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

NCT05168202 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: CA059-0012021-002799-38
• Study Type: interventional
• Target: 56
• Locations: 9 countries
• Sites: 32

Brief Summary

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.

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Keywords

Myelodysplastic Syndromes; Acute Myeloid Leukemia; AML; MDS; Hematologic Cancers; Leukemia; Anti-SIRPa antibody; CC-95251

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (5)

• Cmax

  On Cycle 1 Day 1, C1D22 and C2D22.

• Tmax

  On Cycle 1 Day 1, C1D22 and C2D22.

• AUC(0-T)

  On Cycle 1 Day 1, C1D22 and C2D22.

• AUC(TAU)

  On Cycle 1 Day 1, C1D22 and C2D22.

• Cmin

  On Cycle 1 Day 1, C1D22 and C2D22.

Study Arms (3)

CC-95251 monotherapy

EXPERIMENTAL

Drug: CC-95251

CC-95251 + azacitidine

EXPERIMENTAL

Drug: CC-95251; Drug: Azacitidine

CC-95251 + azacitidine + venetoclax

EXPERIMENTAL

Drug: Venetoclax

Interventions

CC-95251 DRUG

Specified dose on specified days

Also known as: BMS-986351

CC-95251 + azacitidine; CC-95251 monotherapy

Azacitidine DRUG

Specified dose on specified days

CC-95251 + azacitidine

Venetoclax DRUG

Specified dose on specified days

CC-95251 + azacitidine + venetoclax

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (32)

Local Institution - 0030

Los Angeles, California, 90095, United States

Location

Local Institution - 0031

Palo Alto, California, 94304, United States

Location

Local Institution - 0047

Miami, Florida, 33136, United States

Location

Local Institution - 0001

Houston, Texas, 77030, United States

Location

Local Institution - 0027

Wollongong, New South Wales, 2500, Australia

Location

Local Institution - 0006

Clayton, Victoria, 3168, Australia

Location

Local Institution - 0005

Heidelberg, Victoria, 3084, Australia

Location

Local Institution - 0037

Melbourne, Victoria, 3065, Australia

Location

Local Institution - 0019

Edmonton, Alberta, T6G 2B7, Canada

Location

Local Institution - 0011

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Local Institution - 0010

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution - 0038

Montreal, Quebec, H3T 1E2, Canada

Location

Local Institution - 0040

Marseille, 13009, France

Location

Local Institution - 0029

Nantes, 44000, France

Location

Local Institution - 0020

Pessac, 33600, France

Location

Local Institution - 0023

Toulouse, 31059, France

Location

Local Institution - 0041

Villejuif, 94805, France

Location

Local Institution - 0018

Meldola, Emilia-Romagna, 47014, Italy

Location

Local Institution - 0026

Milan, 20162, Italy

Location

Local Institution - 0017

Rozzano, 20089, Italy

Location

Local Institution - 0025

Bergen, 5021, Norway

Location

Local Institution - 0013

Oslo, N-0027, Norway

Location

Local Institution - 0032

Badalona, Barcelona [Barcelona], 08916, Spain

Location

Local Institution - 0039

Barcelona, 08041, Spain

Location

Local Institution - 0036

Madrid, 28007, Spain

Location

Local Institution - 0035

Salamanca, 37007, Spain

Location

Local Institution - 0028

Santander, 39008, Spain

Location

Local Institution - 0021

Gothenburg, 413 45, Sweden

Location

Local Institution - 0015

Lund, 22185, Sweden

Location

Local Institution - 0014

Stockholm, 141 86, Sweden

Location

Local Institution - 0044

Edinburgh, Midlothian, EH4 2XU, United Kingdom

Location

Local Institution - 0050

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia

Interventions

Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Due to a strategic re-evaluation and prioritization of the company's portfolio, this study was terminated early during dose escalation (Part A) and prior to the start of dose expansion (Parts B, C, and D) with no relation to any safety issues associated with the use of CC-95251. Due to this termination, secondary efficacy endpoints, which were for these dose expansion cohorts, were not presented.

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

1-855-907-3286

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2021
• First Posted: December 23, 2021
• Study Start: January 19, 2022
• Primary Completion: July 30, 2024
• Study Completion: July 30, 2024
• Last Updated: September 25, 2025
• Results First Posted: September 25, 2025

Record last verified: 2025-09

Locations

AU (4); US (4); IT (3); FR (5); ES (5); NO (2); CA (4); SE (3); GB (2)