Study to assess venetoclax + azacitidine and donor lymphocyte infusion (DLI) in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in relapse after allohematopoietic stem cell transplantation (AHSCT).
A phase I-II study to assess venetoclax + azacitidine and donor lymphocyte infusion (DLI) in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in relapse after allohematopoietic stem cell transplantation (AHSCT).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
55
Venetoclax will be given once daily orally on days 1 to 14 for all cycles. Venetoclax + azacitidine +/- donor lymphocyte infusion (12 cycles maximum)
CHU d'Angers
Angers, France
CHU de Grenoble
Grenoble, France
Hôpital Dupuytren
Limoges, France
Hôpital Saint-Eloi
Montpellier, France
Phase I: Dose-finding study
Evaluation of Dose-limiting toxicity (DLT) to determine the optimal dose level in terms of both toxicity and safety for venetoclax + azacitidine
Time frame: At the end of cycle 1 of venetoclax + azacitidine (each cycle is 28 days)
Phase II: Overall improvement rate of venetoclax + azacitidine +/- DLI
Response assessment performed according to modified IWG (International Working Group) 2006 criteria for myelodysplastic syndrome and to European Leukemia Net criteria for acute myeloid leukemia
Time frame: After 8 cycles of venetoclax + azacitidine (each cycle is 28 days)
Toxicity assessment
Adverse events analyzed by frequency, NCI CTCAE 5.0 grade, and causality
Time frame: At 60 months (at end of study)
Graft-versus-Host-Disease (GVHD) rate
Acute and chronic graft-versus-host-disease (GVHD) rate assessment (graft-versus-host events analyzed by frequency and grade)
Time frame: At 60 months (at end of study)
Duration of response
Duration of response defined as time from the date of the first observed response (complete or partial) to the date of first subsequent documented disease progression or relapse or death
Time frame: At 60 months (at end of study)
Overall survival
Overall Survival defined as time from the date of the first dose of venetoclax to the date of death or end of study
Time frame: At 60 months (at end of study)
Progression-free survival
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CHU Hôtel Dieu
Nantes, France
Hôpital l'Archet I
Nice, France
Hôpital Saint louis
Paris, France
CHU de Haut-Lévèque
Pessac, France
Centre Hospitalier Lyon-Sud
Pierre-Bénite, France
Centre Henri Becquerel
Rouen, France
...and 1 more locations
Progression-free Survival for patients with at least a partial response defined as time from the date of the first dose of venetoclax to the date of the first documented disease progression or relapse or death
Time frame: At 60 months (at end of study)
Event-free survival
Event-free Survival defined as time from the date of the first dose of venetoclax to the date of earliest disease progression or death
Time frame: At 60 months (at end of study)