Highest Dose of Uproleselan in Combination With Fludarabine and Cytarabine for Patients With Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Mixed Phenotype Acute Leukemia Relapsed or Refractory That Expresses E-selectin Ligand on the Cell Membrane
A Phase 1 and Pharmacokinetic Study of Uproleselan (GMI-1271, NSC #801708) in Combination With Fludarabine and Cytarabine for Patients With Acute Myeloid Leukemia, Myelodysplastic Syndrome or Mixed Phenotype Acute Leukemia That Expresses E-selectin Ligand on the Cell Membrane and is in Second or Greater Relapse or That is Refractory to Relapse Therapy
4 other identifiers
interventional
8
1 country
19
Brief Summary
This phase I trial tests the safety, side effects, and determination of the best dose of uproleselan in combination with fludarabine and cytarabine in treating patients with acute myeloid leukemia, myelodysplastic syndrome or mixed phenotype acute leukemia that has come back (relapsed) or does not respond to treatment (refractory) and that expresses E-selectin ligand on the cell membrane. Uproleselan binds to E-selectin expressed on endothelial cells of the bone marrow and prevents their interaction with selectin-E ligand-expressing cancer cells. This may prevent leukemia cells from being sequestered in the bone marrow niche and escaping the effect of chemotherapy. Chemotherapy drugs, such as fludarabine and cytarabine, 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 uproleselan in combination with fludarabine and cytarabine may expose more cancer cells to the effect of chemotherapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Oct 2023
Typical duration for phase_1
19 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 18, 2021
CompletedFirst Posted
Study publicly available on registry
December 7, 2021
CompletedStudy Start
First participant enrolled
October 10, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2025
CompletedResults Posted
Study results publicly available
May 5, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
May 9, 2026
ExpectedMay 5, 2026
November 1, 2025
1.5 years
November 18, 2021
March 12, 2026
April 15, 2026
Conditions
Outcome Measures
Primary Outcomes (6)
Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D) of Uproleselan
The MTD/RP2D will be the maximum dose at which fewer than one-third of patients experience dose limiting toxicities.
Up to 28 days
Cycle 1 Dose Limiting Toxicity of Uproleselan
The frequency (%) of patients who experience a dose limiting toxicity on cycle 1, stratified by study part and dose level.
Up to 28 days
Area Under the Plasma Concentration Versus Time Curve of Uproleselan
The median (min, max) of the area under the plasma concentration versus time curve of uproleselan will be assessed immediately pre-dose as well as 30 minutes, 1 hour, 2 hour, and 4-hours post-dose on day 1 and day 6 of cycle 1 for patients weighing at least 10kg. Patients less than 10kg will be assessed immediately pre-dose as well as 30 minutes, 1.5 hours, and 4-hours post-dose on day 1 and day 6 of cycle 1. Summary statistics will be stratified by study part and dose level.
Up to 6 days
Total Plasma Clearance of Uproleselan
The median (min, max) of the total plasma clearance of uproleselan will be assessed immediately pre-dose as well as 30 minutes, 1 hour, 2 hour, and 4-hours post-dose on day 1 and day 6 of cycle 1 for patients weighing at least 10kg. Patients less than 10kg will be assessed immediately pre-dose as well as 30 minutes, 1.5 hours, and 4-hours post-dose on day 1 and day 6 of cycle 1. Summary statistics will be stratified by study part and dose level.
Up to 6 days
Elimination Half-life of Uproleselan
The median (min, max) of the elimination half-life of uproleselan will be assessed immediately pre-dose as well as 30 minutes, 1 hour, 2 hour, and 4-hours post-dose on day 1 and day 6 of cycle 1 for patients weighing at least 10kg. Patients less than 10kg will be assessed immediately pre-dose as well as 30 minutes, 1.5 hours, and 4-hours post-dose on day 1 and day 6 of cycle 1. Summary statistics will be stratified by study part and dose level.
Up to 6 days
Maximum Concentration of Uproleselan
The median (min, max) of the maximum concentration of uproleselan will be assessed immediately pre-dose as well as 30 minutes, 1 hour, 2 hour, and 4-hours post-dose on day 1 and day 6 of cycle 1 for patients weighing at least 10kg. Patients less than 10kg will be assessed immediately pre-dose as well as 30 minutes, 1.5 hours, and 4-hours post-dose on day 1 and day 6 of cycle 1. Summary statistics will be stratified by study part and dose level.
Up to 6 days
Secondary Outcomes (2)
Expression of E-selectin Ligand on the Surface of Myeloid Leukemic Blasts of Uproleselan
Up to 28 days
Antileukemic Activity of Uproleselan
Up to 56 days
Other Outcomes (1)
Relative Reduction in Myeloid Leukemic Blast Percentage in Bone Marrow of Uproleselen
Up to 56 days
Study Arms (1)
Treatment (uproleselan, fludarabine, cytarabine)
EXPERIMENTALPatients receive uproleselan intravenously (IV) once daily (QD) over 20 minutes on day 1 and IV over 20 minutes twice daily (BID) on days 2-8, fludarabine IV QD over 30 minutes on days 2-6, and high dose cytarabine IV QD over 1-3 hours on days 2-6. Patients also receive cytarabine intrathecal therapy (IT) or intrathecal triple therapy (ITT) on day 0. CNS2 and CNS3 patients receive additional cytarabine IT or ITT once weekly starting on day 7-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with Down syndrome will receive leucovorin orally (PO) or IV BID following each intrathecal administration of methotrexate.
Interventions
Give PO or IV
Given IT
Given IV and IT
Eligibility Criteria
You may qualify if:
- Patient must be enrolled on APAL2020SC (NCT04726241)-Pediatric Acute Leukemia (PedAL) Screening Trial - Developing New Therapies for Relapsed Leukemias - A Leukemia \& Lymphoma Society and COG Groupwide Screening Protocol
- Patients must be \>= 1 year and \<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 with increased blasts (MDS-IB), therapy-related myelodysplastic syndrome with increased blasts (MDS-IB) 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) with increased blasts (MDS-IB).
- Second or greater relapse or refractory mixed phenotype acute leukemia (MPAL)
- Note: Documentation of E-selectin expression by multidimensional flow cytometry (MDF) at the central laboratory (Hematologics, Inc.) on the most recent bone marrow sample prior to the diagnosis of the current relapsed or refractory disease is acceptable for eligibility to this study in the event of isolated extramedullary disease, inability to obtain a bone marrow aspirate or lack of leukemic blasts in the peripheral blood
- Bone marrow relapse and MDF - MRD relapse: (patients must meet one of the following criteria to be defined as having relapse disease)
- A single bone marrow sample showing \>= 1% leukemic blasts by multidimensional flow cytometry performed at the central laboratory (performed only at Hematalogics through the screening study APAL2020SC).
- 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 and MDF - MRD refractory: Following a re-induction cycle after any relapse, presence of \>= 1% leukemic blasts by multidimensional flow cytometry performed at the central laboratory (performed only at Hematologics through the screening study APAL2020SC), OR there is persistent extramedullary disease. In cases where a bone marrow aspirate cannot be obtained because of extensive fibrosis, assessment of refractory disease will be defined as described
- 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 (grade \<2) 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, eg, blood count criteria, the patient is considered to have recovered adequately
- +24 more criteria
You may not qualify if:
- Patients with any of the following diagnoses
- Patients with isolated relapsed or refractory central nervous system (CNS) disease or isolated relapsed or refractory testicular disease
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Children's Oncology Groupcollaborator
- LLS PedAL LLCcollaborator
- National Cancer Institute (NCI)lead
Study Sites (19)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329, United States
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Results Reporting Coordinator
- Organization
- Children's Oncology Group
Study Officials
- PRINCIPAL INVESTIGATOR
Maria Luisa Sulis
Pediatric Early Phase Clinical Trial Network
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 18, 2021
First Posted
December 7, 2021
Study Start
October 10, 2023
Primary Completion
March 31, 2025
Study Completion (Estimated)
May 9, 2026
Last Updated
May 5, 2026
Results First Posted
May 5, 2026
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.