Metronomic Decitabine-Cedazuridine and Venetoclax therapy for relapsed/refractory AML and high-risk blood cancers

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

In this single-center randomized phase 2 study, eligible adults with relapsed/refractory AML, high-risk MDS, or high-risk accelerated-phase MPN are randomized 1:1 to receive either DEC-C+VEN or AZA+VEN. Patients are stratified by disease type and treated until disease progression or intolerable toxicity, or until a stem-cell transplant is performed. The trial aims to compare response and safety between the regimens in an open-label design. Enrollment is limited to institutions within a single center, with Virginia Commonwealth University as the lead site. Outcomes will help determine whether a metronomic decitabine-cedazuridine schedule offers similar or superior activity to standard azacitidine-based therapy when combined with venetoclax.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Age ≥18 years at time of enrollment
* Diagnosis of one of the following by World Health Organization (WHO) International Consensus Classification (ICC) criteria as determined by local assessment:

  * Relapsed/ refractory acute myeloid leukemia (R/R AML) as defined by ≥5% marrow blasts or unequivocal, measurable extramedullary disease
  * High Risk Myelodysplastic Syndrome (HR-MDS) (high/very high risk MDS by Revised International Prognostic Scoring System (IPSS-R) or Molecular International Prognostic Scoring System (IPSS-M)
  * high-risk accelerated-phase myeloproliferative neoplasm (HR/AP-MPN) defined by ≥10% blasts in blood or bone marrow
* Eastern Cooperative Oncology Group (ECOG) Performance status 0-3
* White blood cell (WBC) count ≤25 × 109/Liter (L) (cytoreduction with hydroxyurea or steroids is allowed to achieve this)
* Aspartate Aminotransferase (AST)/ Alanine Aminotransferase (ALT) ≤3 × upper limit of normal (ULN) (≤5 × ULN if due to leukemic involvement)
* Total bilirubin ≤2 × ULN (unless the elevation is due to Gilbert's or hemolysis)
* Creatinine clearance ≥ 30 milliliters / minute (mL/min)
* Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of non-childbearing potential are those who have had a hysterectomy or bilateral oophorectomy, or who have completed menopause (no menses for at least one year and age ≥65 or follicle-stimulating hormone levels in the menopausal range).
* Subjects and their partners with reproductive potential must agree to use effective contraceptive measures during the study and for 3 months after the last dose of study treatment. Effective contraception includes methods such as oral contraceptives or double-barrier method.

Exclusion Criteria:

* Prior use of hypomethylating agent and venetoclax in combination (Note, use of hypomethylating agent and/or venetoclax separately in alternative combinations with other drugs is allowed)
* Inability to tolerate oral therapies, or medical co-morbidities that significantly impact parenteral absorption
* Acute promyelocytic leukemia myeloproliferative neoplasm (MPN) with the Philadelphia chromosome translocation (BCR:ABL) translocation
* Clinically significant cardiovascular disease as defined by unstable angina
* New York Heart Association class III/IV congestive heart failure
* Treatment with any investigational drug or therapy within 2 weeks of study treatment or 5 half-lives before the first dose of study treatment, whichever is shorter
* Known hypersensitivity to azacitidine, venetoclax, decitabine or cedazuridine
* Cytotoxic chemotherapy or prior azacitidine or decitabine within 2 weeks of first dose of study treatment
* Concurrent use of AML/MDS/MPN therapies including lenalidomide, erythropoietin, luspatercept, cytotoxic chemotherapies, targeted agents, etc Note: hydroxyurea is allowed in Cycle 1 if necessary for cytoreduction and/or cytarabine not exceeding a maximum dose of 1 gram per meter squared (g/m2) in Cycle 1 is also allowed for cytoreduction
* Uncontrolled intercurrent illness or infection (those with controlled HIV, hepatitis, or other chronic infections are eligible)
* Untreated central nervous system disease
* Pregnancy or breastfeeding
* Other active malignancy requiring systemic therapy during duration of trial or otherwise would confound endpoints (eg, second malignancy present where survival is expected to be less than 6 months)

Where it's running

• Virginia Commonwealth University
  Richmond, Virginia, United States Recruiting

Study contacts

• Principal investigator: Keri Maher, DO — Virginia Commonwealth University
• Study coordinator: Massey IIT Research Operations
• Email: masseyepd@vcu.edu
• Phone: 804-628-6430

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.