NCT04951778 - 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 | Crick

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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. * Participants with known or suspected hypersensitivity to any of the components or excipients of the study treatment or to similar class drugs (eg, lenalidomide).

Outcomes

Primary Outcomes

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).

Time frame: 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.

Time frame: 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.

Time frame: Up to 4 years

Secondary Outcomes

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).

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Up to 4 years

CC-91633 Pharmacokinetics - Cmax

Maximum plasma drug concentration.

Time frame: 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.

Time frame: Up to 4 years

CC-91633 Pharmacokinetics - AUC(TAU)

Area under the plasma concentration time-curve from time 0 to 24 hours postdose.

Time frame: Up to 4 years

CC-91633 Pharmacokinetics - Tmax

Time to peak (maximum) plasma concentration.

Time frame: Up to 4 years

CC-91633 Pharmacokinetics - T-HALF

Half-life.

Time frame: Up to 4 years

CC-91633 Pharmacokinetics - CLT/F

Apparent total clearance of the drug from plasma after oral administration, as appropriate.

Time frame: Up to 4 years

CC-91633 Pharmacokinetics - Vz/F

Apparent volume of distribution, as appropriate.

Time frame: Up to 4 years

CC-2004772 Pharmacokinetics - Cmax

Maximum plasma drug concentration, if possible.

Time frame: 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.

Time frame: 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.

Time frame: Up to 4 years

CC-2004772 Pharmacokinetics - Tmax

Time to peak (maximum) plasma concentration, if possible.

Time frame: Up to 4 years

CC-2004772 Pharmacokinetics - T-HALF

Half-life, if possible.

Time frame: Up to 4 years

CC-2004772 Pharmacokinetics - CLT/F

Apparent total clearance of the drug from plasma after oral administration, if possible.

Time frame: Up to 4 years

CC-2004772 Pharmacokinetics - Vz/F

Apparent volume of distribution, if possible.

Time frame: Up to 4 years

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

Overview

Conditions

Interventions

Eligibility

Locations (9)

Outcomes

Primary Outcomes

Secondary Outcomes