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

Leukemia, Myeloid Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04789655
• Other study ID #: CC-96191-AML-001
• Secondary ID: U1111-1264-54122
• Status: Recruiting
• Phase: Phase 1
• Start date: June 16, 2021
• Est. completion date: February 2, 2025

Study information

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

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: February 2, 2025
• Est. primary completion date: February 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Participants must satisfy the following criteria to be enrolled in the study:.

• Participant must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessments/procedures being conducted.

• Participant is = 18 years of age at the time of signing the ICF.

• 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.

• Participant has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.

• At least 4 weeks (from first dose) has elapsed from donor lymphocyte infusion without conditioning.

• 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.

• Participant with isolated extramedullary disease without bone marrow involvement.

• Inadequate pulmonary function as defined as oxygen saturation (SpO2) < 92% on room air.

• Other protocol-defined Inclusion/Exclusion criteria apply.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• CC-96191
CC-96191

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Center	Calgary	Alberta
Canada	Local Institution - 201	Toronto	Ontario
France	Institut Paoli Calmette Hematologie	Marseille cedex
France	Hopital Saint Louis	Paris
France	Hopital Haut Leveque	Pessac Cedex
France	Gustave Roussy	Villejuif CEDEX
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	The University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Mt. Sinai Medical Center Division of Hematology/Oncology	New York	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	Swedish Cancer Institute	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Canada,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Adverse Events (AEs)	Type, frequency, seriousness, severity and relationship of AEs to CC-96191	Up to 35 days after the last dose
Secondary	Complete remission rate (CRR)	As defined by the European Leukemia Net (ELN) AML response criteria.	Up to approximately 2 years
Secondary	Objective response rate (ORR)	As defined by the European Leukemia Net (ELN) AML response criteria.	Up to approximately 2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Pharmacokinetics - Cmax	Maximum serum concentration of drug	Up to 35 days after last dose
Secondary	Pharmacokinetics - AUC	Area under the serum concentration time-curve	Up to 35 days after last dose
Secondary	Pharmacokinetics - tmax	Time to peak (maximum) serum concentration	Up to 35 days after last dose
Secondary	Pharmacokinetics - t1/2	Terminal half-life	Up to 35 days after last dose
Secondary	Pharmacokinetics - CL	Total body clearance of the drug from the serum	Up to 35 days after last dose
Secondary	Pharmacokinetics - Vss	Volume of distribution at steady-state	Up to 35 days after last dose
Secondary	Presence of anti-drug antibodies (ADA)	Detection of anti-drug antibodies in participants	Up to 35 days after last dose
Secondary	Frequency of anti-drug antibodies (ADA)	Frequency of anti-drug antibodies in participants	Up to 35 days after last dose

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting