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

NCT01541280 | Completed Phase 2

• 1 other identifier: BRD 10/07-H
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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

Keywords

Allogreffe, LAM , MDS; Azacitidine (VidazaÒ); Injection de lymphocytes de donneur (DLI)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Evaluation of disease-free survival (DFS) at 2 years from transplantation

  2 years

• Measure the overall survival rate at 2 years

  2 years

• Cumulative incidence death from leukemia, and non relapse mortality (NRM)

  2 years

• Feasibility and safety of administrating maintenance azacitidine following allogenic transplantaton

  2 years

• Feasibility and safety of performing prophylactic donor lymphocytes infusion

  2 years

Interventions

Azacitidine DRUG

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 (

DLI OTHER

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.

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (1)

University Hospital of Nantes

Nantes, 44000, France

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Milpied Noel, Professor

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

• Guillaume Thierry, Doctor

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

• Yakoub-Agha Ibrahim, Professor

  CHU Lille

  PRINCIPAL INVESTIGATOR

• Huynh Anne, Doctor

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

• Blaise Didier, Professor

  Institut Paoli Calmettes, Marseille

  PRINCIPAL INVESTIGATOR

• Mohamad Mothy, Professor

  Hôpital Saint Antoine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2011
• First Posted: February 29, 2012
• Study Start: November 1, 2011
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: March 18, 2016

Record last verified: 2016-02

Locations

FR (1)