lille; Principal Investigator: Huynh Anne, Doctor, CHU Toulouse; Principal Investigator: Blaise Didier, Professor, Institut-Paoli Calmettes Marseille; Principal Investigator: Mohamad Mothy, Professor, Hôpital Saint Antoine

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ACTUAL): July 1, 2015
• Study Completion (ACTUAL): July 1, 2015

Study Registration Dates

• First Submitted: December 13, 2011
• First Submitted That Met QC Criteria: February 23, 2012
• First Posted (ESTIMATE): February 29, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): March 18, 2016
• Last Update Submitted That Met QC Criteria: March 17, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Allogreffe, LAM , MDS; Azacitidine (VidazaÒ); Injection de lymphocytes de donneur (DLI)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: BRD 10/07-H