Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Venetoclax

Azacitidine

Antimetabolites

Enzyme Inhibitors

Patients receive uproleselan IV over 1 hour Q12H on days 1-7, azacitidine IV or SC QD on days 1-7, and venetoclax PO QD on days 1-28. Beginning cycle 5, patients achieving MLFS or better response, may receive azacitidine IV or SC QD and uproleselan IV over 1 hour QD on days 1-6 and 8 or days 1-5 and 8-9 or days 1-5. Treatment with uproleselan repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Cycles with azacitidine and venetoclax repeat every 28 days in the absence of disease progression and unacceptable toxicity.

Uproleselan

Brian A. Jonas

Brian A Jonas

This phase I trial evaluates the side effects of uproleselan, azacitidine, and venetoclax in treating older or unfit patients with treatment naive acute myeloid leukemia. Uproleselan may help block the formation of growths that may become cancer. Chemotherapy drugs, such as azacitidine, 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. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving uproleselan with azacitidine and venetoclax may help kill more cancer cells.

PRIMARY OBJECTIVE:

I. To assess the safety and tolerability of uproleselan combined with azacitidine and venetoclax in older or unfit patients with treatment naive acute myeloid leukemia (AML).

SECONDARY OBJECTIVE:

I. To evaluate the preliminary efficacy of uproleselan combined with azacitidine and venetoclax in older or unfit patients with treatment naive AML.

OUTLINE:

Patients receive uproleselan intravenously (IV) over 1 hour every 12 hours (Q12H) on days 1-7, azacitidine IV or subcutaneously (SC) once daily (QD) on days 1-7, and venetoclax orally (PO) QD on days 1-28. Beginning cycle 5, patients achieving morphologic leukemia-free state (MLFS) or better response, may receive azacitidine IV or SC QD and uproleselan IV over 1 hour QD on days 1-6 and 8 or days 1-5 and 8-9 or days 1-5. Treatment with uproleselan repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Cycles with azacitidine and venetoclax repeat every 28 days in the absence of disease progression and unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, and then every 3 months for 1 year.

Uproleselan, Azacitidine, and Venetoclax for the Treatment of Treatment Naive Acute Myeloid Leukemia

A Phase I Study of Uproleselan Combined With Azacitidine and Venetoclax for the Treatment of Older or Unfit Patients With Treatment Naive Acute Myeloid Leukemia

Defined and graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 toxicity criteria.

Defined as the highest uproleselan dose level tested in which \< 33% of patients experienced a dose limiting toxicity.

Will be summarized using means, medians, and percentiles for continuous variables and percentages for categorical variables and associated exact 95% confidence intervals will be constructed. Comparisons between subsets of study participants will be conducted using exact tests.

Defined as the rate of CR plus CRi and rate of CR plus CR with partial count recovery (CRh). Will be summarized using means, medians, and percentiles for continuous variables and percentages for categorical variables and associated exact 95% confidence intervals will be constructed. Comparisons between subsets of study participants will be conducted using exact tests.

Analysis of DOR will be performed using Cox Regression, and Kaplan-Meier plots will be provided.

Analysis of RFS will be performed using Cox Regression, and Kaplan-Meier plots will be provided.

Analysis of EFS will be performed using Cox Regression, and Kaplan-Meier plots will be provided.

Analysis of OS will be performed using Cox Regression, and Kaplan-Meier plots will be provided.

GlycoMimetics Incorporated

National Cancer Institute (NCI)

Brian Jonas

Principal Investigator

Heart and Blood Diseases

Immune System Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Melphalan

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

* On the evening of Day -3, patients will receive dose #1 of uproleselan
* On the following morning of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #2 of uproleselan
* On the evening of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #3 of uproleselan
* On Day -2 following completion of dose #3 of uproleselan, the patient will be administered the conditioning dose of melphalan (200mg/m\^2) as per institutional practice.
* On the following morning of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #4 of uproleselan
* On the evening of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #5 of uproleselan
* On the following morning of Day 0 (12 +/- 2 hours from prior dose) patients will receive dose #6 (final dose) of uproleselan
* On Day 0, 4 hours (+/- 2 hours) after the final dose of uproleselan, the patient will be infused with the HSC product. The patient will remain inpatient until engraftment

* On the evening of Day -3, patients will receive dose #1 of placebo
* On the following morning of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #2 of placebo On the evening of Day -2 (12 +/- 2 hours from prior dose), patients will receive dose #3 of placebo.
* On Day -2 following completion of dose #3 of placebo, the patient will be administered the conditioning dose of melphalan (200mg/m\^2) as per institutional practice.
* On the following morning of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #4 of placebo.
* On the evening of Day -1 (12 +/- 2 hours from prior dose), patients will receive dose #5 of placebo.
* On the following morning of Day 0 (12 +/- 2 hours from prior dose) patients will receive dose #6 (final dose) of placebo.
* On Day 0, 4 hours (+/- 2 hours) after the final dose of placebo, the patient will be infused with the HSC product. The patient will remain inpatient until engraftment

Placebo

Keith Stockerl-Goldstein, M.D.

