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Study of BMS-986497 (ORM-6151) as a Monotherapy, in Double and Triple Combination With Azacitidine and Venetoclax in Participants With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

Phase 1
Recruiting
Conditions
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Interventions
Registration Number
NCT06419634
Lead Sponsor
Bristol-Myers Squibb
Brief Summary

The purpose of this study is to assess the safety, tolerability, drug levels, drug efficacy and determine the recommended dose of BMS-986497 as a monotherapy, in double combination with Azacitidine and in triple combination with Azacitidine and Venetoclax in participants with relapsed or refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
105
Inclusion Criteria
  • Adults with primary or secondary relapsed and/or refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
  • Detectable levels of cluster of differentiation 33 (CD33) expression.
  • Failed alternative therapies with established benefit.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2 and adequate organ function.
Exclusion Criteria
  • Acute Promyelocytic Leukemia.
  • Clinically active central nervous system leukemia.
  • Active malignant solid tumor.
  • Pregnant or breastfeeding.
  • Other protocol-defined inclusion/exclusion criteria apply.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Part 1: Dose Escalation BMS-986497 (Monotherapy)BMS-986497-
Part 2, Cohort A: Dose Expansion BMS-986497 (Combination Therapy)BMS-986497-
Part 2, Cohort A: Dose Expansion BMS-986497 (Combination Therapy)Azacitidine-
Part 2, Cohort B: Dose Expansion BMS-986497 (Triple Combination Therapy)BMS-986497-
Part 2, Cohort B: Dose Expansion BMS-986497 (Triple Combination Therapy)Azacitidine-
Part 2, Cohort B: Dose Expansion BMS-986497 (Triple Combination Therapy)Venetoclax-
Primary Outcome Measures
NameTimeMethod
Incidence of treatment-emergent adverse events (TEAEs)Up to 2 years
Determine the Recommended Phase 2 Dose (RP2D) of BMS-986497 as MonotherapyUp to 2 years
RP2D of BMS-986497 as Combination TherapyUp to 2 years

The combination therapy included BMS-986497 and Azacitidine

RP2D of BMS-986497 as Triple Combination TherapyUp to 2 years

The triple combination therapy included BMS-986497, Azacitidine and Venetoclax.

Incidence of dose-limiting toxicities (DLTs)Up to 21 days
Secondary Outcome Measures
NameTimeMethod
Best overall response (BOR)Up to 4 years
Complete remission (CR)Up to 4 years
Time to reach Cmax (Tmax)Up to 2 years
Area under the curve from time 0 to last quantifiable concentration (AUC0-last)Up to 2 years
Complete remission with incomplete hematologic recovery (Cri)Up to 4 years
Event-free survival (EFS)Up to 4 years
Transition rate to allogeneic hematopoietic stem cell transplantation (HSCT)Up to 4 years
Maximum concentration (Cmax)Up to 2 years
Overall response rate (ORR)Up to 4 years
Duration of response (DoR)Up to 4 years
Complete remission with partial hematologic recovery (CRh) rateUp to 4 years
Incidence of Anti-drug antibody (ADA) against BMS-986497Up to 2 years

Trial Locations

Locations (15)

Yale-New Haven Hospital

🇺🇸

New Haven, Connecticut, United States

Local Institution - 0010

🇺🇸

Chicago, Illinois, United States

Local Institution - 0007

🇺🇸

Boston, Massachusetts, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Washington University School of Medicine, Siteman Cancer Center

🇺🇸

Saint Louis, Missouri, United States

John Theurer Cancer Center at Hackensack University Medical Center

🇺🇸

Hackensack, New Jersey, United States

Columbia University Irving Medical Center

🇺🇸

New York, New York, United States

University of Texas MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Local Institution - 0009

🇺🇸

Fairfax, Virginia, United States

Princess Margaret Cancer Centre

🇨🇦

Toronto, Ontario, Canada

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Yale-New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Amer Zeidan, Site 0011
Contact
203-737-7078
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