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

Acute Myeloid Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT06337331
• Other study ID #: NSH 1401
• Status: Withdrawn
• Phase: Phase 2
• Start date: August 31, 2024
• Est. completion date: August 31, 2027

Study information

• Verified date: June 2024
• Source: Northside Hospital, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 31, 2027
• Est. primary completion date: August 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• Venetoclax
400mg/day PO Days -8 to -2
• Decitabine
20mg/m2/day IV Days -7 to -3
• Fludarabine
30mg/m2/day IV Days -7 to -3
• Busulfan
3.2mg/kg/day IV Days -5 to -4

Radiation:
• Total Body Irradiation
200cGy Day -2

Locations

Country	Name	City	State
United States	Caitlin Guzowski	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Northside Hospital, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (26)

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* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of relapse/progression by conducting blood and bone marrow biopsy evaluations at one-year post-transplant		12 months
Secondary	Number of patients alive at one-year post transplant		12 months
Secondary	Number of patients alive without recurrence of disease at one-year post transplant by conducting blood and bone marrow biopsy procedures		12 months
Secondary	Number of patients who died one year post-transplant not related to recurrence of disease		12 months
Secondary	Number of patients who fully engrafted (blood counts fully recovered) by conducting chimerism studies at 30-, 60-, 90-, 180-, and 365-days post transplant		12 months
Secondary	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		12 months
Secondary	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		12 months
Secondary	Number of patients who are alive at one-year post transplant who also did not develop GVHD		12 months
Secondary	Number of patients with treatment-related adverse events to venetoclax as assessed by CTCAE v5.0		12 months