New hope for hard-to-treat leukemia: three-drug combo targets relapsed AML

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

* Inclusion Criteria * Participants with relapsed/refractory AML (according to European LeukemiaNet 2022 Criteria) after treatment with a Venetoclax-containing regimen. * Participants with MDS, MPN, or MDS/MPN overlap who develop secondary AML after treatment with a Venetoclax-containing regimen. * Prior therapy with hydroxyurea or emergency use of Cytarabine (up to 1 gm total dose) for cytoreduction is allowed. * Prior hematopoietic stem-cell transplant (HSCT) and/or donor lymphocyte infusion (DLI) are allowed if at the time of relapse ≥ 90 days have passed from the date of the last stem cell transplant (90-day duration not required for DLI). * Age ≥ 18 years old. * Eastern Oncology Group (ECOG) performance status of ≤ 2 * Participants must agree to take the following reproductive precautions: * Negative urine pregnancy test within one week prior to starting the study therapy for all women of childbearing potential. * Participants who could become pregnant should use effective contraception during therapy and for 6 months after the last dose of study treatments. Participants with partners who could become pregnant should also use effective contraception during therapy and for 6 months after the last dose of study treatments. * Nursing women should discontinue breastfeeding during therapy and for 10 days after the last dose of study treatments. * Adequate organ function as follows: * liver function (bilirubin \< 2mg/dL, AST and/or ALT \<3 x ULN). Unless liver enzyme abnormalities are suspected by the treating investigator to be due to leukemic infiltration after discussion with the principal investigator (PI). * kidney function (creatinine \< 1.5 x ULN) * Ability to understand the study procedures and requirements. A signed informed consent by the participant or an authorized legal representative is required. * Exclusion Criteria * Pregnant or breastfeeding women * Uncontrolled active infections, i.e., signs of severe sepsis or hemodynamic instability * Concurrent diagnosis with another active malignancy (indolent or adequately treated malignancies are allowed after discussion with the PI. * Decompensated organ failure * Documented hypersensitivity to any of the study treatments * Participants with a diagnosis of acute promyelocytic leukemia (APL) * Recipients of previous HSCT who have \> grade 1 graft versus host disease (GVHD) of the gastro-intestinal tract, liver, lung or skin. * Prior therapy with purine analogues (Fludarabine, Clofarabine or Cladribine) unless it was part of a prior HSCT conditioning regimen.