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

NCT ID: NCT01541280

Last Updated: 2016-03-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2015-07-31

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.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Azacitidine

Azacitidine (AZA) is to be administered every 28 days beginning day +56 to 100 posttransplant for one year provided the patients has a platelet count of \>15 x 109/L without transfusion for at least 2 successive days, and an absolute neutrophil count of \>1 x 109/L without growth factor for at least 2 successive days, and no acute GVHD greater than grade I and no clinical evidence of life-threatening infection. AZA is given 32 mg /m²/day subcutaneously for 5 days every 28 days (

Intervention Type: DRUG

DLI

Donor lymphocyte infusion (DLI) is to be given from day +126 (week 18) in patients without immunosuppressive therapy for at least one month and following 3 cycles of AZA, and without clinical signs of GVHD, and without uncontrolled infection and without a recent history of >grade 2 acute GVHD. DLI are schedules every 8 weeks. There are 3 DLI scheduled.

If first cycle of AZA is postponed beyond day 56 (maximum to Day 100), all subsequent cycles and DLI will be post poned too.

Intervention Type: OTHER

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

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nantes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Milpied Noel, Professor

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Bordeaux

Guillaume Thierry, Doctor

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Yakoub-Agha Ibrahim, Professor

Role: PRINCIPAL_INVESTIGATOR

CHU Lille

Huynh Anne, Doctor

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Blaise Didier, Professor

Role: PRINCIPAL_INVESTIGATOR

Institut Paoli Calmettes, Marseille

Mohamad Mothy, Professor

Role: PRINCIPAL_INVESTIGATOR

Hôpital Saint Antoine

Locations

University Hospital of Nantes

Nantes, , France

Countries

France

Other Identifiers

BRD 10/07-H

Identifier Type: -

Identifier Source: org_study_id