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

Myelodysplastic Syndromes Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04951778
• Other study ID #: CC-91633-AML-001
• Secondary ID: 2020-005329-95
• Status: Recruiting
• Phase: Phase 1
• Start date: December 2, 2021
• Est. completion date: May 5, 2027

Study information

• Verified date: March 2024
• Source: Celgene
• Contact: BMS Study Connect Contact Center www.BMSStudyConnect.com
• Phone: 855-907-3286
• Email: Clinical.Trials[@]bms.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: May 5, 2027
• Est. primary completion date: May 5, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• CC-91633
Administered orally according to the assigned treatment schedule

Locations

Country	Name	City	State
Australia	Local Institution - 604	Adelaide	South Australia
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Monash Health	Clayton	Victoria
Australia	Local Institution - 603	Melbourne	Victoria
Australia	St Vincent's Hospital	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Canada	Local Institution - 201	Ottawa	Ontario
Canada	Local Institution - 202	Toronto	Ontario
Canada	Local Institution - 203	Vancouver	British Columbia
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Vall d Hebron University Hospital	Barcelona
Spain	Local Institution - 303	Madrid
Spain	Hospital Universitario Virgen del Rocio	Sevilla
United Kingdom	Local Institution - 503	Leeds
United Kingdom	Local Institution - 502	London	London, City Of
United Kingdom	Local Institution - 505	London
United Kingdom	Local Institution - 504	Manchester	Greater Manchester
United Kingdom	Local Institution - 501	Oxford
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Local Institution - 110	Chicago	Illinois
United States	Northwestern University School Of Medicine	Chicago	Illinois
United States	Local Institution - 102	Columbus	Ohio
United States	Local Institution - 111	Gilbert	Arizona
United States	The University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Local Institution - 103	La Jolla	California
United States	Local Institution - 108	Philadelphia	Pennsylvania
United States	Washington Univ School of Medicine Siteman Cancer Center	Saint Louis	Missouri
United States	Local Institution - 109	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	CC-91633 Pharmacokinetics - Cmax	Maximum plasma drug concentration.	Up to 4 years
Secondary	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
Secondary	CC-91633 Pharmacokinetics - AUC(TAU)	Area under the plasma concentration time-curve from time 0 to 24 hours postdose.	Up to 4 years
Secondary	CC-91633 Pharmacokinetics - Tmax	Time to peak (maximum) plasma concentration.	Up to 4 years
Secondary	CC-91633 Pharmacokinetics - T-HALF	Half-life.	Up to 4 years
Secondary	CC-91633 Pharmacokinetics - CLT/F	Apparent total clearance of the drug from plasma after oral administration, as appropriate.	Up to 4 years
Secondary	CC-91633 Pharmacokinetics - Vz/F	Apparent volume of distribution, as appropriate.	Up to 4 years
Secondary	CC-2004772 Pharmacokinetics - Cmax	Maximum plasma drug concentration, if possible.	Up to 4 years
Secondary	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
Secondary	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
Secondary	CC-2004772 Pharmacokinetics - Tmax	Time to peak (maximum) plasma concentration, if possible.	Up to 4 years
Secondary	CC-2004772 Pharmacokinetics - T-HALF	Half-life, if possible.	Up to 4 years
Secondary	CC-2004772 Pharmacokinetics - CLT/F	Apparent total clearance of the drug from plasma after oral administration, if possible.	Up to 4 years
Secondary	CC-2004772 Pharmacokinetics - Vz/F	Apparent volume of distribution, if possible.	Up to 4 years

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