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This research study is studying a new drug, uproleselan, to see if it is safe and effective in decreasing relapse after stem cell transplant and improving leukemia-free survival in pediatric patients with acute myeloid leukemia (AML). The name of the study drugs involved in this study are: Uproleselan Busulfan Clofarabine Fludarabine Tacrolimus Methotrexate Mycophenolate Mofetil


Acute Myeloid Leukemia, Pediatric Cancer

Recruitment Status


Detailed Description

This is a single arm, multi-center, phase 1/2 trial involving the use of the study drug, uproleselan, as part of the pre stem cell transplant conditioning regimen for pediatric patients with acute myeloid leukemia (AML). This study is looking to learn what dose of uproleselan should be given and the safety of uproleselan when combined with other drugs as part of the pre stem cell transplant conditioning regimen. The U.S. Food and Drug Administration (FDA) has not approved uproleselan as a treatment for any disease. This is the first time that uproleselan will be given to children. Uproleselan is expected to treat acute myeloid leukemia (AML) by making AML cells sensitive to chemotherapy drugs that are part of standard of care pre-transplant conditioning regimen which could help make the transplant more effective..The standard of care conditioning regimen will include the drugs busulfan, clofarabine, and fludarabine. The standard of care drugs tacrolimus, and either methotrexate or mycophenolate mofetil will be used during the stem cell transplant course. The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. Participants will receive study drug doses for 7 days before their stem cell transplant and will be followed for 2 years following their stem cell transplant. It is expected that about 28 people will take part in this research study. GlycoMimetics, Inc., a pharmaceutical company, is supporting this research study by providing the study drug (uproleselan) and funding for some of the laboratory tests.

Eligibility Criteria

Inclusion Criteria:

Age ≥12 months and ≤ 30 years
Lansky/Karnofsky performance status ≥70% (see Appendix A)
Weight ≥10 kg

Acute myeloid leukemia that arises de novo or is secondary to:

cytotoxic chemoradiotherapy
myelodysplastic syndrome
a leukemia predisposition syndrome or inherited marrow failure syndrome other than ones associated with transplant-related morbidity and mortality. A predisposition resulting from a germline RUNX1 mutation is example of an eligible disorder. Fanconi Anemia and Dyskeratosis Congenita are examples of ineligible disorders.

Disease status: Multidimensional flow cytometry (MDF) to assess disease status for eligibility will be performed centrally by Hematologics.

In a first or second complete remission (defined as marrow with ≤1% leukemic blasts by MDF and no evidence of extramedullary disease) with minimal residual disease (MRD, defined as marrow with ≥0.05% leukemic blasts by MDF) after at least 2 cycles of induction/re-induction chemotherapy.
Have newly diagnosed disease or disease in first relapse that is refractory (defined as marrow with >1% leukemic blasts by MDF or persistence of extramedullary disease) to at least 2 cycles of induction/re-induction chemotherapy.

This sample will be used for eligibility as well as correlative biomarkers. Please see section 9.2 for details regarding collection, processing, and shipping of the sample.

Graft and Donor Types:

Patients must be receiving bone marrow or peripheral blood stem cells from a HLA identical related or HLA matched unrelated (allele level matched at A, B, C and DRB1 loci) donor.
Eligibility of prospective donors should be determined in compliance with requirements of 21 CFR Part 1271. This should include donor screening for COVID-19 exposure or infection.
Ability to understand and/or the willingness of their parent or legally authorized representative to sign a written informed consent document.

Exclusion Criteria:

Participants who have had a previous hematopoietic stem cell transplantation
Participants who have had prior treatment with uproleselan
CNS 3 disease at time of admission for HSCT. Patients previously diagnosed CNS 3 disease that has improved (CNS1 or CNS2) will be eligible. (See Section 3.3 for definitions).
Down Syndrome
Fanconi Anemia, Dyskeratosis Congenita and other disorders associated with excess risk for transplant related toxicities
Acute Promyelocytic Leukemia
Multiply relapsed (≥2) disease
Pregnancy (positive serum beta-HCG) or breastfeeding Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with uproleselan, breastfeeding should be discontinued if the mother is treated with uproleselan. These potential risks also apply to other agents used in this study.
Absolute neutrophil count <300/μL due to treatment (chemotherapy or immunotherapy).

Patients with neutropenia due to disease related marrow dysfunction (refractory disease, underlying myelodysplasia or an underlying marrow failure disorder) will be eligible regardless of the absolute neutrophil count. However, enrolling centers must provide clear evidence that the neutrophil count is not rising, that the patient does not have an inadequately controlled infection (see section 3.2.15), and that the patient is on broad anti-fungal prophylaxis. Given the serious risk associated with starting conditioning in patients with severe neutropenia, centers are encouraged to delay transplant if they have any reason to believe that the absolute neutrophil count may improve.

Estimated GFR of <60 mL/min/1.73 m2. Estimated GFR may be calculated using the CKD-EPI Creatinine Equation (2009) for patients ≥19 years or creatinine-based Bedside Schwartz equation (2009) for patients <19 years. It is recommended that estimates be determined using the calculators found on the National Kidney Foundation website. the ( Any patient for whom these equations yields a GFR less than 90 mL/min/1.73 m2 should have radionucleotide testing. Measurement of 24-hour urine creatinine clearance is not an acceptable substitute for radionucleotide testing.
Cardiac ejection fraction <50% or shortening fraction <27%
Total bilirubin (with elevated direct bilirubin) or ALT >2 X ULN.
Pulmonary disease with FVC, FEV1 or DLCO (corrected for hemoglobin) <50 % predicted or requiring supplemental oxygen. Children who are developmentally unable to perform pulmonary function testing will be assessed solely on their need for supplemental oxygen
Active hepatitis B or C infection
Active, poorly controlled infections. In patients being treated for infection at the time of enrollment, source documentation of the results of all microbiologic, radiographic and pathology assessments performed for diagnosis and for evaluation of response to treatment will be required.

Patients with a known history of HIV are excluded, unless they meet all of the following conditions:

No history of HIV complications with the exception of CD4 count <200 cells/mm3
No antiretroviral therapy with overlapping toxicity such as myelosuppression
CD4 count >500 cells/mm3 prior to the diagnosis of relapsed AML
HIV viral loads below the limit of detection
No history of highly active antiretroviral therapy (HAART)-resistant HIV
Patients who have received another investigational drug within 28 days or 5 half-lives (whichever is longer).


Intervention Type

Intervention Name










Phase 1, Phase 2



Min Age

12 Months

Max Age

30 Years

Download Date

June 23, 2023

Principal Investigator

John Horan, MD, MPH 

This field has been modified from to show a contact specific to Boston Children's.

Primary Contact Information

John Horan, MD, MPH

This field has been modified from to show a contact specific to Boston Children's.

For more information on this trial, visit


For more information and to contact the study team:

Uproleselan With Pre-Transplant Conditioning in Hematopoietic Stem Cell Transplantation for AML NCT05569512 John Horan, MD, MPH