Who can participate?

Inclusion Criteria:

• Patient must be enrolled on APAL2020SC (NCT04726241)
• Patients must be < 18 years of age at the time of study enrollment
• Patients, with or without Down syndrome (DS), and with de novo acute myeloid leukemia, therapy-related acute myeloid leukemia, myelodysplastic syndrome or mixed phenotype acute leukemia that expresses E-selectin ligand on the cell membrane according to APAL2020SC screening results and meet one of the following:
  • Second or greater relapse or refractory AML as defined below, including isolated extramedullary disease (EMD), but excluding isolated central nervous system (CNS) or isolated testicular disease
  • Second or greater relapse or refractory myelodysplastic syndrome (MDS)
  • Second or greater relapse or refractory mixed phenotype acute leukemia (MPAL)
• Bone marrow relapse: (patients must meet one of the following criteria to be defined as having relapse disease)
  
  • A single bone marrow sample showing >= 5% leukemic blasts by flow cytometry performed at the central laboratory, fluorescence in situ hybridization (FISH) testing or other molecular method
  • A single bone marrow with at least two tests showing >= 1% leukemic blasts; examples of tests include:
    • Flow cytometry showing leukemia >= 1% by multidimensional flow cytometry (MDF) performed at the central laboratory (performed at Hematologics Inc. through the screening study APAL2020SC)
    • Karyotypic abnormality with at least one metaphase similar or identical to diagnosis
    • FISH abnormality identical to one present at diagnosis
    • Polymerase chain reaction (PCR) or next generation sequencing (NGS)-based demonstration of leukemogenic lesion identical to diagnosis and >= 1%
  • In cases where a bone marrow aspirate cannot be obtained because of extensive fibrosis, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy. A complete blood count documenting the presence of at least 1,000/ uL (i.e., a white blood count [WBC] count >= 10,000/uL with >= 10% blasts or a WBC count of >= 5,000/uL with >= 20% blasts) circulating leukemic cells (blasts) can also be used if a bone marrow aspirate or biopsy cannot be performed
• Extramedullary relapse: Biopsy proven extramedullary disease after documented complete remission
• Refractory disease: Following a re-induction cycle after a second relapse, presence of ≥1% leukemic blasts by flow cytometry performed at the central laboratory (performed only at Hematologics through the screening study APAL2020SC), OR there is persistent extramedullary disease
• Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
• Karnofsky >= 50 for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age. Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
  • Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive:
    • >= 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea
    • NOTE: Cytoreduction with hydroxyurea must be discontinued >= 24 hours prior to the start of protocol therapy
  • Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent
  • Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
  • Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
  • Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (eg. pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
  • Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
  • Stem cell Infusions (with or without total-body irradiation [TBI]):
    • Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
    • Autologous stem cell infusion including boost infusion: >= 30 days
  • Cellular Therapy: >= 30 days after the completion of any type of cellular therapy (eg, modified T cells, natural killer [NK] cells, dendritic cells, etc.)
  • External beam radiation therapy (XRT)/External Beam Irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
  • Patients must not have received prior exposure to uproleselan (GMI-1271). NOTE: Prior therapy with fludarabine and/or cytarabine is permitted
• For patients with leukemia:
  • Platelet count >= 25,000/uL (may receive platelet transfusions)
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a creatinine based on age/gender as follows:
  • Age: 1 month to < 6 months; Maximum serum creatinine (mg/dL): 0.4 (male); 0.4 (female)
  • Age: 6 months to < 1 year; Maximum serum creatinine (mg/dL): 0.5 (male); 0.5 (female)
  • Age: 1 to < 2 years; Maximum serum creatinine (mg/dL): 0.6 (male); 0.6 (female)
  • Age: 2 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 (male); 0.8 (female)
  • Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 (male); 1 (female)
  • Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male); 1.2 (female)
  • Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female)
  • Age: >= 16 years; Maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female)
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 225 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L
• Albumin >= 2 g/dL
• Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by gated radionuclide study

Exclusion Criteria:

• Patients with any of the following diagnoses
  • Patients with isolated or refractory central nervous system (CNS) disease or isolated or refractory testicular relapse
  • Patients with acute promyelocytic leukemia (APL)
  • Patients with juvenile myelomonocytic leukemia (JMML)
  • Patients with a known congenital bone marrow failure syndrome
• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study and for 3 months after the last dose of uproleselan (GMI-1271). Abstinence is an acceptable method of birth control
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible except patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible