Study Stopped
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BMS-986253 in Myelodysplastic Syndromes
A Phase I/II Trial of BMS-986253 in Myelodysplastic Syndromes
2 other identifiers
interventional
2
1 country
1
Brief Summary
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....
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Nov 2022
Shorter than P25 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 4, 2021
CompletedFirst Posted
Study publicly available on registry
December 8, 2021
CompletedStudy Start
First participant enrolled
November 29, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 2, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
July 3, 2023
CompletedResults Posted
Study results publicly available
June 11, 2024
CompletedSeptember 30, 2025
September 1, 2025
2 months
December 4, 2021
February 13, 2024
September 11, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
Phase I: Optimal Biological Dose (OBD) for Human Humax (HuMax)-Interleukin 8 (IL-8) (BMS-986253)
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 levels below the lower limit of detection of the assay in real time by Ultrasensitive immunoassay based on Quanterix Simoa technology. The lower limit of quantification = 0.86 pg/mL by Myriad-Rules Based Medicine (RBM).
First 28 days (C1D28) on up to 30 days.
Phase I: Recommended Phase 2 Dose (RP2D) of Human Humax (HuMax)-Interleukin 8 (IL-8) (BMS-986253)
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 dose reduction or withdrawal.
First 28 days (C1D28)
Phase II: Overall Response Rate
Overall response rate (ORR= Complete Remission (CR) + Partial Remission (PR) + \[marrow CR + hematologic improvement (HI\]) of Human Humax (HuMax)-interleukin 8 (IL-8) (BMS-986253) with and without deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi) after 6 cycles of therapy was assessed by the 2006 International Working Group response criteria for Myelodysplastic Syndromes. Complete Remission (CR) is bone marrow ≤55% myeloblasts with normal maturation of all cell lines. Persistent dysplasia will be noted. Partial Remission (PR) is all CR criteria if abnormal before treatment except bone marrow blasts decreased by ≥50% over pretreatment but still \>5%. And cellularity and morphology not relevant.
6 months
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)
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 events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 if life-threatening. Grade 5 is death related to adverse event.
First 28 days and follow up after the end of the treatment cycle; approximately 2 months.
Phase II: Fraction of Participants With Clinical Response
Clinical response was assessed by the assessed by the 2006 International Working Group response criteria for Myelodysplastic Syndromes and reported with 95% confidence interval. Complete Remission (CR) is bone marrow ≤55% myeloblasts with normal maturation of all cell lines. Persistent dysplasia will be noted. Partial Remission (PR) is all CR criteria if abnormal before treatment except bone marrow blasts decreased by ≥50% over pretreatment but still \>5%. And cellularity and morphology not relevant. Stable disease is failure to achieve at least PR, but no evidence of progression for \>8 weeks. Progression is less than 5% blasts: ≥50% increase in blasts to \>5% blasts; 5%-10% blasts: ≥50% increase to 10% blasts; transfusion dependence. Relapse after CR or PR is at least 1 of the following: return to pre-treatment bone marrow blast percentage or decrement of ≥50% from maximum remission/response levels in granulocytes or platelets.
Study treatment until occurrence of disease progression, death, or unacceptable toxicity or until response assessment on Cycle 7 day 1 (C7D1), a maximum of 6 cycles
Secondary Outcomes (10)
Phase I: Area Under the Concentration Time Curve (AUC 0-24h) of Human Humax (HuMax)-Interleukin 8 (IL-8) (BMS-986253) in Myelodysplastic Syndromes (MDS) With and Without Deoxyribonucleic Acid (DNA) Methyltransferase Inhibitors (DNMTi)
Before infusion, within 30 minutes, start of infusion, 1, 4, 12, and 24 hours after end of infusion.
Phase I: Half-life of Human Humax (HuMax)-Interleukin 8 (IL-8) (BMS-986253) With and Without Deoxyribonucleic Acid (DNA) Methyltransferase Inhibitors (DNMTi)
Before infusion, within 30 minutes, start of infusion, 1, 4, 12, and 24 hours after end of infusion.
Phase I: Concentration of Human Humax (HuMax)-Interleukin 8 (IL-8) (BMS-986253) at Steady State With and Without Deoxyribonucleic Acid (DNA) Methyltransferase Inhibitors (DNMTi)
Before infusion, within 30 minutes, start of infusion, 1, 4, 12, and 24 hours after end of infusion.
Phase II: 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)
1 year
Phase II: Cytogenetic Response Rate
Study treatment until occurrence of disease progression, death, or unacceptable toxicity or until response assessment on Cycle 7 day 1 (C7D1), a maximum of 6 cycles
- +5 more secondary outcomes
Other Outcomes (2)
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
From first study intervention, study day 1, through study day 100 after the end of the treatment cycle; approximately 7 months.
Phase I: Proportion of Participants With Dose-limiting Toxicities (DLT)
First 28 days
Study Arms (4)
Phase I Eligible Higher Risk (HR) Myelodysplastic Syndromes (MDS) Participants
EXPERIMENTALEscalating doses of Human Humax (HuMax)-interleukin 8 (IL-8) (BMS-986253) + deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi) for higher risk (HR) myelodysplastic syndromes (MDS) participants.
Phase I Lower Risk (LR) Myelodysplastic Syndromes (MDS) Participants
EXPERIMENTALEscalating doses of Human Humax (HuMax)-interleukin 8 (IL-8) (BMS-986253) for lower risk (LR) myelodysplastic syndromes (MDS) participants.
Phase II Higher Risk (HR) Myelodysplastic Syndromes (MDS) Participants
EXPERIMENTALPhase II dose of Human Humax (HuMax)-interleukin 8 (IL-8) (BMS-986253) + deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi) for higher risk (HR) myelodysplastic syndromes (MDS) participants.
Phase II Lower Risk (LR) Myelodysplastic Syndromes (MDS) Participants
EXPERIMENTALPhase II dose of Human Humax (HuMax)-interleukin 8 (IL-8) (BMS-986253) for lower risk (LR) myelodysplastic syndromes (MDS) participants.
Interventions
For Higher Risk (HR) Myelodysplastic Syndromes (MDS) cohort, the study drug of BMS-986253 will be given in combination with standard of care (SOC) Food and Drug Administration (FDA)-approved DNMTi by mouth (PO) decitabine and cedazuridine according to guidelines outlined in FDA product label. Standard of care (SOC) DNMTi will be administered via oral route once daily starting Day (D)2 of each treatment cycle through D6.
For Higher Risk (HR) Myelodysplastic Syndromes (MDS) cohort, the study drug of BMS-986253 will be given in combination with standard of care (SOC) Food and Drug Administration (FDA)-approved DNMTi by mouth (PO) decitabine and cedazuridine according to guidelines outlined in FDA product label. Standard of care (SOC) DNMTi will be administered via oral route once daily starting Day (D)2 of each treatment cycle through D6.
Intravenous (IV) infusion, 200 mg/Vial (20 mg/mL) or 1000 mg/vial (100mg/mL). Abbreviated Title: Human Humax (HuMax)-interleukin 8 (IL-8) (BMS-986253) in Myelodysplastic Syndromes 34 Version Date: 9/08/2021 outlined in Food and Drug Administration (FDA) product label.
Bone marrow biopsy: required at screening/baseline, Phase I post cycle (C) 1(C1Day(D)28 +/- 3 days) and Phase II post cycle 2 (C2D28 +/- 3 days) and post cycle 6 (C6D28 +/- 3days); and if needed clinically in the setting of aplasia or concern for disease progression.
Bone marrow aspiration: required at screening/baseline, Phase I post cycle (C) 1(C1Day(D)28 +/- 3 days) and Phase II post cycle 2 (C2D28 +/- 3 days) and post cycle 6 (C6D28 +/- 3days); and if needed clinically in the setting of aplasia or concern for disease progression.
