What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML) include chemotherapy and targeted therapies such as midostaurin, venetoclax, and gemtuzumab. Chemotherapy side effects often include neutropenia, anemia, thrombocytopenia, nausea, vomiting, and hair loss. Targeted therapies can have additional side effects; for instance, midostaurin may cause gastrointestinal symptoms and elevated liver enzymes, venetoclax can lead to tumor lysis syndrome, and gemtuzumab is associated with liver toxicity and infusion-related reactions. The combination of Uproleselan with chemotherapy aims to mitigate some of these side effects, particularly reducing chemotherapy-induced damage to the bone marrow.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Acute Myeloid Leukemia (AML), including venetoclax, midostaurin, CPX-351, gemtuzumab ozogamicin, glasdegib, enasidenib, and ivosidenib. These drugs target various pathways and mechanisms involved in AML. For instance, venetoclax is a BCL-2 inhibitor, while midostaurin targets FLT3 mutations. Gemtuzumab ozogamicin is an antibody-drug conjugate targeting CD33. Although Uproleselan (an E-selectin antagonist) is not yet approved, it represents a novel approach by targeting the adhesion of leukemic cells to the bone marrow microenvironment, potentially enhancing the efficacy of chemotherapy.

What other types of research exist?

Promising novel alternatives to Uproleselan for AML patients include: 1) CD123-targeted therapeutic peptide loaded by micellar delivery system (mPO-6), which has shown efficacy in prolonging survival in refractory AML mice models by targeting the CD123/IL-3 axis. 2) HMA (hypomethylating agents) combined with venetoclax or ivosidenib, which have demonstrated benefits over HMA monotherapy in clinical settings.

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E-selectin Antagonist

Uproleselan + Chemotherapy for Acute Myeloid Leukemia

Phase 3

Waitlist Available

Led By Daniel J DeAngelo, MD, PhD

Research Sponsored by GlycoMimetics Incorporated

Eligibility Criteria Checklist

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

Must have

≥18 years and ≤75 years in age

No more than one prior stem cell transplant

Must not have

Prior use of G-CSF, CM-CSF or plerixafor within 7 days of dosing

Patients with acute promyelocytic leukemia, acute leukemia of ambiguous lineage (biphenotypic leukemia), chronic myeloid leukemia with myeloid blast crisis, or secondary refractory AML

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 5 years

Awards & highlights

Pivotal Trial

Summary

This trial is testing whether a drug called uproleselan can make chemotherapy more effective for patients with a type of blood cancer that has come back or not responded to treatment. Uproleselan works by blocking a protein that helps cancer cells hide in the bone marrow.

Who is the study for?

Adults aged 18-75 with relapsed or refractory Acute Myeloid Leukemia (AML) who haven't had more than one stem cell transplant and are medically eligible for chemotherapy. Excluded are those with recent use of certain growth factors, immunotherapy, radiotherapy, or chemotherapy; inadequate organ function; active hepatitis or HIV; moderate kidney dysfunction; uncontrolled infections; major surgery within the last month; specific types of leukemia other than AML.

What is being tested?

The trial is testing Uproleselan (GMI-1271), an E-selectin antagonist drug, combined with standard chemotherapy against a placebo plus chemotherapy in patients with relapsed/refractory AML. The goal is to see if Uproleselan improves treatment outcomes compared to the usual approach.

What are the potential side effects?

Possible side effects include reactions at the infusion site, changes in blood counts leading to increased risk of infection or bleeding, nausea and vomiting from chemotherapy, liver function abnormalities, fatigue and potential allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 18 and 75 years old.

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I have had only one stem cell transplant.

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My AML cancer has returned or is not responding to treatment.

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I have not received the specific chemotherapy planned for this trial before.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't used G-CSF, GM-CSF, or plerixafor in the last 7 days.

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My leukemia is one of the specific types not eligible for this trial.

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My cancer is affecting my brain or spinal cord.

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I haven't had immunotherapy, radiotherapy, or any experimental treatments in the last 28 days.

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My kidneys are not working well.

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I do not have an active hepatitis A, B, C, or HIV infection.

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I do not have any severe, uncontrolled infections.

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I have not had major surgery in the last 4 weeks.

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I have a serious heart condition.

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My organs are not functioning properly.

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My liver isn't working properly.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 5 years for reporting.

