Administration of 5-azacytidine and lymphocytes in patients in relapse after treatment by transplantation for a hematological cancer.

Phase 1

Active, not recruiting

• Conditions: MedDRA version: 18.0 Level: PT Classification code 10059034 Term: Acute myeloid leukaemia recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0 Level: HLT Classification code 10028536 Term: Myelodysplastic syndromes System Organ Class: 100000004851; Therapeutic area: Diseases [C] - Cancer [C04]; Acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) in relapse after allogeneic stem cell transplantation

• Registration Number: EUCTR2012-005535-90-BE
• Lead Sponsor: CHU Mont-Godinne

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-06-25
• Last Update Posted: 2020-02-01

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: Not specified
• Target Recruitment: 50

Inclusion Criteria

Patients :
-Age = 18 years.
-Be able to understand and sign informed consent.
-Fertile patients must use a reliable contraception method.

Disease status at transplantation :
-Acute myelogenous leukemia (AML) in first or subsequent complete remission (< 5% marrow blasts).
-Myelodysplastic syndrome (MDS) with less than 10% marrow blasts at the time of transplantation.

Transplantation :
-Allogeneic transplantation using a sibling or unrelated donor with matching in 10/10 alleles (HLA-A, B, C, DRB1, DQB1) or maximum of one allele or one antigen or 1 antigen + 1 allele or 1 antigen + 1 DQB1 antigen or 2 alleles mismatches.
-Standard or reduced-intensity conditioning.
-Second transplantation is allowed.
-Donor is willing to donate lymphocytes.

Clinical situation:
-Cytologic relapse after allo-stem cell transplantation defined as the recurrence of more than 5% blasts on bone marrow aspiration (AML) or evidence of MDS
-Immunophenotypic relapse defined as the recurrence of an abnormal phenotype on flow cytometry in bone marrow aspirate.
-Cytogenetic or molecular relapse defined as the persistence or recurrence of a cytogenetic abnormality or molecular marker in bone marrow aspiration or peripheral blood. WT1 expression is not considered as reliable marker for relapse in this protocol but FLT3-ITD, NPM1, CEBPA, or translocation-specific markers (such as MLL-PTD, AML-ETO, CBFB-MYH11) are.

Immunosuppressive therapy should have been stopped before inclusion.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

-More than 30% marrow blasts at the time of inclusion.
-Extramedullary relapse including central nervous involvement.
-ECOG Performance status > 2.
-Active acute grade II-IV GvHD at the time of inclusion.
-Active chronic GvHD requiring systemic therapy at the time of inclusion.
-Uncontrolled infection.
-HIV positive.
-Acute or chronic heart failure (NYHA class III or IV) or symptomatic ischemic heart disease or
ejection fraction < 35% or uncontrolled arrhythmia.
-Severe liver failure (total bilirubin > 3 mg/dL, SGPT > 4 X upper normal limit).
-Severe pulmonary failure (corrected DLCo < 35%).
-Terminal renal failure requiring dialysis.
-Severe neurological or psychiatric disorders.
-Concurrent investigational drug.
-Other treatment for relapse, except for hydroxyurea but it should be stopped before inclusion in the study.
-Female who is pregnant or breastfeeding.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the response rate to DLI by the combination with azacytidine in the population of patients with relapsed AML and MDS after allo-SCT. ;<br> Secondary Objective: - To evaluate disease-free survival at 2 years.<br> - To evaluate overall survival at 2 years.<br> - To assess the toxicity profile (hematological and non-hematological).<br> - To assess the incidence and severity of GvHD.<br> - To assess the incidence and severity of infections.<br> - To compare the study cohort to an historical group of patients with similar characteristics.<br> ;Primary end point(s): The overall response rate to the combination of azacytidine and DLI will be defined by the addition of complete remission and partial remission.;Timepoint(s) of evaluation of this end point: Will be evaluated at day 24 of cycle 1, 3 and 5. Then every 3 months for a year after cycle 6 thereafter at 1.5 and 2 years after cycle 6.