A Study to Assess the Effect of CC-95251 in Participants With Acute Myeloid Leukemia and Myelodysplastic Syndromes

A Phase 1, Open-label, Dose Finding Study of CC-95251 Alone and in Combination With Antineoplastic Agents in Subjects With Acute Myeloid Leukemia and Myelodysplastic Syndromes

The purpose of this study is to evaluate the safety, tolerability, and preliminary clinical activity of CC-95251 alone and in combination with antineoplastic agents in participants with relapsed or refractory acute myeloid leukemia and relapsed or refractory and treatment-naive higher risk melodysplastic syndromes.

Study Overview

• Status: Terminated
• Conditions: Myelodysplastic Syndromes; Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: CC-95251; Drug: Venetoclax; Drug: Azacitidine

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Wollongong, New South Wales, Australia, 2500
      • Local Institution - 0027
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Local Institution - 0006
    • Heidelberg, Victoria, Australia, 3084
      • Local Institution - 0005
    • Melbourne, Victoria, Australia, 3065
      • Local Institution - 0037
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Local Institution - 0019
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Local Institution - 0011
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 0010
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Local Institution - 0038
• France
  • Marseille, France, 13009
    • Local Institution - 0040
  • Nantes, France, 44000
    • Local Institution - 0029
  • Pessac, France, 33600
    • Local Institution - 0020
  • Toulouse, France, 31059
    • Local Institution - 0023
  • Villejuif, France, 94805
    • Local Institution - 0041
• Italy
  • Milan, Italy, 20162
    • Local Institution - 0026
  • Rozzano, Italy, 20089
    • Local Institution - 0017
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • Local Institution - 0018
• Norway
  • Bergen, Norway, 5021
    • Local Institution - 0025
  • Oslo, Norway, N-0027
    • Local Institution - 0013
• Spain
  • Barcelona, Spain, 08041
    • Local Institution - 0039
  • Madrid, Spain, 28007
    • Local Institution - 0036
  • Salamanca, Spain, 37007
    • Local Institution - 0035
  • Santander, Spain, 39008
    • Local Institution - 0028
  • Barcelona [Barcelona]
    • Badalona, Barcelona [Barcelona], Spain, 08916
      • Local Institution - 0032
• Sweden
  • Gothenburg, Sweden, 413 45
    • Local Institution - 0021
  • Lund, Sweden, 22185
    • Local Institution - 0015
  • Stockholm, Sweden, 141 86
    • Local Institution - 0014
• United Kingdom
  • Midlothian
    • Edinburgh, Midlothian, United Kingdom, EH4 2XU
      • Local Institution - 0044
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7LE
      • Local Institution - 0050
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Local Institution - 0030
    • Palo Alto, California, United States, 94304
      • Local Institution - 0031
  • Florida
    • Miami, Florida, United States, 33136
      • Local Institution - 0047
  • Texas
    • Houston, Texas, United States, 77030
      • Local Institution - 0001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group Performance Status of 0 to 2

For Parts A & B:

• Relapsed or refractory (R/R) acute myeloid leukemia (AML) as defined by the 2016 WHO Classification
• R/R myelodysplastic syndromes (MDS) as defined by the 2016 WHO Classification with intermediate, high or very high risk by Revised International Prognostic Scoring System (IPSS-R)

For Part C:

• Treatment-naïve (TN) (ie, previously untreated) MDS as defined by the 2016 WHO Classification with intermediate, high or very high risk by IPSS-R

For Part D:

• TN AML as defined by the 2016 WHO Classification, including secondary AML and therapy-related AML in participants who are ineligible (IE) for intensive chemotherapy (IC) and allogeneic hematopoietic stem cell transplant (HSCT)

Exclusion Criteria:

• Acute promyelocytic leukemia
• Immediately life-threatening, severe complications of leukemia such as disseminated/uncontrolled infection, uncontrolled bleeding, and/or uncontrolled disseminated intravascular coagulation
• Participants who have received prior treatment with a CD47 or SIRPα targeting agent
• Participant is on chronic systemic immunosuppressive therapy or corticosteroids
• Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half-lives or 4 weeks prior to starting study treatment, whichever is shorter (relapsed or refractory participants only).
• Any condition including, active or uncontrolled infection, or the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study
• Pregnant or nursing participants.

Other protocol-defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CC-95251 monotherapy	Drug: CC-95251; Specified dose on specified days; Other Names: BMS-986351
Experimental: CC-95251 + azacitidine	Drug: CC-95251; Specified dose on specified days; Other Names: BMS-986351; Drug: Azacitidine; Specified dose on specified days
Experimental: CC-95251 + azacitidine + venetoclax	Drug: Venetoclax; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With DLTs	A dose-limiting toxicity (DLT) is any treatment-related toxicity during Cycle 1 (Days 1-28, up to 42) not clearly due to illness or external causes. DLTs include: Any Grade ≥3 non-hematologic toxicity, except specific reversible or manageable cases (e.g., IRR, nausea, diarrhea, fatigue, infection with leukemia, TLS, electrolyte imbalance, liver enzyme elevations, or rash).; Any confirmed Hy's law case (ALT/AST ≥3× ULN + bilirubin >2× ULN without cholestasis).; Hematologic toxicities: Grade 4 neutropenia/thrombocytopenia persisting at Day 28 without active AML/MDS; febrile neutropenia or Grade ≥3 thrombocytopenia with severe bleeding and prolonged myelosuppression (>42 days) without active leukemia.; Any adverse event requiring dose reduction in Cycle 1 unless clearly unrelated to the drug.	From Cycle 1 Day 1 to Cycle 1 Day 28 up to 42 post first dose of cycle 1 (upto 42 days)
Number of Participants With Treatment Emergent Adverse Events	An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre-existing condition) should be considered an AE.	From signing informed consent to 56 days post last dose (Approximately 30 months)
Number of Participants With With Grade 3 or Higher Laboratory Abnormalities	Clinical laboratory values from laboratories will be graded according to CTCAE Version 5 for applicable tests programmatically. For laboratory values that fall outside of the grade criteria of CTCAE Version 5, a Grade of 0 will be assigned. In addition, normal ranges will be used to determine the categories of High, Low, and Normal for laboratory tests that have no severity grade.	From signing informed consent to 56 days post last dose (Approximately 30 months)
Number of Participants With Clinically Significant ECG Abnormalities Presented as Adverse Events	A single ECG will be performed in Screening, Cycle 1 Day 1 and 15, and Day 1 of Cycles ≥ 2. Investigators will make immediate clinical decisions based on their interpretation of the ECG results and provide their overall assessment.	From screening to 56 days post last dose (Approximately 29 months)
Number of ECOG Evaluations With Shift of ECOG Score of 3 or Greater.	ECOG Scale was used to assess performance status. Grades: 0: Fully active, able to carry on all pre-disease performance without estriction. 1: Restricted in physically strenuous activity but ambulatory, able to carry out work of light nature. 2: Ambulatory, capable of self-care, unable to carry out work activities. Up and about more than 50% waking hours. 3: Capable of limited self-care, confined to bed/chair more than 50% waking hours. 4: Completely disabled. Cannot carry on any self-care. Totally confined to bed/chair. 5: Dead. Baseline value was defined as the last non-missing value on or before the day that first dose of study drug is administered; if multiple values are present for the same date, the average of these values will be used as the baseline.	From screening to 56 days post last dose (Approximately 29 months)
Number of Participants With Clinically Significant Changes in Vital Signs Presented as AEs	Vital sign measurements include: Weight (kg), Temperature (°C), Systolic Blood Pressure (mmHg), Diastolic Blood Pressure (mmHg), Pulse (beats/min), Respiration Rate (breaths/min).	From signing informed consent to 56 days post last dose (Approximately 30 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum plasma concentration of drug	On Cycle 1 Day 1, C1D22 and C2D22.
Tmax	Time to maximum plasma concentration (Tmax)	On Cycle 1 Day 1, C1D22 and C2D22.
AUC(0-T)	Area under the plasma concentration time-curve up to the last measurable concentration (AUC0-t)	On Cycle 1 Day 1, C1D22 and C2D22.
AUC(TAU)	Area under the plasma concentration time-curve during a dosing interval (AUCtau)	On Cycle 1 Day 1, C1D22 and C2D22.
Cmin	Minimum serum concentration	On Cycle 1 Day 1, C1D22 and C2D22.

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2022
• Primary Completion (Actual): July 30, 2024
• Study Completion (Actual): July 30, 2024

Study Registration Dates

• First Submitted: December 8, 2021
• First Submitted That Met QC Criteria: December 8, 2021
• First Posted (Actual): December 23, 2021

Study Record Updates

• Last Update Posted (Estimated): September 25, 2025
• Last Update Submitted That Met QC Criteria: September 5, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; AML; Leukemia; MDS; Myelodysplastic Syndromes; Hematologic Cancers; CC-95251; Anti-SIRPa antibody
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Leukemia; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; venetoclax
• Other Study ID Numbers: CA059-001; 2021-002799-38 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No