Treatment Details

Study Objectives

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

Secondary study objectives

Overall response rate

Rate of severe oral mucositis

Other study objectives

Adverse events

Duration of remission

Event-free survival

+2 more

Side effects data

From 2022 Phase 2 trial • 51 Patients • NCT04682405

100%

Neutrophil count decreased

100%

Platelet count decreased

100%

Diarrhea

100%

White blood cell decreased

100%

Hypocalcemia

96%

Nausea

96%

Anemia

92%

Lymphocyte count decreased

88%

Fatigue

88%

Hypoalbuminemia

81%

Abdominal Pain

81%

INR increased

81%

Hypophosphatemia

69%

Hypokalemia

65%

Vomiting

50%

Esophageal Pain

50%

Mucositis oral

38%

Esophagitis

35%

Constipation

35%

Enterocolitis

35%

Fever

35%

Malaise

31%

Hyponatremia

31%

Hypotension

27%

Thrush

23%

Gastritis

23%

Dizziness

19%

Hemorrhoids

19%

Back Pain

15%

Edema Limbs

15%

Anorexia

15%

Proctitis

12%

Skin Infection

12%

Activated partial thromboplastin time prolonged

12%

Gastroesophageal Reflux Disease

12%

Eye Disorders - other

12%

Infections and Infestations - other

12%

Enterocolitis Infectious

12%

Alanine aminotransferase increased

12%

Blood bilirubin increased

12%

Dehydration

12%

Hyperglycemia

12%

Musculoskeletal and Connective Tissue Disorder - other

Skin and Subcutaneous Tissue Disorders - other

Flatulence

Bruising

Creatinine increased

Aspartate aminotransferase increased

Wheezing

Generalized Muscle Weakness

Pain in Extremity

Periorbital Edema

Febrile neutropenia

Bloating

Infusion Site Extravasation

Hypernatremia

Hyperphosphatemia

Hypoglycemia

Headache

Peripheral Sensory Neuropathy

Anxiety

Dyspnea

Respiratory, Thoracic, and Mediastinal Disorders - other

Neoplasms benign, malignant, and unspecified (incl cysts and polyps) - other

Alkaline phosphatase increased

Hypertension

Sepsis

Fall

Papulopustular Rash

Dysphagia

Facial Pain

Urinary Tract Infection

Sinusitis

Vision Decreased

Bacteremia

Lung Infection

Sinus Tachycardia

Adrenal Insufficiency

Dry Mouth

Blurred Vision

Extraocular Muscle Paresis

Localized Edema

Chills

Toothache

Generalized Edema

Non-cardiac Chest Pain

Otitis Externa

Hyperkalemia

Muscle Cramp

Nervous System Disorders - other

Encephalopathy

Lethargy

Psychiatric Disorders - other

Testicular Pain

Confusion

Delirium

Hallucinations

Insomnia

Restlessness

Dysuria

Hematuria

Allergic Rhinitis

Cough

Nasal Congestion

Pulmonary Edema

100%

80%

60%

40%

20%

Study treatment Arm

Uproleselan + Standard of Care Melphalan

Placebo + Standard of Care Melphalan

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Uproleselan (GMI-1271)Experimental Treatment1 Intervention

Uproleselan in combination with mitoxantrone, etoposide and cytarabine (MEC) or fludarabine, cytarabine and idarubicin (FAI)

Group II: Placebo (Saline, 0.9% Sodium Chloride)Placebo Group1 Intervention

Placebo in combination with mitoxantrone, etoposide and cytarabine (MEC) or fludarabine, cytarabine and idarubicin (FAI)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Uproleselan

2021

Completed Phase 2

~100

0 / 15Eligibility criteria met

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

The most common treatments for Acute Myeloid Leukemia (AML) include chemotherapy, targeted therapies, and novel agents like E-selectin antagonists. Chemotherapy, such as cytarabine and daunorubicin, works by killing rapidly dividing cancer cells, but it also affects normal cells, leading to significant side effects. Targeted therapies, like FLT3 inhibitors, specifically target genetic mutations in AML cells, offering a more precise approach with potentially fewer side effects. Novel agents like uproleselan, an E-selectin antagonist, disrupt the interaction between AML cells and the bone marrow microenvironment, which is crucial for the survival and chemoresistance of leukemia cells. This mechanism is particularly important as it aims to enhance the efficacy of chemotherapy and reduce relapse rates, offering hope for improved outcomes in AML patients.

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.Molecular targeting in acute myeloid leukemia.