12-lead electrocardiogram (ECGs) will be performed at baseline only for safety.
Eligibility Criteria
You may qualify if:
- Participants must have histologically or cytologically confirmed myelodysplastic syndromes (MDS) according to 2016 World Health Organization (WHO) criteria
- And:
- have higher-risk myelodysplastic syndrome (HR-MDS) Revised International Prognostic Scoring System (R-IPSS \>= 3.5) and received a minimum of 2 and maximum of 8 prior cycles for phase I and 4 for phase II of deoxyribonucleic acid (DNA) methyltransferase inhibitors (DNMTi) therapy, or
- have lower-risk myelodysplastic syndrome (LR-MDS) (R-IPSS \<3.5),
- and, at least one cytopenia:
- granulocytes \< 1.0 x 10\^9/L and/or
- hemoglobin \< 110 g/L with signs/symptoms of symptomatic anemia or transfusion-dependency
- platelets \< 100 x 10\^9/L
- Age \>=18 years
- Because no dosing or adverse event data are currently available on the use of HuMax-interleukin 8 (IL-8) BMS-986253 as monotherapy or in combination with DNMTi in participants \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
- Eastern Cooperative Oncology Group (ECOG) performance status \<=2 (Karnofsky \>=60%).
- Life expectancy greater than 6 months.
- Participants must have adequate organ function as defined below:
- total bilirubin \<=1.5 X institutional upper limit of normal OR \<=3 X institutional upper limit of normal in participants with Gilbert's syndrome (\*except for participants with increased bilirubin levels attributed to intramedullary hemolysis, which will be allowable)
- Aspartate aminotransferase (AST)/Serum glutamic oxaloacetic transaminase (SGOT)/Alanine transaminase (ALT)/Serum glutamic-pyruvic transaminase (SGPT) \<=3 X institutional upper limit of normal OR \<=5 X institutional upper limit of normal if related to disease specific cause
- +3 more criteria
You may not qualify if:
- For phase I: Participants with HR-MDS (R-IPSS \>=3.5) that have not yet received or received less than 2 cycles of DNMTi therapy.
- Participants with LR-MDS (R-IPSS \<3.5) with the following characteristics that have not yet received or are still deriving benefit from the following standard of care therapies:
- Hemoglobin (Hgb) \<10 g/dL, Epo level \<500 mU/mL: Erythropoietin-stimulating agents (ESAs)
- MDS with del5q: Lenalidomide
- MDS with ringed sideroblasts (MDS-RS) with splicing factor 3b subunit 1 (SF3B1) mutation: Luspatercept
- Participants with platelet transfusion-refractory thrombocytopenia, with inability to keep platelet threshold above 10K/mcL with transfusions or those with ongoing or uncontrolled hemorrhagic complications.
- Participants with clinically significant neutropenia, absolute neutrophil count (ANC)\<100, with frequent hospitalizations for infection (average \>1 hospitalization per month in past 6 months)
- Participants who are receiving or have received any other investigational agents within 28 days before start of study
- treatment.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to DNMTi or other agents used in study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women or women presently breast-feeding their children are excluded due to unknown risks to a developing fetus or infant.
- Any significant disease that, in the opinion of the investigator, may impair the participant s tolerance of study treatment.
- Active or uncontrolled autoimmune diseases requiring treatment.
- Chronic hepatitis B or C infection, because potential immune impairment caused by these disorders may diminish the effectiveness of this immunologic therapy.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Najla El Jurdi
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Najla El Jurdi, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
December 4, 2021
First Posted
December 8, 2021
Study Start
November 29, 2022
Primary Completion
February 2, 2023
Study Completion
July 3, 2023
Last Updated
September 30, 2025
Results First Posted
June 11, 2024
Record last verified: 2025-09
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data from this study may be requested from other researchers after the completion of the primary endpoint. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
- Access Criteria
- Data from this study may be requested by contacting the principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
All collected individual participant data (IPD) will be shared. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).