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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04951778
Recruitment Status : Recruiting
First Posted : July 7, 2021
Last Update Posted : June 7, 2022
Sponsor:
Information provided by (Responsible Party):
Celgene

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute Myelodysplastic Syndromes Drug: CC-91633 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 2, 2021
Estimated Primary Completion Date : November 5, 2025
Estimated Study Completion Date : October 26, 2027


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 Name: 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 Name: 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 Name: BMS-986397




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: Up to 2 years ]
    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).

  2. Dose-limiting Toxicity (DLT) [ Time Frame: Up to 42 days after first dose of study treatment in Part A ]
    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.

  3. Incidence of Adverse Events (AEs) [ Time Frame: Up to 4 years ]
    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.


Secondary Outcome Measures :
  1. Complete Remission Rate (CRR) [ Time Frame: Up to 4 years ]
    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).

  2. Efficacy determined by response rates of Acute Myeloid Leukemia (AML) - Minimal residual disease negative complete remission rate (CRRMRD-) [ Time Frame: Up to 4 years ]
    Minimal residual disease negative complete remission rate is defined as the percent of participants with Minimal residual disease negative complete remission.

  3. Efficacy determined by response rates of Acute Myeloid Leukemia (AML) - Combined Complete Remission Rate (cCRR) [ Time Frame: Up to 4 years ]
    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).

  4. Efficacy determined by response rates of Acute Myeloid Leukemia (AML) - Morphologic Leukemia-free State Rate (MLFSR) [ Time Frame: Up to 4 years ]
    The Morphologic Leukemia-free State Rate is defined as the percent of participants with the best response of Morphologic Leukemia-free State.

  5. Partial Remission Rate (PRR) [ Time Frame: Up to 4 years ]
    Partial Remission Rate is defined as the percent of participant with the best response of Partial Remission.

  6. Stable Disease Rate (SDR) [ Time Frame: Up to 4 years ]
    Stable Disease Rate is defined as the percent of participants with the best response of Stable Disease.

  7. Progression-free Survival (PFS) rate at 3 and 9 months [ Time Frame: At 3 months and 9 months of PFS ]
    Progression free survival rate is defined as the percent of participants with progression free for at least 3/9 months.

  8. Overall Survival (OS) rate [ Time Frame: At 6 and 12 months of survival ]
    Overall survival rate is defined as the percent of participant who have survived for at least 6/12 months.

  9. Overall Response Rate (ORR) [ Time Frame: Up to 4 years ]
    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.

  10. Overall Survival (OS) [ Time Frame: Up to 4 years ]
    Overall Survival is measured as the time from the first dose of CC-91633 to death due to any cause.

  11. Relapse-free Survival (RFS) [ Time Frame: Up to 4 years ]
    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.

  12. Progression-free Survival (PFS) [ Time Frame: Up to 4 years ]
    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.

  13. Event-free Survival (EFS) [ Time Frame: Up to 4 years ]
    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.

  14. Duration of remission/response [ Time Frame: Up to 4 years ]
    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.

  15. Time to remission/response [ Time Frame: Up to 4 years ]
    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.

  16. Efficacy: Time to transformation to Acute Myeloid Leukemia (AML) for High-Risk Myelodysplastic Syndrome (HR-MDS) [ Time Frame: Up to 4 years ]
    Time interval from first dose to onset date of having 20% more bone marrow (BM) or peripheral blood (PB) blasts.

  17. CC-91633 Pharmacokinetics - Cmax [ Time Frame: Up to 4 years ]
    Maximum plasma drug concentration.

  18. CC-91633 Pharmacokinetics - AUC(0-T) [ Time Frame: Up to 4 years ]
    Area under the plasma concentration-time curve from time zero to time t, where t is the time point of the last measurable concentration.

  19. CC-91633 Pharmacokinetics - AUC(TAU) [ Time Frame: Up to 4 years ]
    Area under the plasma concentration time-curve from time 0 to 24 hours postdose.

  20. CC-91633 Pharmacokinetics - Tmax [ Time Frame: Up to 4 years ]
    Time to peak (maximum) plasma concentration.

  21. CC-91633 Pharmacokinetics - T-HALF [ Time Frame: Up to 4 years ]
    Half-life.

  22. CC-91633 Pharmacokinetics - CLT/F [ Time Frame: Up to 4 years ]
    Apparent total clearance of the drug from plasma after oral administration, as appropriate.

  23. CC-91633 Pharmacokinetics - Vz/F [ Time Frame: Up to 4 years ]
    Apparent volume of distribution, as appropriate.

  24. CC-2004772 Pharmacokinetics - Cmax [ Time Frame: Up to 4 years ]
    Maximum plasma drug concentration, if possible.

  25. CC-2004772 Pharmacokinetics - AUC(0-T) [ Time Frame: Up to 4 years ]
    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.

  26. CC-2004772 Pharmacokinetics - AUC(TAU) [ Time Frame: Up to 4 years ]
    Area under the plasma concentration time-curve from time 0 to 24 hours postdose, if possible.

  27. CC-2004772 Pharmacokinetics - Tmax [ Time Frame: Up to 4 years ]
    Time to peak (maximum) plasma concentration, if possible.

  28. CC-2004772 Pharmacokinetics - T-HALF [ Time Frame: Up to 4 years ]
    Half-life, if possible.

  29. CC-2004772 Pharmacokinetics - CLT/F [ Time Frame: Up to 4 years ]
    Apparent total clearance of the drug from plasma after oral administration, if possible.

  30. CC-2004772 Pharmacokinetics - Vz/F [ Time Frame: Up to 4 years ]
    Apparent volume of distribution, if possible.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04951778


Contacts
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Contact: BMS Study Connect Contact Center www.BMSStudyConnect.com 855-907-3286 Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT # and Site #.

Locations
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United States, California
University of California San Diego Moores Cancer Center Not yet recruiting
La Jolla, California, United States, 92093
United States, Illinois
Northwestern University School of Medicine Not yet recruiting
Chicago, Illinois, United States, 60611-5975
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington Univ School of Medicine Siteman Cancer Center Recruiting
Saint Louis, Missouri, United States, 63110
United States, Ohio
The Ohio State University Comprehensive Cancer Center Not yet recruiting
Columbus, Ohio, United States, 43210
United States, Texas
The University of Texas - MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Spain
Vall d´Hebron University Hospital Recruiting
Barcelona, Spain, 08035
Hospital Clinic de Barcelona Recruiting
Barcelona, Spain, 08036
Hospital 12 de Octubre Recruiting
Madrid, Spain, 28041
Hospital Universitario Virgen Del Rocio Recruiting
Sevilla, Spain, 41013
Sponsors and Collaborators
Celgene
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT04951778    
Other Study ID Numbers: CC-91633-AML-001
2020-005329-95 ( EudraCT Number )
First Posted: July 7, 2021    Key Record Dates
Last Update Posted: June 7, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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/

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: See Plan Description
Access Criteria: See Plan Description
URL: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Celgene:
Relapsed or Refractory Acute Myeloid Leukemia
Relapsed or Refractory Higher-Risk Myelodysplastic Syndromes
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions