Study to Evaluate Safety and Tolerability of CC-91633 (BMS-986397) in Participants With Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes

A Phase 1, Open-label, Dose-finding Study of CC-91633 (BMS-986397) in Subjects With Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes

Study CC-91633-AML-001 is a Phase 1, open-label, dose escalation and expansion, first-in-human (FIH) clinical study of CC-91633 (BMS-986397) in participants with relapsed or refractory acute myeloid leukemia (R/R AML) or in participants with relapsed or refractory higher-risk myelodysplastic syndromes (R/R HR-MDS). The Dose Escalation part (Part A) of the study will enroll participants with R/R AML and R/R HR-MDS and will evaluate the safety and tolerability of escalating doses of CC-91633 (BMS-986397), administered orally, and determine the maximum tolerated dose (MTD) or preliminary recommended Phase 2 dose (RP2D) and schedule. Throughout the study, final decisions on dose escalation/de-escalation will be made by the safety review committee (SRC). Approximately 40 participants may be enrolled in Part A of the study.

The expansion part (Part B) will confirm tolerability of the selected doses and schedules and evaluate whether efficacy is in a range that warrants further clinical development. Separate expansion cohorts for participants with R/R AML and R/R HR-MDS may enroll approximately 20 to 40 response evaluable participants per cohort.

Parts A and B will consist of 3 periods: Screening, Treatment, and Follow-up.

Study Overview

• Status: Recruiting
• Conditions: Myelodysplastic Syndromes; Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: CC-91633

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: BMS Study Connect Contact Center www.BMSStudyConnect.com; Phone Number: 855-907-3286; Email: Clinical.Trials@bms.com
• Study Contact Backup: Name: First line of the email MUST contain NCT # and Site #.

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Not yet recruiting
      • Local Institution - 604
      • Contact: Site 604
    • Adelaide, South Australia, Australia, 5000
      • Withdrawn
      • Royal Adelaide Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Not yet recruiting
      • Monash Health
      • Contact: Jake Shortt, Site 602; Phone Number: +61395944044
    • Melbourne, Victoria, Australia, 3004
      • Not yet recruiting
      • The Alfred Hospital
      • Contact: Shaun Fleming, Site 601
    • Melbourne, Victoria, Australia, 3065
      • Not yet recruiting
      • Local Institution - 603
      • Contact: Site 603
    • Melbourne, Victoria, Australia, 3065
      • Withdrawn
      • St Vincent's Hospital
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Not yet recruiting
      • Local Institution - 203
      • Contact: Site 203
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Not yet recruiting
      • Local Institution - 201
      • Contact: Site 201
    • Toronto, Ontario, Canada, M5G 2M9
      • Not yet recruiting
      • Local Institution - 202
      • Contact: Site 202
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clínic de Barcelona
    • Contact: Jordi Esteve, Site 301
  • Barcelona, Spain, 08035
    • Recruiting
    • Vall d Hebron University Hospital
    • Contact: Olga Salamero, Site 302; Phone Number: +34932746000 00 00
  • Madrid, Spain, 28041
    • Recruiting
    • Local Institution - 303
    • Contact: Site 303
  • Sevilla, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen del Rocio
    • Contact: Eduardo Rodriguez Arboli, Site 304
• United Kingdom
  • Leeds, United Kingdom, LS9 7FT
    • Not yet recruiting
    • Local Institution - 503
    • Contact: Site 503
  • London, United Kingdom, W1T 7HA
    • Not yet recruiting
    • Local Institution - 505
    • Contact: Site 505
  • Oxford, United Kingdom, OX3 7LE
    • Not yet recruiting
    • Local Institution - 501
    • Contact: Site 501
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M20 4BX
      • Not yet recruiting
      • Local Institution - 504
      • Contact: Site 504
  • London, City Of
    • London, London, City Of, United Kingdom, SE5 9RL
      • Not yet recruiting
      • Local Institution - 502
      • Contact: Site 502
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Not yet recruiting
      • Local Institution - 111
      • Contact: Site 111
  • California
    • La Jolla, California, United States, 92093
      • Withdrawn
      • Local Institution - 103
  • Illinois
    • Chicago, Illinois, United States, 60611-5975
      • Withdrawn
      • Northwestern University School Of Medicine
    • Chicago, Illinois, United States, 60637
      • Not yet recruiting
      • Local Institution - 110
      • Contact: Site 110
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Andrew Brunner, Site 107
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
      • Contact: Daniel DeAngelo, Site 101; Phone Number: 617-632-3712
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington Univ School of Medicine Siteman Cancer Center
      • Contact: Geoffrey Uy, Site 105; Phone Number: 314-454-8304
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Withdrawn
      • Local Institution - 102
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Not yet recruiting
      • Local Institution - 108
      • Contact: Site 108
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas - MD Anderson Cancer Center
      • Contact: Courtney DiNardo, Site 104; Phone Number: 713-794-1141
  • Washington
    • Seattle, Washington, United States, 98104
      • Not yet recruiting
      • Local Institution - 109
      • Contact: Site 109

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Participants must satisfy the criteria below to be enrolled in the Dose Escalation (Part A) or the Dose Expansion (Part B) of this study.

• Participant is ≥ 18 years of age, at the time of signing the ICF.
• Participant must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Participant is willing and able to adhere to the study visit schedule and other protocol requirements.
• Relapsed or refractory acute myeloid leukemia (R/R AML) and relapsed or refractory higher-risk myelodysplastic syndromes (R/R HR-MDS) as defined by the World Health Organization (WHO) criteria who have failed or are ineligible for all available therapies which may provide clinical benefit
• Participant has Eastern Cooperative Oncology Group Performance Status of 0 to 2.

• Participants must have the following screening laboratory values:

  • Total White Blood Cell count (WBC) < 25 x 109/L prior to first infusion.
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤ 3.0 x upper limit of normal (ULN), unless considered due to leukemic organ involvement, in which case AST and ALT can be ≤ 5.0 x ULN.
  • Uric acid ≤ 7.5 mg/dL (446 μmol/L).
  • Serum total bilirubin ≤ 1.5 x ULN, unless considered due to Gilbert's syndrome
  • Estimated serum creatinine clearance of ≥ 60 mL/min using the Cockcroft-Gault equation. Measured creatinine clearance from a 24-hour urine collection is acceptable if clinically indicated.
  • INR < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN.

Exclusion Criteria:

The presence of any of the following will exclude a participant from enrollment:

• Participant has any condition, including active or uncontrolled infection, or the presence of laboratory abnormalities, which places the participant at unacceptable risk if the participant were to participate in the study.
• Any other significant medical condition, laboratory abnormality, or psychiatric illness which places the participant at unacceptable risk if he/she were to participate in the study or that would prevent the participant from complying with the study.
• Participant has any condition that confounds the ability to interpret data from the study.
• Participants with acute promyelocytic leukemia.
• Participants with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia.
• Participants with immediately life-threatening, severe complications of leukemia such as disseminated/uncontrolled infection, uncontrolled bleeding, and/or uncontrolled disseminated intravascular coagulation.
• Participants with impaired cardiac function or clinically significant cardiac diseases,
• Participants who have undergone major surgery ≤ 2 weeks prior to starting CC-91633. Participants must have recovered from any clinically significant effects of recent surgery.
• Pregnant or nursing individuals.
• Participants with known human immunodeficiency virus infection.
• Participants with known chronic, active hepatitis B virus or hepatitis C virus C (HCV) infection.
• Participants with ongoing treatment with chronic, therapeutic dosing of anticoagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors).
• Participants with history of concurrent second cancers requiring active, ongoing systemic treatment
• Participants with clinically significant diarrhea, vomiting or malabsorption felt to limit absorption of orally administered medications.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants with R/R AML and R/R HR-MDS - Part A; Part A (Dose Escalation) of the study will enroll R/R AML (Relapsed or Refractory Acute Myeloid Leukemia) and R/R HR-MDS (Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes) participants and will evaluate the safety and tolerability of escalating doses of CC-91633, administered orally, and determine the maximum tolerated dose (MTD) or preliminary recommended Phase 2 dose (RP2D) and schedule.	Drug: CC-91633; Administered orally according to the assigned treatment schedule; Other Names: BMS-986397
Experimental: Participants with Relapsed or Refractory Acute Myeloid Leukemia (R/R AML); Part B (expansion part) will confirm tolerability of the selected doses and schedules and evaluate whether efficacy is in a range that warrants further clinical development for R/R AML participants.	Drug: CC-91633; Administered orally according to the assigned treatment schedule; Other Names: BMS-986397
Experimental: Participants with Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes (HR-MDS); Part B (expansion part) will confirm tolerability of the selected doses and schedules and evaluate whether efficacy is in a range that warrants further clinical development for R/R HR-MDS participants.	Drug: CC-91633; Administered orally according to the assigned treatment schedule; Other Names: BMS-986397

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD)	Defined as the dose with highest posterior probability of the Dose-limiting toxicity (DLT) rate falling in the target interval and fulfilling escalation with overdose control (EWOC).	Up to 2 years
Dose-limiting Toxicity (DLT)	Defined as toxicities such as non-hematologic, confirmed Hy's law case, hematologic, or any AE toxicities meeting protocol specified DLT criteria and occurring within the DLT assessment period, unless the toxicity can clearly be determined to be due to other specified causes.	Up to 42 days after first dose of study treatment in Part A
Incidence of Adverse Events (AEs)	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 participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.	Up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Remission Rate (CRR)	Complete remission rate (CRR) is defined as the percent of participants whose best response is CRs including complete remission (CR), complete remission with partial hematologic recovery (CRh) and complete remission with incomplete hematologic recovery (CRi).	Up to 4 years
Efficacy determined by response rates of Acute Myeloid Leukemia (AML) - Minimal residual disease negative complete remission rate (CRRMRD-)	Minimal residual disease negative complete remission rate is defined as the percent of participants with Minimal residual disease negative complete remission.	Up to 4 years
Efficacy determined by response rates of Acute Myeloid Leukemia (AML) - Combined Complete Remission Rate (cCRR)	Combined complete remission rate (cCRR), is defined as the percent of participants whose best response is complete remission, includes minimal residual disease negative complete remission rate (CRRMRD-), morphologic complete remission, complete remission with incomplete hematologic recovery (CRi), complete remission with partial hematologic recovery (CRh).	Up to 4 years
Efficacy determined by response rates of Acute Myeloid Leukemia (AML) - Morphologic Leukemia-free State Rate (MLFSR)	The Morphologic Leukemia-free State Rate is defined as the percent of participants with the best response of Morphologic Leukemia-free State.	Up to 4 years
Partial Remission Rate (PRR)	Partial Remission Rate is defined as the percent of participant with the best response of Partial Remission.	Up to 4 years
Stable Disease Rate (SDR)	Stable Disease Rate is defined as the percent of participants with the best response of Stable Disease.	Up to 4 years
Progression-free Survival (PFS) rate at 3 and 9 months	Progression free survival rate is defined as the percent of participants with progression free for at least 3/9 months.	At 3 months and 9 months of PFS
Overall Survival (OS) rate	Overall survival rate is defined as the percent of participant who have survived for at least 6/12 months.	At 6 and 12 months of survival
Overall Response Rate (ORR)	Overall response rate is defined as the percent of participants whose best response is any of those composite complete response rate (cCRR) or morphologic Leukemia-free state (MLFS) or partial remission (PR) for AML and any of CR, marrow CR with HI (mCRHIR), PR, hematologic improvement (HI) for MDS.	Up to 4 years
Overall Survival (OS)	Overall Survival is measured as the time from the first dose of CC-91633 to death due to any cause.	Up to 4 years
Relapse-free Survival (RFS)	Relapse-free survival is defined only for participants who have achieved the best response of any of CR/CRh/CRi/CRRMRD- or any of PR/MLFS/mCRHIR/HI, and is measured as the interval from the date of first achieved of any CR/CRh/Cri/CRRMRD- or any of PR/ MLFS/mCRHIR/HI to the date of disease relapse or death from any cause, whichever occurs first.	Up to 4 years
Progression-free Survival (PFS)	Progression-Free Survival is defined as the time from the first dose of CC-91633 to the first occurrence of relapse or progression or death from any cause.	Up to 4 years
Event-free Survival (EFS)	Event-free Survival is defined as the interval from the date of the first dose to an event including disease progression, treatment failure, relapse, or death from any cause, whichever occurs first.	Up to 4 years
Duration of remission/response	For participants with best response of any of CR/CRh/ CRi/CRRMRD- or any of PR/MLFS/mCRHIR/HI, duration of remission/response is measured from the time when criteria for the best response of any of CR/CRh/ Cri/CRRMRD- or any of PR/ MLFS/mCRHIR/HI are first met (whichever is first recorded) until the first date at which relapse, or progressive disease is objectively documented assessment.	Up to 4 years
Time to remission/response	Time to onset of first remission/response is defined as the time interval from the date of first dose and the earliest date any remission/response (any CRs or PR) is observed.	Up to 4 years
Efficacy: Time to transformation to Acute Myeloid Leukemia (AML) for High-Risk Myelodysplastic Syndrome (HR-MDS)	Time interval from first dose to onset date of having 20% more bone marrow (BM) or peripheral blood (PB) blasts.	Up to 4 years
CC-91633 Pharmacokinetics - Cmax	Maximum plasma drug concentration.	Up to 4 years
CC-91633 Pharmacokinetics - AUC(0-T)	Area under the plasma concentration-time curve from time zero to time t, where t is the time point of the last measurable concentration.	Up to 4 years
CC-91633 Pharmacokinetics - AUC(TAU)	Area under the plasma concentration time-curve from time 0 to 24 hours postdose.	Up to 4 years
CC-91633 Pharmacokinetics - Tmax	Time to peak (maximum) plasma concentration.	Up to 4 years
CC-91633 Pharmacokinetics - T-HALF	Half-life.	Up to 4 years
CC-91633 Pharmacokinetics - CLT/F	Apparent total clearance of the drug from plasma after oral administration, as appropriate.	Up to 4 years
CC-91633 Pharmacokinetics - Vz/F	Apparent volume of distribution, as appropriate.	Up to 4 years
CC-2004772 Pharmacokinetics - Cmax	Maximum plasma drug concentration, if possible.	Up to 4 years
CC-2004772 Pharmacokinetics - AUC(0-T)	Area under the plasma concentration-time curve from time zero to time t, where t is the time point of the last measurable concentration, if possible.	Up to 4 years
CC-2004772 Pharmacokinetics - AUC(TAU)	Area under the plasma concentration time-curve from time 0 to 24 hours postdose, if possible.	Up to 4 years
CC-2004772 Pharmacokinetics - Tmax	Time to peak (maximum) plasma concentration, if possible.	Up to 4 years
CC-2004772 Pharmacokinetics - T-HALF	Half-life, if possible.	Up to 4 years
CC-2004772 Pharmacokinetics - CLT/F	Apparent total clearance of the drug from plasma after oral administration, if possible.	Up to 4 years
CC-2004772 Pharmacokinetics - Vz/F	Apparent volume of distribution, if possible.	Up to 4 years

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2021
• Primary Completion (Estimated): May 5, 2026
• Study Completion (Estimated): May 5, 2027

Study Registration Dates

• First Submitted: June 23, 2021
• First Submitted That Met QC Criteria: July 2, 2021
• First Posted (Actual): July 7, 2021

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Relapsed or Refractory Acute Myeloid Leukemia; Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia
• Other Study ID Numbers: CC-91633-AML-001; 2020-005329-95 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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