The investigators hypothesize that prophylactic E-selectin inhibition via administration of uproleselan during melphalan conditioning will reduce the gastrointestinal (GI) toxicity in multiple myeloma (MM) patients undergoing auto-transplant, as assessed via diarrhea severity scoring per CTCAE v5.0, while potentially increasing chemosensitivity of malignant MM cells to high-dose melphalan.

Uproleselan (GMI-1271) for GI Toxicity Prophylaxis During Melphalan-Conditioned Autologous Hematopoietic Cell Transplantation (Auto-HCT) for Multiple Myeloma (MM)

A Phase II Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Uproleselan (GMI-1271) for GI Toxicity Prophylaxis During Melphalan-Conditioned Autologous Hematopoietic Cell Transplantation (Auto-HCT) for Multiple Myeloma (MM)

Grade 0 is defined as no diarrhea, or no change from baseline. Grade 1 is defined as an increase of \<4 stools per day over baseline; mild increase in ostomy output compared to baseline. Grade 2 is defined as an increase of 4-6 stools per day over baseline; moderate increase in ostomy output compared to baseline; limiting instrumental ADL. Grade 3 is defined as an increase of \>=7 stools per day over baseline; hospitalization indicated; severe increase in ostomy output compared to baseline; limited self care ADL. Grade 4 is defined as life-threatening consequences; urgent intervention indicated. Grade 5 is defined as death.

Grade 0 oral mucositis is defined as no presence of mucositis. Grade 1 oral mucositis is defined as asymptomatic or mild symptoms; intervention not indicated. Grade 2 oral mucositis is defined as moderate pain or ulcer that does not interfere with oral intake; modified diet indicated. Grade 3 oral mucositis is defined as severe pain; interfering with oral intake. Grade 4 oral mucositis is defined as life-threatening consequences; urgent intervention indicated. Grade 5 oral mucositis is defined as death.

Grade 0 esophagitis is defined as no presence of esophagitis. Grade 1 esophagitis is defined as asymptomatic; clinical or diagnostic observations only; intervention not indicated. Grade 2 esophagitis is defined as symptomatic; altered GI function; limiting instrumental ADL. Grade 3 esophagitis is defined as severely altered GI function; TPN indicated; elective invasive intervention indicated; limiting self care ADL. Grade 4 esophagitis is defined as life-threatening consequences; urgent operative intervention indicated. Grade 5 esophagitis is defined as death.

Grade 0 gastritis is defined as no presence of esophagitis. Grade 1 gastritis is defined as asymptomatic; clinical or diagnostic observations only; intervention not indicated. Grade 2 gastritis is defined as symptomatic; altered GI function; medical intervention indicated. Grade 3 gastritis is defined as severely altered eating or gastric function; TPN or hospitalization indicated. Grade 4 gastritis is defined as life-threatening consequences; urgent operative intervention indicated. Grade 5 gastritis is defined as death.

Grade 0 esophageal pain is defined as no esophageal pain. Grade 1 esophageal pain is defined as mild pain. Grade 2 esophageal pain is defined as moderate pain; limiting instrumental ADL. Grade 3 esophageal pain is defined as severe pain; limiting self care ADL. There is no grade 4 or 5 esophageal pain defined in the CTCAE v5.0.

Grade 0 abdominal pain is defined as no abdominal pain. Grade 1 abdominal pain is defined as mild pain. Grade 2 abdominal pain is defined as moderate pain; limiting instrumental ADL. Grade 3 abdominal pain is defined as severe pain; limiting self care ADL. There is no grade 4 or 5 abdominal pain defined in the CTCAE v5.0.

Grade 0 nausea is defined as no nausea. Grade 1 nausea is defined as loss of appetite without alteration in eating habits. Grade 2 nausea is defined as oral intake decreased without significant weight loss, dehydration or malnutrition. Grade 3 nausea is defined as inadequate oral caloric or fluid intake; tube feeding, TPN, or hospitalization indicated. There is no grade 4 or 5 nausea defined in the CTCAE v5.0.

Grade 0 vomiting is defined as no vomiting. Grade 1 vomiting is defined as intervention not indicated. Grade 2 vomiting is defined as outpatient IV hydration; medical intervention indicated. Grade 3 vomiting is defined as tube feeding, TPN, or hospitalization indicated. Grade 4 vomiting is defined as life-threatening consequences. Grade 5 vomiting is defined as death.

