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

NCT04964505 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: UCDCC#294NCI-2021-06216P30CA093373
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events

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

  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.

  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)

  Up to 3 years

• Rate of CR plus CR with partial count recovery (CRh)

  Up to 3 years

• Overall response rate (ORR)

  Up to 3 years

• Rate of transfusion-independence (TI)

  Up to 3 years

• Duration of CR/CRi and CR/CRh (DoR)

  From the date of CR, CRi or CRh until the date of relapse or death, assessed up to 3 years

Study Arms (1)

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.

Drug: Azacitidine; Drug: Uproleselan; Drug: Venetoclax

Interventions

Uproleselan DRUG

Given IV

Also known as: GMI-1271

Treatment (uproleselan, azacitidine, venetoclax)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (uproleselan, azacitidine, venetoclax)

Azacitidine DRUG

Given IV or SC

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, Onureg, U-18496, Vidaza

Treatment (uproleselan, azacitidine, venetoclax)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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:
• to 2 for subjects \>= 75 years of age OR
• 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

You may not qualify if:

• 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
• 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
• 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.

Sponsors & Collaborators

• Brian Jonas: lead
• GlycoMimetics Incorporated: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; uproleselan; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Brian A Jonas

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 7, 2021
• First Posted: July 16, 2021
• Study Start: July 2, 2021
• Primary Completion: October 4, 2024
• Study Completion: October 7, 2025
• Last Updated: February 23, 2026

Record last verified: 2026-02

Locations

US (1)