Quizartinib, Decitabine, and Venetoclax in Treating Participants With Untreated or Relapsed Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome
M.D. Anderson Cancer Center · M D Anderson Cancer Center, Houston, Texas
This phase I/II trial studies how well quizartinib, decitabine, and venetoclax work in treating participants with acute myeloid leukemia or high risk myelodysplastic syndrome that is untreated or has come back (relapsed). Quizartinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as decitabine and venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving quizartinib and decitabine may work better at treating acute myeloid leukemia and myelodysplastic syndrome.
Eligibility: 18 Years to · All · * Diagnosis of 1) AML (World Health Organization \[WHO\] classification definition of \>= 20% blasts) excluding acute promyelocytic leukemia (APL) or 2) MDS with \> 10% blasts (defined by the International Prognostic Scoring System \[IPSS\] classification). * For frontline Cohort: Patients aged \>= 60 years old who are not candidates for intensive induction therapy and agree to receive the proposed combination therapy will be enrolled. * Not considered candidates for intensive remission induction chemotherapy at time of enrollment based on EITHER: * 75 years of age OR * \< 75 years of age with at least 1 of the following: * Poor performance status (Eastern Cooperative Oncology Group \[ECOG\]) score of 2-3. * Clinically significant heart or lung comorbidities, as reflected by at least 1 of: * Left ventricular ejection fraction (LVEF) =\< 50%. * Lung diffusing capacity for carbon monoxide (DLCO) =\< 65% of expected. * Forced expiratory volume in 1 second (FEV1) =\< 65% of expected. * Chronic stable angina or congestive heart failure controlled with medication. * Liver transaminases \> 3 x upper limit of normal (ULN). * Other contraindication(s) to anthracycline therapy (must be documented). * Other comorbidity the investigator judges incompatible with intensive remission induction chemotherapy, which must be documented and approved by the principal investigator (PI). * Patients with newly diagnosed AML with poor risk complex karyotype and/or TP53 deletions/mutations equal or younger than 60 year old * For relapsed cohort: Patients aged \>= 18 years old. (Patients who are candidates for relapse cohort will be enrolled into the study regardless of their fitness for intensive chemotherapy). (a) Patients with relapsed/refractory AML are eligible if they are not eligible for potentially curative therapy such as effective salvage therapy or hematopoietic stem cell transplantation or who refuse these options at the time of enrollment. * Detection of FLT3-ITD mutation or FLT3-ITD/TKD co-mutations in bone marrow and/or peripheral blood samples within 30 days prior to study enrollment. * For frontline cohort: Patients must be chemonaive, i.e. not have received any chemotherapy (except hydrea or 1-2 doses of ara-C for transient control of hyperleukocytosis) for AML or MDS. They may have received transfusions, hematopoietic growth factors or vitamins for an antecedent hematological disorder (AHD) or for AML. Temporary prior measures such as apheresis, all-trans-retinoic acid (ATRA), steroids or hydrea while diagnostic work-up is being performed are allowed and not counted as a prior salvage. Supportive care therapy for MDS (growth factors, transfusions) will not be considered as prior therapy for MDS/AML and these patients will be enrolled to the frontline cohort of the study if they are otherwise eligible. * For relapsed cohort: Patients who have received at least one prior therapy for AML or for MDS with \> 10% blasts will be eligible. Patients may have received up to 4 prior salvages for AML and/or MDS (defined by the IPSS classification). Prior therapy for AML or MDS will be counted as a prior salvage. Patients who receive MDS directed therapies considered not purely supportive such as HMAs, lenalidomide, investigational therapies, will be enrolled to the salvage cohort if they are otherwise eligible. * In the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of protocol therapy will be at least 2 weeks for cytotoxic agents or at least 5 half-lives for cytotoxic/noncytotoxic agents. The half-life for the therapy in question will be based on published pharmacokinetic literature (abstracts, manuscripts, investigator brochure's, or drug-administration manuals) and will be documented in the protocol eligibility document * The use of chemotherapeutic or anti-leukemic agents is not permitted during the study with the following exceptions: (1) intratheca