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

Phase 2

Withdrawn

• Conditions: Myelodysplastic Syndromes; Acute Myeloid Leukemia
• Interventions: Drug: Venetoclax; Drug: Decitabine; Drug: Fludarabine; Drug: Busulfan; Radiation: Total Body Irradiation

• Registration Number: NCT06337331
• Lead Sponsor: Northside Hospital, Inc.

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2024-03-22
• Study First Submitted QC: 2024-03-22
• Study First Posted: 2024-03-29
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-12
• Last Update Posted: 2024-06-14
• Study Start: 2024-08-31
• Primary Completion: 2026-08-31
• Study Completion: 2027-08-31

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
High-dose Chemotherapy + Mismatched Allogeneic Stem Cell Transplant	Busulfan	-
High-dose Chemotherapy + Mismatched Allogeneic Stem Cell Transplant	Total Body Irradiation	-
High-dose Chemotherapy + Mismatched Allogeneic Stem Cell Transplant	Decitabine	-
High-dose Chemotherapy + Mismatched Allogeneic Stem Cell Transplant	Venetoclax	-
High-dose Chemotherapy + Mismatched Allogeneic Stem Cell Transplant	Fludarabine	-

Primary Outcome Measures

Name	Time	Method
Incidence of relapse/progression by conducting blood and bone marrow biopsy evaluations at one-year post-transplant	12 months

Secondary Outcome Measures

Name	Time	Method
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
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
Number of patients alive at one-year post transplant	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	12 months
Number of patients who died one year post-transplant not related to recurrence of disease	12 months
Number of patients who are alive at one-year post transplant who also did not develop GVHD	12 months
Number of patients alive without recurrence of disease at one-year post transplant by conducting blood and bone marrow biopsy procedures	12 months
Number of patients with treatment-related adverse events to venetoclax as assessed by CTCAE v5.0	12 months

Trial Locations

Locations (1)

Caitlin Guzowski; 🇺🇸 Atlanta, Georgia, United States