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

Phase 1

Terminated

Conditions: Myelodysplastic Syndromes
Leukemia, Myeloid, Acute

Interventions: Drug: Venetoclax
Drug: CC-95251
Drug: Azacitidine

Registration Number: NCT05168202

Lead Sponsor: Bristol-Myers Squibb

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 218

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CC-95251 + azacitidine	Azacitidine	-
CC-95251 + azacitidine + venetoclax	Venetoclax	-
CC-95251 monotherapy	CC-95251	-
CC-95251 + azacitidine	CC-95251	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With With Grade 3 or Higher Laboratory Abnormalities	From signing informed consent to 56 days post last dose (Approximately 30 months)	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.
Number of Participants With DLTs	From Cycle 1 Day 1 to Cycle 1 Day 28 up to 42 post first dose of cycle 1 (upto 42 days)	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.
Number of Participants With Treatment Emergent Adverse Events	From signing informed consent to 56 days post last dose (Approximately 30 months)	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.
Number of Participants With Clinically Significant ECG Abnormalities Presented as Adverse Events	From screening to 56 days post last dose (Approximately 29 months)	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.
Number of ECOG Evaluations With Shift of ECOG Score of 3 or Greater.	From screening to 56 days post last dose (Approximately 29 months)	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.
Number of Participants With Clinically Significant Changes in Vital Signs Presented as AEs	From signing informed consent to 56 days post last dose (Approximately 30 months)	Vital sign measurements include: Weight (kg), Temperature (°C), Systolic Blood Pressure (mmHg), Diastolic Blood Pressure (mmHg), Pulse (beats/min), Respiration Rate (breaths/min).

Secondary Outcome Measures

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

Trial Locations

Locations (32): Local Institution - 0030
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Los Angeles, California, United States
Local Institution - 0031
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Palo Alto, California, United States
Local Institution - 0047
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Miami, Florida, United States
Local Institution - 0001
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Houston, Texas, United States
Local Institution - 0027
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Wollongong, New South Wales, Australia
Local Institution - 0006
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Clayton, Victoria, Australia
Local Institution - 0005
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Heidelberg, Victoria, Australia
Local Institution - 0037
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Melbourne, Victoria, Australia
Local Institution - 0019
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Edmonton, Alberta, Canada
Local Institution - 0011
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Vancouver, British Columbia, Canada
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Local Institution - 0030
🇺🇸Los Angeles, California, United States