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

March 29, 2024 updated by: Northside Hospital, Inc.

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)

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 Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

23

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Caitlin Guzowski

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: High-dose Chemotherapy + Mismatched Allogeneic Stem Cell Transplant
Drug: Venetoclax
400mg/day PO Days -8 to -2
Drug: Decitabine
20mg/m2/day IV Days -7 to -3
Drug: Fludarabine
30mg/m2/day IV Days -7 to -3
Drug: Busulfan
3.2mg/kg/day IV Days -5 to -4
Radiation: Total Body Irradiation
200cGy Day -2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of relapse/progression by conducting blood and bone marrow biopsy evaluations at one-year post-transplant
Time Frame: 12 months
12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of patients alive at one-year post transplant
Time Frame: 12 months
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
12 months
Number of patients who died one year post-transplant not related to recurrence of disease
Time Frame: 12 months
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
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
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
12 months
Number of patients who are alive at one-year post transplant who also did not develop GVHD
Time Frame: 12 months
12 months
Number of patients with treatment-related adverse events to venetoclax as assessed by CTCAE v5.0
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northside Hospital, Inc.

Investigators

  • Principal Investigator: Scott Solomon, MD, Northside Hospital/BMTGA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 31, 2024

Primary Completion (Estimated)

August 31, 2026

Study Completion (Estimated)

August 31, 2027

Study Registration Dates

First Submitted

March 22, 2024

First Submitted That Met QC Criteria

March 22, 2024

First Posted (Actual)

March 29, 2024

Study Record Updates

Last Update Posted (Actual)

April 2, 2024

Last Update Submitted That Met QC Criteria

March 29, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NSH 1401

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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