Adding Venetoclax to the High-dose Chemotherapy Regimen Prior to Mismatche Allogeneic Stem Cell Transplant

Northside Hospital, Inc.

Overview

Patients eligible for a mismatch allogeneic stem cell transplant will receive Venetoclax daily for 7 days prior to transplant in addition to the following chemotherapy regimen: Decitabine daily for 5 days, Fludarabine daily for 5 days, and Busulfan daily for 2 days followed by 1 day of total body irradiation. Stem cell transplant will occur thereafter.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Conditions

Acute Myeloid Leukemia Myelodysplastic Syndromes

Interventions

VenetoclaxDRUG

400mg/day PO Days -8 to -2

DecitabineDRUG

20mg/m2/day IV Days -7 to -3

FludarabineDRUG

30mg/m2/day IV Days -7 to -3

Busulfan

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Availability of a 4/8 - 6/8 HLA-matched related donor or a 7/8 HLA-matched unrelated donor * Receiving first allogeneic transplant * KPS \>/= 70% * MDS associated with TP53 mutation AND R-IPSS high or very high risk at diagnosis OR * AML with adverse risk cytogenetics or molecular abnormalities according to the 2017 ELN risk stratification OR pre-transplant MRD by either flow cytometry, cytogenetics or FISH * Less than 5% myeloblasts in the marrow pre-transplant Exclusion Criteria: * Poor cardiac function defined as LVEF \<45% * Poor pulmonary function defined as FEV1, FVC, or DLCO \<50% predicted * Poor liver function defined as bilirubin \>/=2.5mg/dL, AST/ALT \>3xULN * Poor renal function defined as creatinine \>/=2.0mg/dL or CrCl \<40mL/min * Ongoing or active systemic infection, active Hepatitis B or C virus infection, or known HIV positivity * Patient requiring treatment with a moderate or strong inhibitor or inducer of CYP3A4 or a P-gp inhibitor within 7 days prior to starting preparative chemotherapy through Day +4 post-transplant

Locations (1)

Caitlin Guzowski

Atlanta, Georgia, United States

Outcomes

Primary Outcomes

Incidence of relapse/progression by conducting blood and bone marrow biopsy evaluations at one-year post-transplant

Time frame: 12 months

Secondary Outcomes

Number of patients alive at one-year post transplant

Time frame: 12 months

Number of patients alive without recurrence of disease at one-year post transplant by conducting blood and bone marrow biopsy procedures

Time frame: 12 months

Number of patients who died one year post-transplant not related to recurrence of disease

Time frame: 12 months

Number of patients who fully engrafted (blood counts fully recovered) by conducting chimerism studies at 30-, 60-, 90-, 180-, and 365-days post transplant

Time frame: 12 months

Number of patients who developed acute graft-versus-host disease by recording signs and symptoms of acute GVHD according to MAGIC standards at one-year post-transplant

Time frame: 12 months

Number of patients who developed chronic graft-versus-host disease by recording signs and symptoms of chronic GVHD according to NIH standards at one-year post-transplant

Time frame: 12 months

Number of patients who are alive at one-year post transplant who also did not develop GVHD

Time frame: 12 months

Number of patients with treatment-related adverse events to venetoclax as assessed by CTCAE v5.0

Time frame: 12 months

Data from ClinicalTrials.gov

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