Acute Myeloid LeukemiaPhase 1NCT04964505
Uproleselan, Azacitidine, and Venetoclax for the Treatment of Treatment Naive Acute Myeloid Leukemia
A Phase 1 study testing Azacitidine, Uproleselan and Venetoclax in people with Acute Myeloid Leukemia, run by Brian Jonas at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Azacitidine, Uproleselan and Venetoclax
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jul 2021to 7 Oct 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to understand and the willingness to sign a written informed consent
- Diagnosis of AML by World Health Organization (WHO) 2016 criteria (Arber 2016)
- Age >= 18 years
- Treatment naive and eligible for venetoclax plus hypomethylating agents (HMA)
- Age >= 75 OR
- Age 18-74 with at least one of the following co-morbidities:
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- Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3
- Cardiac history of congestive heart failure (CHF) requiring treatment or left ventricular ejection fraction (LVEF) =< 50% or chronic stable angina
- Carbon monoxide diffusing capability test (DLCO) =< 65% or forced expiratory volume in 1 second (FEV1) =< 65%
- Any other situation that the investigator judges to be incompatible with intensive chemotherapy must be reviewed with the study chair before study enrollment
- ECOG performance status of:
- 0 to 2 for subjects >= 75 years of age OR
- 0 to 3 for subjects 18-74 years of age
- White blood cell (WBC) =< 25,000/mm^3 at the start of study therapy (leukapheresis and hydroxyurea are allowed to meet this criteria). No other hematologic parameters
- Total bilirubin =< 1.5 x institution's upper limit of normal (ULN) unless related to AML or Gilbert's syndrome
- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum pyruvic glutamic transaminase (SPGT) =< 3 x institutional ULN unless related to AML
- Creatinine clearance >= 45 mL/min (calculated by the Cockcroft Gault formula or measured by 24-hour urine collection)
- Note, if >= 65 years of age, creatinine clearance or serum creatinine can be used for determining eligibility with creatinine clearance >= 45 mL/min (calculated by the Cockcroft Gault formula or measured by 24-hour urine collection) or serum creatinine =< institution's ULN considered eligible
- Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (non-estrogen hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman or female partner of a male subject become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
- Women of child-bearing potential has negative pregnancy test prior to initiating study drug dosing
- Able to swallow and retain oral medication
Who cannot join
- Current or anticipated use of other investigational agents
- Diagnosis of acute promyelocytic leukemia
- Active central nervous system involvement by AML
- AML must be treatment naive. Prior treatment with hypomethylating agent (azacitidine or decitabine), venetoclax or uproleselan, including for antecedent hematologic disorders. Prior allogeneic hematopoietic transplant for antecedent hematologic disorder is allowed if done at least 3 months prior to enrollment and there is no evidence of active graft versus host disease (GVHD) or requirement for systemic immune suppression
- Anticancer therapies, including investigational therapy, chemotherapy, targeted small molecule agents, or radiotherapy within 14 days or 5 half-lives (whichever is shorter) prior to the first dose and throughout venetoclax administration. Biologic agents (e.g. monoclonal antibodies) given for anti-neoplastic intent within 30 days prior to the first dose and throughout venetoclax administration
- Known diagnosis of human immunodeficiency virus (HIV) infection or known active hepatitis A, B or C infection with the exception of those with an undetectable viral load within 3 months of starting study treatment
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- Known strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment
- Subject has consumed grapefruit, grapefruit products, Seville oranges or Starfruit within 3 days prior to the initiation of study treatment
- Severe or uncontrolled medical disorder that would, in the investigator's opinion, impair ability to receive study treatment (i.e., uncontrolled diabetes, chronic renal disease, chronic pulmonary disease or active, uncontrolled infection, psychiatric illness/social situations that would limit compliance with study requirements)
- History of other malignancies, except for malignancy treated with curative intent with no known active disease present for >= 1 year; treated non-melanoma skin cancer; and localized, cured prostate and cervical cancer
- Evidence of uncontrolled active systemic infection requiring therapy (viral, bacterial, or fungal). Fever of unknown origin is not an exclusion criterion, as this may be disease related
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study
- Subject has a malabsorption syndrome of other condition that precludes enteral route of administration
- Subjects with a cardiovascular disability status of New York Heart Association class greater than 2
- Pregnant or nursing. There is a potential for congenital abnormalities and for this regimen to harm nursing infants.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
About this study
Official title: 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
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Azacitidine, Uproleselan, Venetoclax
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC
Given IV or SC
UproleselanDrug
Also called GMI-1271
Given IV
VenetoclaxDrug
Also called ABT-0199, ABT-199, ABT199, GDC-0199
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (uproleselan, azacitidine, venetoclax) | Experimental | 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. Receives: Drug: Azacitidine; Drug: Uproleselan; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Defined and graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 toxicity criteria.
Measured: Up to 30 days
Recommended phase II dose
Defined as the highest uproleselan dose level tested in which < 33% of patients experienced a dose limiting toxicity.
Measured: Up to end of cycle 1 (1 cycle = 28 days)
Secondary outcomes (8)
Rate of multiparameter flow cytometry (MFC) measurable/minimal residual disease (MRD) negative complete remission (CR) plus CR with incomplete count recovery (CRi)
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.
Measured: Up to 3 years
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.
Measured: Up to 3 years
Overall response rate (ORR)
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.
