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NCT05148234

BMS-986253 in Myelodysplastic Syndromes

Terminated Phase 1, PHASE2 Results posted Last updated 30 September 2025
What this trial tests

Phase 1, PHASE2 trial testing Deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi) Decitabine in Myelodysplastic Syndromes in 2 participants. Terminated before completion.

Timeline
29 November 2022
Primary endpoint
2 February 2023
3 July 2023

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment2
Start date29 November 2022
Primary completion2 February 2023
Estimated completion3 July 2023
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Myelodysplastic Syndromes. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Phase I: Optimal Biological Dose (OBD) for Human Humax (HuMax)-Interleukin 8 (IL-8) (BMS-986253) Primary · First 28 days (C1D28) on up to 30 days.

OBD of BMS-986253 with and without deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi), as determined by dose limiting toxicity (DLT) occurring by cycle 1 day 28 (C1D28). DLT is defined as any of the following: any grade ≥ non-hematologic toxicity that is possibly, probably, or definitely related to study drug. Liver injury as defined by a positive Hy's Law. And adverse reaction that leads to dose reduction or withdrawal. OBD is the lowest tolerated dose level showing optimal biological activity, defined as maximal suppression of serum free IL-8 levels. The goal is to achieve IL-8

With DNMTi
GroupValue95% CI
All ParticipantsNA
Without DNMTi
GroupValue95% CI
All ParticipantsNA
Phase I: Recommended Phase 2 Dose (RP2D) of Human Humax (HuMax)-Interleukin 8 (IL-8) (BMS-986253) Primary · First 28 days (C1D28)

RP2D of BMS-986253 with and without deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi), as determined by dose -limiting toxicity (DLT) occurring by cycle 1 day 28 (C1D28). RP2D is defined as the optimal biological dose expected to be safe and of potential efficacy. It serves as a starting point for further investigations in future phase 2 clinical trials. DLT is defined as any of the following: ang grade ≥ non-hematologic toxicity that is possibly, probably, or definitely related to study drug. Liver injury as defined by a positive Hy's Law. And adverse reaction that leads to dos

With DNMTi
GroupValue95% CI
All ParticipantsNA
Without DNMTi
GroupValue95% CI
All ParticipantsNA
Phase I: Number of Grades 1-5 Serious and/or Non-serious Adverse Events Related to Human Humax (HuMax)-Interleukin 8 (IL-8) (BMS-986253) and Deoxyribonucleic Acid (DNA) Methyltransferase Inhibitors (DNMTi) Primary · First 28 days and follow up after the end of the treatment cycle; approximately 2 months.

Safety as measured by incidence of adverse events (AEs) and serious adverse events (SAEs), and AEs leading to discontinuation, death, and laboratory abnormalities. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical even

Grades 1-5 Serious related to BMS-986253
GroupValue95% CI
Phase I Dose Level 1: 1200mg Eligible Higher Risk (HR) Myelodysplastic Syndromes (MDS) Participants0
Grades 1-5 Non-serious related to BMS-986253
GroupValue95% CI
Phase I Dose Level 1: 1200mg Eligible Higher Risk (HR) Myelodysplastic Syndromes (MDS) Participants0
Grade 1 -2 Serious related to DNMTi
GroupValue95% CI
Phase I Dose Level 1: 1200mg Eligible Higher Risk (HR) Myelodysplastic Syndromes (MDS) Participants0
Grade 3 Serious related to DNMTi - Febrile neutropenia
GroupValue95% CI
Phase I Dose Level 1: 1200mg Eligible Higher Risk (HR) Myelodysplastic Syndromes (MDS) Participants1
Grade 3 Serious related to DNMTi - Skin infection
GroupValue95% CI
Phase I Dose Level 1: 1200mg Eligible Higher Risk (HR) Myelodysplastic Syndromes (MDS) Participants1
Grade 2 Non-serious related to DNMTi - Lymphocyte count decreased
GroupValue95% CI
Phase I Dose Level 1: 1200mg Eligible Higher Risk (HR) Myelodysplastic Syndromes (MDS) Participants1
Grade 3 Non-serious related to DNMTi - White blood cell decreased
GroupValue95% CI
Phase I Dose Level 1: 1200mg Eligible Higher Risk (HR) Myelodysplastic Syndromes (MDS) Participants1
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) Secondary · From first study intervention, study day 1, through study day 100 after the end of the treatment cycle; approximately 7 months.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent

GroupValue95% CI
Phase I Dose Level 1: 1200mg Eligible Higher Risk (HR) Myelodysplastic Syndromes (MDS) Participants1
Phase I: Proportion of Participants With Dose-limiting Toxicities (DLT) Secondary · First 28 days

DLT is defined as any of the following: ang grade ≥ non-hematologic toxicity that is possibly, probably, or definitely related to study drug. Liver injury as defined by a positive Hy's Law. And adverse reaction that leads to dose reduction or withdrawal.

