RightFit
RecruitingPhase 2

Metronomic Decitabine-Cedazuridine and Venetoclax in R/R AML, HR-MDS, HR/AP MPN

Metronomic Decitabine-Cedazuridine and Venetoclax in Relapsed/Refractory Acute Myeloid Leukemia R/R AML), High Risk Myelodysplastic Syndrome (HR-MDS), and High-Risk Myeloproliferative Neoplasms (HR/AP MPN)

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This phase 2 study tests decitabine-cedazuridine and venetoclax. It is for adults with acute myeloid leukemia (AML) that came back or did not respond to treatment, or certain high-risk blood cancers called MDS or MPN.

This is a single-center randomized phase 2 open-label clinical trial.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be age 18 or older.
  • Have AML that came back or resisted treatment, with at least 5% immature cancer cells in bone marrow or clear, measurable disease outside the marrow; high- or very-high-risk MDS; or high-risk accelerated-phase MPN with at least 10% immature cells in blood or marrow.
  • Have a score of 0–3 on a scale of daily activity and ability to care for yourself.
  • Have a white blood cell count of 25 billion per liter or less. Hydroxyurea or steroids may be used to lower it.
  • Have liver enzyme levels no more than 3 times the normal limit, or 5 times if leukemia causes the rise. Bilirubin must be no more than 2 times the normal limit, unless raised by Gilbert's syndrome or red blood cell breakdown.
  • Have kidney function of at least 30 milliliters per minute on a creatinine clearance test.
  • If able to become pregnant, have a negative pregnancy test and not be pregnant or breastfeeding.
  • You and your partner must use effective birth control if able to have children, during treatment and for 3 months after the last dose.

Who can't join

  • Past treatment with venetoclax together with a hypomethylating drug, a type of cancer drug. Use separately or in other drug combinations is allowed.
  • Cannot take medicines by mouth, or have a health problem that greatly affects drug absorption.
  • Have acute promyelocytic leukemia, a type of AML, or MPN with the Philadelphia chromosome (BCR:ABL) gene change.
  • Have unstable angina (heart-related chest pain) or severe heart failure.
  • Recently received an experimental treatment: within 2 weeks or the time for the drug level to drop by half 5 times, whichever is shorter. Also excluded: cell-killing chemotherapy, azacitidine, or decitabine within 2 weeks before study treatment.
  • Are using other AML, MDS, or MPN treatments. Hydroxyurea or limited-dose cytarabine may be allowed during the first treatment cycle to lower blood cell counts.
  • Have a known allergy to azacitidine, venetoclax, decitabine, or cedazuridine; an uncontrolled illness or infection; or untreated disease in the brain or spinal cord. Controlled HIV, hepatitis, or other long-term infections are allowed.
  • Are pregnant or breastfeeding, or have another active cancer that needs treatment throughout the body during the study or could affect the study results.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

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)

Study sites (1)

VA