Measured: Up to 3 years
Rate of transfusion-independence (TI)
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.
Measured: Up to 3 years
Duration of CR/CRi and CR/CRh (DoR)
Analysis of DOR will be performed using Cox Regression, and Kaplan-Meier plots will be provided.
Measured: From the date of CR, CRi or CRh until the date of relapse or death, assessed up to 3 years
Relapse-free survival (RFS)
Analysis of RFS will be performed using Cox Regression, and Kaplan-Meier plots will be provided.
Measured: From the date of CR, CRi or CRh until the date of relapse or death from any cause, assessed up to 3 years
Event-free survival (EFS)
Analysis of EFS will be performed using Cox Regression, and Kaplan-Meier plots will be provided.
Measured: From the date of entry into study to the date of treatment failure, relapse, or death from any cause, assessed up to 3 years
Overall survival (OS)
Analysis of OS will be performed using Cox Regression, and Kaplan-Meier plots will be provided.
Measured: From the date of entry into study to the date of death from any cause, assessed up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2021
- Study start2 Jul 2021
- Primary completion4 Oct 2024
- Study completion7 Oct 2025
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brian Jonas
- Sponsor type
- University, hospital or other
- Collaborators
- GlycoMimetics Incorporated, National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Brian Jonas, University of California, Davis
- Investigators
- Brian A Jonas, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04964505
- Sponsor's protocol ID
- UCDCC#294
- Other IDs
- NCI-2021-06216, UCDCC#294, P30CA093373
- Status last verified
- Feb 2026
- First submitted
- 7 Jul 2021
- Last updated
- 23 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04964505
- Acronym / sponsor ID
- UCDCC#294
- Conditions
- Acute Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Brian JonasUniversity, hospital or other
- Collaborators
- GlycoMimetics Incorporated, National Cancer Institute (NCI)
- Study start
- 2 Jul 2021 (actual)
- Primary completion
- 4 Oct 2024 (actual)
- Study completion
- 7 Oct 2025 (actual)
- First posted
- 16 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (uproleselan, azacitidine, venetoclax) | Experimental | Drug: Azacitidine, Drug: Uproleselan, Drug: VenetoclaxPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Ability to understand and the willingness to sign a written informed consent
- Diagnosis of AML by World Health Organization (WHO) 2016 criteria (Arber 2016)
- Age >= 18 years
- Treatment naive and eligible for venetoclax plus hypomethylating agents (HMA)
- ECOG performance status of:
Key exclusion criteria (15 listed)
- Current or anticipated use of other investigational agents
- Diagnosis of acute promyelocytic leukemia
- Active central nervous system involvement by AML
- AML must be treatment naive. Prior treatment with hypomethylating agent (azacitidine or decitabine), venetoclax or uproleselan, including for antecedent hematologic disorders. Prior allogeneic hematopoietic transplant for antecedent hematologic disorder is allowed if done at least 3 months prior to enrollment and there is no evidence of active graft versus host disease (GVHD) or requirement for systemic immune suppression
- Anticancer therapies, including investigational therapy, chemotherapy, targeted small molecule agents, or radiotherapy within 14 days or 5 half-lives (whichever is shorter) prior to the first dose and throughout venetoclax administration. Biologic agents (e.g. monoclonal antibodies) given for anti-neoplastic intent within 30 days prior to the first dose and throughout venetoclax administration
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzacitidineAlso: 5 AZC, 5-AC, 5-Azacytidine, 5-AZCGiven IV or SC | Drug | Treatment (uproleselan, azacitidine, venetoclax) |
| UproleselanAlso: GMI-1271Given IV | Drug | Treatment (uproleselan, azacitidine, venetoclax) |
| VenetoclaxAlso: ABT-0199, ABT-199, ABT199, GDC-0199Given PO | Drug | Treatment (uproleselan, azacitidine, venetoclax) |
Primary outcome
Incidence of adverse events
Time frame: Up to 30 days
Defined and graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 toxicity criteria.
Recommended phase II dose
Time frame: Up to end of cycle 1 (1 cycle = 28 days)
Defined as the highest uproleselan dose level tested in which < 33% of patients experienced a dose limiting toxicity.
8 secondary outcomes
Rate of multiparameter flow cytometry (MFC) measurable/minimal residual disease (MRD) negative complete remission (CR) plus CR with incomplete count recovery (CRi)
Time frame: Up to 3 years
Rate of CR plus CR with partial count recovery (CRh)
Time frame: Up to 3 years
Overall response rate (ORR)
Time frame: Up to 3 years
Rate of transfusion-independence (TI)
Time frame: Up to 3 years
Duration of CR/CRi and CR/CRh (DoR)
Time frame: From the date of CR, CRi or CRh until the date of relapse or death, assessed up to 3 years
Relapse-free survival (RFS)
Time frame: From the date of CR, CRi or CRh until the date of relapse or death from any cause, assessed up to 3 years
Event-free survival (EFS)
Time frame: From the date of entry into study to the date of treatment failure, relapse, or death from any cause, assessed up to 3 years
Overall survival (OS)
Time frame: From the date of entry into study to the date of death from any cause, assessed up to 3 years
Results and safety
The study was stopped early (reason given: Sponsor decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian A Jonas principal investigator
University of California, Davis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Azacitidine, Uproleselan and Venetoclax in people with Acute Myeloid Leukemia, run by Brian Jonas at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (time frame: Up to 30 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2026.