GroupValue95% CI
Phase I Dose Level 1: 1200mg Eligible Higher Risk (HR) Myelodysplastic Syndromes (MDS) Participants0

Adverse events — posted to ClinicalTrials.gov

Time frame: From first study intervention, study day 1, through study day 100 after after the end of the treatment cycle; approximately 7 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase I Dose Level 1: 1200mg Eligible Higher Risk (HR) Myelodysplastic Syndromes (MDS) Participants
Serious: 1/1 (100%)
Deaths: 0/1

Serious adverse events (3 terms)

ReactionSystemPhase I Dose Level 1: 1200…
Febrile neutropeniaBlood and lymphatic system disorders
Osteonecrosis of jawMusculoskeletal and connective tissue disorders
Skin infectionInfections and infestations
Other adverse events (3 terms — click to expand)

ReactionSystemPhase I Dose Level 1: 1200…
Lymphocyte count decreasedInvestigations
Neutrophil count decreasedInvestigations
White blood cell decreasedInvestigations

Most-reported serious reactions: Febrile neutropenia, Osteonecrosis of jaw, Skin infection.

Data from ClinicalTrials.gov NCT05148234 adverse events section.

Sponsor's own description

Background: The myelodysplastic syndromes (MDS) are a group of bone marrow neoplasms. MDS mostly affect elderly people. The drugs used to treat MDS are not always effective, and the only curative treatment is stem cell transplant. Researchers want to see if a new drug can be used to treat MDS. Objective: To learn if HuMax-interleukin 8 (IL-8) BMS-986253 is a safe and effective treatment for MDS. Eligibility: Adults aged 18 and older with MDS. Design: Participants will be screened with a medical history, medication review, and physical exam. They will answer questions about how well they are able to take care of themselves. Their temperature, blood pressure, breathing rate, and heart rate will be monitored. They will have an electrocardiogram to see how well their heart is working. They will give blood and urine samples. They may have a bone marrow biopsy. Participants will be assigned to a specific group. They will receive either BMS-986253 alone or in combination with deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi). Treatment will be given in 28-day cycles. Participants will get BMS-986253 as an infusion on days 1 and 15 of each cycle. Some participants also will take oral DNMTi on days 2-6 of each cycle. They will receive treatment until their disease gets worse or they have bad side effects. At study visits, some screening tests will be repeated. Some of the samples that are collected will be used for genetic testing. About 30 days after treatment ends, participants will have a follow-up visit to see how they are doing. After that, follow up will occur via phone every 3-6 months until the study ends. National Institutes of Health (NIH) will cover the costs for some travel expenses....

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention.
    Cambier S, Gouwy M, Proost P. · · 2023 · cited 387× · PMID 36725964 · DOI 10.1038/s41423-023-00974-6
  2. Emerging strategies in targeting tumor-resident myeloid cells for cancer immunotherapy.
    Wang Y, Johnson KCC, Gatti-Mays ME, Li Z. · · 2022 · cited 103× · PMID 36031601 · DOI 10.1186/s13045-022-01335-y
  3. CXCR2 chemokine receptor - a master regulator in cancer and physiology.
    Lazennec G, Rajarathnam K, Richmond A. · · 2024 · cited 53× · PMID 37872025 · DOI 10.1016/j.molmed.2023.09.003
  4. Role of innate immunological/inflammatory pathways in myelodysplastic syndromes and AML: a narrative review.
    Vegivinti CTR, Keesari PR, Veeraballi S, Martins Maia CMP, et al · · 2023 · cited 27× · PMID 37422676 · DOI 10.1186/s40164-023-00422-1
  5. Targeting DNA Methylation in Leukemia, Myelodysplastic Syndrome, and Lymphoma: A Potential Diagnostic, Prognostic, and Therapeutic Tool.
    Kalinkova L, Sevcikova A, Stevurkova V, Fridrichova I, et al · · 2022 · cited 19× · PMID 36614080 · DOI 10.3390/ijms24010633
  6. Targeting inflammation in lower-risk MDS.
    Gonzalez-Lugo JD, Verma A. · · 2022 · cited 14× · PMID 36485128 · DOI 10.1182/hematology.2022000350
  7. Clinical activity, pharmacokinetics, and pharmacodynamics of oral hypomethylating agents for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: A multidisciplinary review.
    Haumschild R, Kennerly-Shah J, Barbarotta L, Zeidan AM. · · 2024 · cited 12× · PMID 38509812 · DOI 10.1177/10781552241238979
  8. Immune dysregulation and potential targeted therapy in myelodysplastic syndrome.
    Zhang X, Yang X, Ma L, Zhang Y, et al · · 2023 · cited 11× · PMID 37547364 · DOI 10.1177/20406207231183330

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