What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML) often come with significant side effects. Hypomethylating agents (HMAs) like decitabine and azacitidine can cause myelosuppression, leading to neutropenia, anemia, and thrombocytopenia. Low-dose cytarabine (LoDAC) combined with venetoclax can also result in severe neutropenia and febrile neutropenia. Busulfan, clofarabine, and fludarabine, used in conditioning regimens for stem cell transplantation, are associated with myelosuppression, mucositis, and increased risk of infections. Additionally, ruxolitinib, used for symptom relief in myelofibrosis, can cause anemia and thrombocytopenia. These side effects necessitate careful monitoring and supportive care during treatment.

What prior FDA approvals exist?

Several drugs have been FDA-approved for the treatment of Acute Myeloid Leukemia (AML). Venetoclax, an orally available BCL2 inhibitor, is approved for use in combination with hypomethylating agents (HMAs) like azacitidine or decitabine. Ivosidenib, an IDH1 inhibitor, is approved for use in combination with azacitidine for newly diagnosed AML with IDH1 mutations. Other notable approvals include midostaurin for FLT3-mutated AML and enasidenib for IDH2-mutated AML. These treatments focus on targeting specific mutations and pathways involved in AML, similar to the investigational approach of E-selectin inhibition with Uproleselan.

What other types of research exist?

Promising novel alternatives to Uproleselan for AML patients include: 1) PO-6, a CD123-targeted therapeutic peptide delivered via a micellar system, which has shown efficacy in prolonging survival in refractory AML models by interfering with the CD123/IL-3 axis. 2) HMA (hypomethylating agents) combined with venetoclax or ivosidenib, which have demonstrated benefits over HMA monotherapy. 3) Azacitidine plus gilteritinib, which has shown a higher overall response rate compared to azacitidine plus placebo.

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E-selectin Inhibitor

Uproleselan for Acute Myeloid Leukemia

Phase 1

Waitlist Available

Led By John Horan

Research Sponsored by Malika Kapadia

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be younger than 65 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called uproleselan to see if it can help children with acute myeloid leukemia (AML) by making their cancer cells more sensitive to chemotherapy. The goal is to reduce relapse rates and improve survival after a stem cell transplant.

Who is the study for?

This trial is for pediatric AML patients aged 1 month to 30 years who have either newly diagnosed disease, are in first relapse, or have refractory disease after at least two chemotherapy cycles. They must be in remission with minimal residual disease and weigh over 10 kg. Participants need a compatible stem cell donor but can't join if they've had multiple relapses, certain organ dysfunctions, active infections including hepatitis B/C or HIV complications, previous stem cell transplants, Down Syndrome, or are pregnant/breastfeeding.

What is being tested?

The study tests uproleselan's safety and effectiveness when combined with pre-transplant conditioning drugs (busulfan, clofarabine, fludarabine) to reduce leukemia relapse and improve survival without leukemia post-stem cell transplant in children and young adults with AML.

What are the potential side effects?

Potential side effects of uproleselan may include reactions at the infusion site as well as general drug-related risks like nausea, vomiting, diarrhea. The conditioning drugs can cause mouth sores, low blood counts increasing infection risk; busulfan might also lead to liver issues.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Dose Limiting Toxicity (DLT) Phase 1

Dose Limiting Toxicity (DLT) Phase 2

Recommend Phase 2 Dose

Secondary study objectives

Leukemia

Number of Patients with Severe Oral or Gastrointestinal Mucositis

Overall Survival (OS)

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Uproleselan with pre-transplant conditioningExperimental Treatment4 Interventions

Participants will receive IV uproleselan on day -8 prior to stem cell transplant. Uproleselan will be administered IV twice daily from day -7 through day -2. Participants will also receive a standard pre-transplant conditioning regimen with fludarabine, clofarabine and busulfan. Each of these 3 drugs will be administered IV once daily from day -7 through day -4.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Uproleselan

2021

Completed Phase 2

~100

Clofarabine

2011

Completed Phase 3

~2530

Fludarabine

2012

Completed Phase 4

~1860

Busulfan

2008

Completed Phase 4

~1710

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Acute Myeloid Leukemia (AML) include intensive combination chemotherapy, which works by killing rapidly dividing cancer cells but also causes significant side effects like cytopenias and infections. Lower intensity treatments aim to reduce symptoms and prolong survival but are less likely to achieve long-term disease control. Specific agents like clofarabine and gilteritinib target particular pathways or mutations in AML cells, offering more tailored approaches. E-selectin inhibition, as seen with uproleselan, disrupts the adhesion of AML cells to the vascular niche, reducing chemoresistance and potentially improving treatment outcomes. Understanding these mechanisms helps tailor treatment plans to individual patient needs, improving efficacy and managing side effects.

Epigenetic deregulation in myeloid malignancies.Endothelial E-selectin inhibition improves acute myeloid leukaemia therapy by disrupting vascular niche-mediated chemoresistance.Progress in the problem of relapsed or refractory acute myeloid leukemia.