Clinical trial NCT06337331: Adding Venetoclax to the High-dose Chemotherapy Regimen Prior to Mismatche Allogeneic Stem Cell Transplant
Official title: A Phase II Trial of Venetoclax-Enhanced Reduced Intensity HLA-Mismatched Allogeneic Transplant for Ultra-High-Risk Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndromes
Lead sponsor: Northside Hospital, Inc.
Sponsor class: OTHER
First posted: 2024-03-29
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of relapse/progression by conducting blood and bone marrow biopsy evaluations at one-year post-transplant
timeFrame: 12 months
Secondary outcomes:
measure: Number of patients alive at one-year post transplant
timeFrame: 12 months
measure: Number of patients alive without recurrence of disease at one-year post transplant by conducting blood and bone marrow biopsy procedures
timeFrame: 12 months
measure: Number of patients who died one year post-transplant not related to recurrence of disease
timeFrame: 12 months
measure: Number of patients who fully engrafted (blood counts fully recovered) by conducting chimerism studies at 30-, 60-, 90-, 180-, and 365-days post transplant
timeFrame: 12 months
measure: 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
timeFrame: 12 months
measure: 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
timeFrame: 12 months
measure: Number of patients who are alive at one-year post transplant who also did not develop GVHD
timeFrame: 12 months
measure: Number of patients with treatment-related adverse events to venetoclax as assessed by CTCAE v5.0
timeFrame: 12 months
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Caitlin Guzowski
state: Georgia
Study officials:
affiliation: Northside Hospital/BMTGA
name: Scott Solomon, MD
role: PRINCIPAL_INVESTIGATOR
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