Combining decitabine, cedazuridine, and venetoclax for relapsed acute myeloid leukemia after stem cell transplant

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

This study is testing a new combination of three medications for people with relapsed acute myeloid leukemia after a stem cell transplant to see if it helps them feel better and live longer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 51 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Vanderbilt-Ingram Cancer Center (other)
• Drugs / interventions: Radiation
• Locations: 1 site (Nashville, Tennessee)
• Trial ID: NCT05799079 on ClinicalTrials.gov

What this trial studies

This phase II trial evaluates the effectiveness of a combination treatment involving decitabine, cedazuridine, and venetoclax for patients with relapsed acute myeloid leukemia (AML) following donor stem cell transplantation. The study aims to assess the composite complete remission rate, partial response rates, and overall survival among participants. Patients will receive oral venetoclax daily for 28 days alongside decitabine and cedazuridine during the first five days of each cycle. Additionally, bone marrow biopsies and blood samples will be collected to monitor treatment effects and safety.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a history of relapsed acute myeloid leukemia after allogeneic hematopoietic cell transplantation.

Not a fit: Patients with AML who have not undergone a stem cell transplant or those with other underlying conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve remission rates and overall survival for patients with relapsed AML after stem cell transplant.

How similar studies have performed: Other studies have shown promising results with similar combination therapies in treating relapsed AML, indicating potential for success.

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

Where this trial is running

Nashville, Tennessee

• Vanderbilt University/Ingram Cancer Center — Nashville, Tennessee, United States (RECRUITING)

Study contacts

• Principal investigator: Sanjay Mohan, MD — Vanderbilt University/Ingram Cancer Center
• Study coordinator: Vanderbilt-Ingram Services for Timely Access

Conditions: Recurrent Acute Myeloid Leukemia