Decitabine and Cedazuridine in Combination With Venetoclax for the Treatment of Patients Who Have Relapsed Acute Myeloid Leukemia After Donor Stem Cell Transplant

Phase 2 Study of Decitabine and Cedazuridine in Combination With Venetoclax for AML Relapse After Allogeneic Hematopoietic Cell Transplantation

This phase II trial tests how well decitabine and cedazuridine (DEC-C) works in combination with venetoclax in treating acute myeloid leukemia (AML) in patients whose AML has come back after a period of improvement (relapse) after a donor stem cell transplant. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving DEC-C in combination with venetoclax may kill more cancer cells in patients with relapsed AML.

Study Overview

• Status: Terminated
• Conditions: Recurrent Acute Myeloid Leukemia
• Intervention / Treatment: Procedure: Biospecimen Collection; Drug: Venetoclax; Drug: Decitabine; Drug: Cedazuridine; Procedure: Bone Marrow Aspiration and Biopsy

Detailed Description

PRIMARY OBJECTIVE:

I. To assess the effect of DEC-C/venetoclax on the investigator-assessed composite complete remission (CR) rate (CR/complete remission with partial hematologic recovery [CRh]/complete remission with incomplete hematologic recovery [CRi]).

SECONDARY OBJECTIVES:

I. To assess the rate of partial response (PR) and morphologic leukemia free state (MLFS) following treatment with DEC-C/venetoclax. II. To assess the relapse free survival of patients treated with DEC-C/venetoclax.

III. To assess overall survival of patients treated with DEC-C/venetoclax. IV. To assess the safety and tolerability of DEC-C/venetoclax in the post-hematopoietic cell transplant (HCT) setting.

V. To assess the rates of measurable residual disease negativity in patients achieving a CR.

OUTLINE:

Patients receive venetoclax orally (PO) daily for 28 days in a 28-day cycle. Patients receive DEC-C PO daily on days 1-5 of a 28-day cycle. Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University/Ingram Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >= 18 years at the time of signing the Informed Consent Form (ICF); must voluntarily sign an ICF and meet all study requirements
• History of morphologically confirmed AML (per World Health Organization [WHO] diagnostic criteria) with evidence of disease recurrence (>= 5% blasts consistent with prior disease) that occurs after allogeneic hematopoietic cell transplantation (HCT). Patients transplanted for another indication (e.g., myelodysplastic syndrome/chronic myelomonocytic leukemia [MDS/CMML]) who relapse with AML are eligible to enroll
• White blood cells (WBC) must be less than 25,000/ul for at least three days prior to cycle 1, day 1 (C1D1) (hydroxyurea allowed)
• A bone marrow biopsy must be performed and tissue collected for entrance to the trial
• Eastern Cooperative Oncology Group Performance Status of 0 - 2
• Alanine transaminase (ALT) serum glutamic pyruvic transaminase (SGPT) and/or aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) less than or equal to 3x upper limit of normal (ULN)

• Total bilirubin < 1.5 x ULN

  * Patients with Gilbert's syndrome (hereditary indirect hyperbilirubinemia) must have a total bilirubin of < 3 x ULN

• Calculated creatinine clearance >= 30 ml/min (per the Cockroft-Gault formula)
• Willingness to abide by all study requirements, including contraception, maintenance of a pill diary, and acceptance of recommended supportive care medications

Exclusion Criteria:

• Prior relapse or progression while receiving venetoclax or other commercially available or investigational BCL-2 inhibitor
• Anticancer therapy, including investigational agents =< 2 weeks or =< 5 half-lives of the drug, whichever is shorter, prior to C1D1. (Use of hydroxyurea is permitted)
• Inadequate recovery from toxicity attributed to prior anti-cancer therapy to =< Grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version [v]5.0), excluding alopecia or fatigue
• History of allogeneic HCT, or other cellular therapy product, within 3 months of signing consent
• Clinically active acute or chronic graft versus host disease (GVHD). Patients must be off calcineurin inhibitors for at least 4 weeks to be eligible
• Radiation therapy or major surgery within 3 weeks of signing consent
• Active, uncontrolled infection. Patients with infection under active treatment and controlled with antibiotics are eligible. Prophylaxis is acceptable
• Inability to tolerate oral medication, presence of poorly controlled gastrointestinal disease, or dysfunction that could affect study drug absorption
• Active documented central nervous system leukemia
• Concurrent treatment with a non-permitted concomitant medication
• Other malignancy IF currently being treated or likely to be treated in next 6 months except for basal or squamous cell carcinoma of the skin or cervical carcinoma in situ
• Pregnancy or breastfeeding females
• Known chronic alcohol or drug abuse
• Clinically significant cardiovascular disease with major event or cardiac intervention within the past 6 months (e.g. percutaneous intervention, coronary artery bypass graft, documented cardiac heart failure) as determined by the investigator
• Any other condition deemed by the investigator to make the patient a poor candidate for clinical trial and/or treatment with investigational agents

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (Venetoclax, DEC-C); Patients receive venetoclax PO daily for 28 days in a 28-day cycle. Patients receive DEC-C PO daily on days 1-5 of a 28-day cycle. Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.	Procedure: Biospecimen Collection; Undergo blood sample collection; Drug: Venetoclax; Given by mouth; Drug: Decitabine; Given by mouth; Drug: Cedazuridine; Given by mouth; Procedure: Bone Marrow Aspiration and Biopsy; Undergo bone marrow biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants That Achieved a Complete Response to Therapy	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants That Achieved a Partial Response to Therapy		9 months
Rate of Morphologic Leukemia Free State (MLFS) Following Treatment With DEC-C/Venetoclax		Up to 24 months post-treatment.
Rate of Relapse Free Survival	Relapse free survival was estimated by the Kaplan-Meier Method	Up to 24 months post-treatment.
Rate of Overall Survival	Overall survival was estimated using the Kaplan-Meier method.	Up to 24 months post-treatment.
Number of Treatment-related Adverse Events	List of adverse events that were attributed as related to study treatment is reported. All occurrences of a particular adverse event is reported.	The one patient that was enrolled on the study was on treatment for 3 months and adverse event data were followed during treatment and 35 days after completing treatment.
Rate of Measurable Residual Disease Negativity in Patients Achieving a CR		Up to 24 months post-treatment.

Collaborators and Investigators

• Sponsor: Sanjay Mohan
• Collaborators: National Comprehensive Cancer Network; Taiho Oncology, Inc.
• Investigators: Principal Investigator: Sanjay Mohan, MD, Vanderbilt University/Ingram Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2023
• Primary Completion (Actual): September 20, 2024
• Study Completion (Actual): September 20, 2024

Study Registration Dates

• First Submitted: March 22, 2023
• First Submitted That Met QC Criteria: March 22, 2023
• First Posted (Actual): April 5, 2023

Study Record Updates

• Last Update Posted (Actual): January 9, 2026
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Nucleic Acids, Nucleotides, and Nucleosides; Cytodiagnosis; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Diagnostic Techniques, Surgical; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; Decitabine; Biopsy; venetoclax; cedazuridine
• Other Study ID Numbers: VICCHEM2163

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No