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

NCT ID: NCT05799079

Last Updated: 2026-01-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-13
• Study Completion Date: 2024-09-20

Brief Summary

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.

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.

Conditions

Recurrent Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Given by mouth

Decitabine

Intervention Type: DRUG

Given by mouth

Cedazuridine

Intervention Type: DRUG

Given by mouth

Bone Marrow Aspiration and Biopsy

Intervention Type: PROCEDURE

Undergo bone marrow biopsy

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Interventions

Venetoclax

Given by mouth

Intervention Type: DRUG

Decitabine

Given by mouth

Intervention Type: DRUG

Cedazuridine

Given by mouth

Intervention Type: DRUG

Bone Marrow Aspiration and Biopsy

Undergo bone marrow biopsy

Intervention Type: PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Comprehensive Cancer Network

NETWORK

Sponsor Role: collaborator

Taiho Oncology, Inc.

INDUSTRY

Sponsor Role: collaborator

Sanjay Mohan

OTHER

Sponsor Role: lead

Responsible Party

Sanjay Mohan

Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Sanjay Mohan, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University/Ingram Cancer Center

Locations

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

VICCHEM2163

Identifier Type: -

Identifier Source: org_study_id