Grade 0 enterocolitis is defined as no enterocolitis. Grade 1 enterocolitis is defined as asymptomatic; clinical or diagnostic observations only; intervention not indicated. Grade 2 enterocolitis is defined as abdominal pain; mucus or blood in stool. Grade 3 enterocolitis is defined as severe or persistent abdominal pain; fever; ileus; peritoneal signs. Grade 4 enterocolitis is defined as life-threatening consequences; urgent intervention indicated. Grade 5 enterocolitis is defined as death.

Grade 0 proctitis is defined as no proctitis. Grade 1 proctitis is defined as rectal discomfort, intervention not indicated. Grade 2 proctitis is defined as symptomatic (e.g., rectal discomfort, passing blood or mucus); medical intervention indicated; limiting instrumental ADL. Grade 3 proctitis is defined as severe symptoms; fecal urgency or stool incontinence; limiting self-care ADL. Grade 4 proctitis is defined as life-threatening consequences; urgent intervention indicated. Grade 5 proctitis is defined as death.

Grade 0 hemorrhoids is defined as no hemorrhoids. Grade 1 hemorrhoids is defined as asymptomatic; clinical or diagnostic observations only; intervention not indicated. Grade 2 hemorrhoids is defined as symptomatic; banding or medical intervention indicated. Grade 3 hemorrhoids is defined as severe symptoms; invasive intervention indicated. There is no grade 4 or 5 hemorrhoids defined in the CTCAE v5.0.

-Defined as ANC ≥0.5 x 10\^9/L for 3 consecutive days or ≥1.0 x 10\^9/L for 1 day

Change in Bristol Stool Scale as measured by incidence of Type 7 Bristol Stool Scale: liquid consistency with no solid pieces.

Patient standing weight in kilograms was taken at specific time points to assess any changes in nutritional status.

Measured by the time in days to the first antibiotic dose for bacteremia.

This is defined as the number of doses of anti-diarrheal medications, such as loperamide or lomotil, that participants took daily.

The median daily dose of pain medications is provided as morphine equivalents.

* Questions regarding gastrointestinal toxicities
* Responses are scored from 1-5 with 1=no symptoms to 5=severe symptoms

* Questions regarding gastrointestinal, pain, and psychological symptoms interfering with daily activities
* Responses are scored from 1-5 with 1=not at all to 5=very much

* Questions regarding gastrointestinal toxicities
* Responses are scored from 1-5 with 1=never and 5=almost constantly

The Foundation for Barnes-Jewish Hospital

Washington University School of Medicine

Patients will receive six doses of Uproleselan intravenously. The doses will begin the evening of Day -3 and continue every 12 hours through the morning of Day 0, prior to hematopoietic stem cell transplant (auto-HCT). On the evening of Day -2, patients also receive one dose of standard of care Melphalan intravenously.

Uproleselan + Standard of Care Melphalan

Patients will receive six doses of placebo intravenously. The doses will begin the evening of Day -3 and continue every 12 hours through the morning of Day 0, prior to hematopoietic stem cell transplant (auto-HCT). On the evening of Day -2, patients also receive one dose of standard of care Melphalan intravenously.

Placebo + Standard of Care Melphalan

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Day -3

Day -2

Day -1

Day 0

Day 1

Day 2

Day 3

Day 4

Day 5

Day 6

Day 7

Day 8

Day 9

Day 10

Day 11

Day 12

Day 13

Day 14

The number of participants analyzed at each time point may differ from the overall number of participants analyzed because the data was not collected. One patient in the placebo + standard of care melphalan arm was not evaluable for the outcome measure.

Change in Diarrhea as Assessed Per CTCAE v5.0

Change in Oral Mucositis as Assessed Per CTCAE v5.0

Change in Esophagitis as Assessed Per CTCAE v5.0

Change in Gastritis as Assessed Per CTCAE v5.0

Change in Esophageal Pain as Assessed Per CTCAE v5.0

Change in Abdominal Pain as Assessed Per CTCAE v5.0

Change in Nausea as Assessed Per CTCAE v5.0

Change in Vomiting as Assessed Per CTCAE v5.0

Change in Enterocolitis as Assessed Per CTCAE v5.0

Change in Proctitis as Assessed Per CTCAE v5.0

Change in Hemorrhoids as Assessed Per CTCAE v5.0

One subject dropped out of Placebo + Standard of Care Melphalan arm due to adverse events and was not included in the analysis for this outcome measure.

Time to Neutrophil Engraftment

Change in Nutritional Status as Assessed by Total Parenteral Nutrition (TPN) Days

Duration of Hospital Length of Stay

Day -3, AM

Day -3, PM

Day -2, AM

Day -2, PM

Day -1, AM

Day -1, PM

Day 0, AM

Day 0, PM

Day 1, AM

Day 1, PM

Day 2, AM

Day 2, PM

Day 3, AM

Day 3, PM

Day 4, AM

Day 4, PM

Day 5, AM

Day 5, PM

Day 6, AM

Day 6, PM

Day 7, AM

Day 7, PM

Day 8, AM

Day 8, PM

Day 9, AM

Day 9, PM

Day 10, AM

Day 10, PM

Day 11, AM

Day 11, PM

Day 12, AM

Day 12, PM

Day 13, AM

Day 13, PM

Day 14, AM

Day 14, PM

Change in Bristol Stool Scale

Day 14 or day of discharge, whichever is sooner

Change in Nutritional Status as Assessed by Change in Standing Weight

Incidence of Infection Assessed by Rates of Bacteremia (With Organism Reported When Available)

Time to First Antibiotics

Incidence of Clostridium Difficile Infections

Median Daily Dose of Anti-diarrheal Medications

Median Daily Dose of Pain Medications

Severity of difficulty swallowing - Day -3

Severity of difficulty swallowing - Day 8

Severity of difficulty swallowing - date of discharge or Day 14 (whichever is sooner)

Severity of mouth or throat sores - Day -3

Severity of mouth or throat sores - Day 8

Severity of mouth or throat sores - date of discharge or Day 14 (whichever is sooner)

Severity of decreased appetite - Day -3

Severity of decreased appetite - Day 8

Severity of decreased appetite - date of discharge or Day 14 (whichever is sooner)

Severity of nausea - Day -3

Severity of nausea - Day 8

Severity of nausea - date of discharge or Day 14 (whichever is sooner)

Severity of vomiting - Day -3

Severity of vomiting - Day 8

Severity of vomiting - date of discharge or Day 14 (whichever is sooner)

Severity of heartburn - Day -3

Severity of heartburn - Day 8

Severity of heartburn - date of discharge or Day 14 (whichever is sooner)

Severity of bloating - Day -3

Severity of bloating - Day 8

Severity of bloating - date of discharge or Day 14 (whichever is sooner)

Severity of abdominal pain - Day -3

Severity of abdominal pain - Day 8

Severity of abdominal pain - date of discharge or Day 14 (whichever is sooner)

Median Change in Scores of Patient Reported Outcomes as Measured by the CTCAE Pro Form v1.0

Mouth or throat sore interference - Day -3

Mouth or throat sore interference - Day 8

Median Change in Scores of Quality of Life as Measured by the CTCAE Pro Form v 1.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Uproleselan, Azacitidine, and Venetoclax for the Treatment of Treatment Naive Acute Myeloid Leukemia	NCT04964505	Acute Myeloid L...	Azacitidine Uproleselan Venetoclax	18 Years -	University of California, Davis
Uproleselan (GMI-1271) for GI Toxicity Prophylaxis During Melphalan-Conditioned Autologous Hematopoietic Cell Transplantation (Auto-HCT) for Multiple Myeloma (MM)	NCT04682405	Multiple Myelom...	Uproleselan Placebo Melphalan	18 Years - 75 Years	Washington University School of Medicine
Uproleselan, Cladribine, and Low Dose Cytarabine for the Treatment of Patients With Treated Secondary Acute Myeloid Leukemia	NCT04848974	Secondary Acute...	Cladribine Cytarabine Uproleselan	18 Years -	M.D. Anderson Cancer Center
Study to Determine the Efficacy of Uproleselan (GMI-1271) in Combination With Chemotherapy to Treat Relapsed/Refractory Acute Myeloid Leukemia	NCT03616470	Acute Myeloid L...	Uproleselan Placebo	18 Years - 75 Years	GlycoMimetics Incorporated
Study to Determine the Efficacy of Uproleselan (GMI-1271) in Combination With Chemotherapy to Treat Relapsed/Refractory Acute Myeloid Leukemia	NCT03616470	Acute Myeloid L...	Uproleselan Placebo	18 Years - 75 Years	GlycoMimetics Incorporated
Uproleselan With Pre-Transplant Conditioning in Hematopoietic Stem Cell Transplantation for AML	NCT05569512	Acute Myeloid L... Pediatric Cance...	Uproleselan Fludarabine Clofarabine Busulfan	12 Months - 39 Years	Dana-Farber Cancer Institute
Daunorubicin and Cytarabine With or Without Uproleselan in Treating Older Adult Patients With Acute Myeloid Leukemia Receiving Intensive Induction Chemotherapy	NCT03701308	Acute Myeloid L...	Cytarabine Daunorubicin Uproleselan	60 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for uproleselan

Every month we try and update this database with for uproleselan cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for uproleselan

Every month we try and update this database with for uproleselan cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for uproleselan cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.