Study of CC-96191 in Participants With Relapsed or Refractory Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This Phase 1, clinical study of CC-96191 will explore the safety, tolerability and preliminary biological and clinical activity of CC-96191 as a single-agent in the setting of Relapsed or refractory acute myeloid leukemia (R/R AML). The dose escalation (Part A) of the study will explore escalating intravenous doses of CC-96191 to estimate the MTD and/or RP2D of CC-96191 as monotherapy. The expansion (Part B), will further evaluate the safety and efficacy of CC-96191 administered at or below the MTD in one or more expansion cohorts in order to determine the RP2D.

Official Title
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A Phase 1, Multi-center, Open-label, Dose Finding Study of CC-96191 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia

Conditions
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Leukemia, Myeloid

Intervention / Treatment
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* Drug: CC-96191


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must satisfy the following criteria to be enrolled in the study: 1. Participant must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted. 3. Participant is ≥ 18 years of age at the time of signing the ICF. 4. Relapsed or refractory CD33 positive AML at last visit as defined by the World Health Organization (WHO) Classification who have failed or who are ineligible for or have refused all available therapies for AML which may provide clinical benefit. 6. Participant has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. 7. At least 4 weeks (from first dose) has elapsed from donor lymphocyte infusion without conditioning. 8. Females and males must practice true abstinence or agree to contraceptive methods throughout the study, and during the safety follow-up period. Exclusion Criteria: The presence of any of the following will exclude a Participant from enrollment: Participant is suspected or proven to have acute promyelocytic leukemia (FAB M3) based on morphology, immunophenotype, molecular assay, or karyotype. Participant has received systemic anticancer therapy (including investigational therapy) or radiotherapy < 28 days or 5 half-lives, whichever is shorter, prior to the start of study treatment. Hydroxyurea is allowed to control peripheral leukemia blasts. Participants with prior autologous hematopoietic stem cell transplant who, in the investigator's judgment, have not fully recovered from the effects of the last transplant (eg, transplant-related side effects). Prior allogeneic HSCT with either standard or reduced intensity conditioning ≤ 6 months prior to dosing. Participants on systemic immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD). The use of topical steroids for ongoing skin or ocular GVHD is permitted. Participant has persistent, clinically significant non-hematologic toxicities from prior therapies which have not recovered to < Grade 2. Participant has or is suspected of having central nervous system (CNS) leukemia. Evaluation of cerebrospinal fluid is only required if CNS involvement by leukemia is suspected during screening. History of concurrent second cancers requiring active, ongoing systemic treatment. Participant is known seropositive or active infection with human immunodeficiency virus (HIV), or active infection with hepatitis B virus or hepatitis C virus. Impaired cardiac function or clinically significant cardiac diseases, as defined in the protocol . Participant is a pregnant or lactating female.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CC-96191<br>CC-96191 will be administered intravenously on a 28-day Cycle | Drug: CC-96191<br>* CC-96191<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicities (DLTs) | Are defined as toxicities that meet the protocol-specified criteria occurring within the DLT assessment window (Cycle 1, Days 1 to at least 28 and up to 42 days) that cannot be attributed to a clearly identifiable cause such as underlying illness, disease progression, other concurrent illness, or concomitant medication. | Up to 42 days after the first dose | 
| Maximum tolerated dose (MTD) | Is defined as the highest dose at which less than 33% of the population treated with CC-96191 experience a dose limiting toxicity (DLT) in the first cycle. | Up to 35 days after the last dose | 
| Adverse Events (AEs) | Type, frequency, seriousness, severity and relationship of AEs to CC-96191 | Up to 35 days after the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission rate (CRR) | As defined by the European Leukemia Net (ELN) AML response criteria. | Up to approximately 2 years | 
| Objective response rate (ORR) | As defined by the European Leukemia Net (ELN) AML response criteria. | Up to approximately 2 years | 
| Progression-free survival (PFS) | Is defined as the time from the first dose of CC-96191 to the first occurrence of disease progression or death from any cause. | Up to approximately 2 years | 
| Overall survival (OS) | Is measured as the time from the first dose of CC-96191 to death due to any cause. | Up to approximately 2 years | 
| Duration of remission | For subjects with best response of complete remission (CR) of any type, morphologic leukemia free state (MLFS) or partial remission (PR), duration of response (DOR) is measured from the time when criteria for CR/MLFS/PR are first met (whichever is first recorded) until the first date at which relapse, or progressive disease is objectively documented | Up to approximately 2 years | 
| Time to remission | Time from the date of first dose to the earliest date of any response (CR of any type, MLFS or PR) | Up to approximately 2 years | 
| Pharmacokinetics - Cmax | Maximum serum concentration of drug | Up to 35 days after last dose | 
| Pharmacokinetics - AUC | Area under the serum concentration time-curve | Up to 35 days after last dose | 
| Pharmacokinetics - tmax | Time to peak (maximum) serum concentration | Up to 35 days after last dose | 
| Pharmacokinetics - t1/2 | Terminal half-life | Up to 35 days after last dose | 
| Pharmacokinetics - CL | Total body clearance of the drug from the serum | Up to 35 days after last dose | 
| Pharmacokinetics - Vss | Volume of distribution at steady-state | Up to 35 days after last dose | 
| Presence of anti-drug antibodies (ADA) | Detection of anti-drug antibodies in participants | Up to 35 days after last dose | 
| Frequency of anti-drug antibodies (ADA) | Frequency of anti-drug antibodies in participants | Up to 35 days after last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Myeloid Leukemia, CC-96191, Relapsed or refractory