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

Trial Title: 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

Condition: Recurrent Acute Myeloid Leukemia

Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Venetoclax
Decitabine

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Venetoclax
Description: Given by mouth
Arm group label: Treatment (Venetoclax, DEC-C)

Intervention type: Drug
Intervention name: Decitabine
Description: Given by mouth
Arm group label: Treatment (Venetoclax, DEC-C)

Intervention type: Drug
Intervention name: Cedazuridine
Description: Given by mouth
Arm group label: Treatment (Venetoclax, DEC-C)

Intervention type: Procedure
Intervention name: Bone Marrow Aspiration and Biopsy
Description: Undergo bone marrow biopsy
Arm group label: Treatment (Venetoclax, DEC-C)

Intervention type: Procedure
Intervention name: Biospecimen Collection
Description: Undergo blood sample collection
Arm group label: Treatment (Venetoclax, DEC-C)

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.

Criteria for 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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Vanderbilt University/Ingram Cancer Center

Address:
City: Nashville
Zip: 37232
Country: United States

Status: Recruiting

Contact:
Last name: Vanderbilt-Ingram Service for Timely Access

Phone: 800-811-8480
Email: cip@vumc.org

Investigator:
Last name: Sanjay Mohan, MD
Email: Principal Investigator

Start date: January 29, 2024

Completion date: March 2029

Lead sponsor:
Agency: Sanjay Mohan
Agency class: Other

Collaborator:
Agency: National Comprehensive Cancer Network
Agency class: Other

Collaborator:
Agency: Taiho Oncology, Inc.
Agency class: Industry

Source: Vanderbilt-Ingram Cancer Center

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05799079