Phase 3 Study of Uproleselan Plus Chemo Fails to Improve Survival in R/R AML


A phase 3 study evaluating uproleselan in relapsed/refractory acute myeloid leukemia missed its primary end point of overall survival.

Photomicrograph of bone marrow aspirate showing myeloblasts of AML: © David A Litman -

Photomicrograph of bone marrow aspirate showing myeloblasts of AML: © David A Litman -

The combination of uproleselan (GMI-1271) plus chemotherapy did not lead to a statistically significant improvement in overall survival (OS) in patients with relapsed/refractory acute myeloid leukemia (R/R AML), missing the primary end point of a phase 3 study (NCT03616470) evaluating the agent.1

Patients in the uproleselan arm had a median OS of 13 months vs 12.3 months in the placebo arm. Regarding safety, adverse events were consistent with the known profile of chemotherapy.

“While the outcome of our phase 3 study in R/R AML is not what we hoped, we wish to thank the investigators, the participating patients and their families for their dedication to this large, well-controlled randomized study,” said Harout Semerjian, chief executive officer of GlycoMimetics, in a press release. “We are thoroughly analyzing the data in collaboration with medical, statistical and regulatory experts and are committed to submitting a comprehensive data analysis for presentation at an upcoming medical meeting.”

The phase 3, randomized, double-blind, placebo-controlled study investigated uproleselan or placebo with mitoxantrone, etoposide, and cytarabine or fludarabine, cytarabine, and idarubicin in 388 patients. Patients received placebo or uproleselan plus chemotherapy for 8 days for 1 induction cycle and up to 3 consolidation cycles.

In addition to the primary end point of OS, the study’s secondary end points included incidence of severe oral mucositis, complete remission rate, and remission rate.1,2

Findings from another trial, a phase 1/2 study (NCT02306291) of uproleselan plus conventional salvage chemotherapy, showed a complete response rate of 35% and a median OS of 8.8 months. Low rates of oral mucositis were also reported in this study. Further, no dose-limiting toxicities were observed among the first 19 patients included.3

An adaptive phase 2/3 study (NCT03701308) of uproleselan in newly diagnosed AML is being conducted by the National Cancer Institute and the Alliance for Clinical Trials in Oncology. This study includes patients who are 60 years or older and fit for intensive chemotherapy. Uproleselan will be added to a standard cytarabine/daunorubicin regiment and compared with chemotherapy alone. The phase 2 portion completed enrollment of 267 patients in December 2021, and the event-free survival analysis will be reported when data are available.1

1. GlycoMimetics announces results of pivotal phase 3 study of uproleselan in relapsed/refractory (R/R) acute myeloid leukemia (AML). News release. GlycoMimetics. May 6, 2024. Accessed May 7, 2024.
2. Study to determine the efficacy of uproleselan (GMI-1271) in combination with chemotherapy to treat relapsed/​refractory acute myeloid leukemia. Updated July 25, 2023. Accessed May 7, 2024.
3. DeAngelo DJ, Jonas BA, Liesveld JL, et al. Phase 1/2 study of uproleselan added to chemotherapy in patients with relapsed or refractory acute myeloid leukemia. Blood. 2022;139(8):1135-1146. doi:10.1182/blood.2021010721
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