Clinical trial NCT04789655: Study of CC-96191 in Participants With Relapsed or Refractory Acute Myeloid Leukemia
Official title: A Phase 1, Multi-center, Open-label, Dose Finding Study of CC-96191 in Subjects With Relapsed or Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Leukemia, Myeloid
Keywords: Acute Myeloid Leukemia
CC-96191
Relapsed or refractory
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2021-03-09
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Dose limiting toxicities (DLTs)
timeFrame: Up to 42 days after the first dose
measure: Maximum tolerated dose (MTD)
timeFrame: Up to 35 days after the last dose
measure: Adverse Events (AEs)
timeFrame: Up to 35 days after the last dose
Secondary outcomes:
measure: Complete remission rate (CRR)
timeFrame: Up to approximately 2 years
measure: Objective response rate (ORR)
timeFrame: Up to approximately 2 years
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 2 years
measure: Overall survival (OS)
timeFrame: Up to approximately 2 years
measure: Duration of remission
timeFrame: Up to approximately 2 years
measure: Time to remission
timeFrame: Up to approximately 2 years
measure: Pharmacokinetics - Cmax
timeFrame: Up to 35 days after last dose
measure: Pharmacokinetics - AUC
timeFrame: Up to 35 days after last dose
measure: Pharmacokinetics - tmax
timeFrame: Up to 35 days after last dose
measure: Pharmacokinetics - t1/2
timeFrame: Up to 35 days after last dose
measure: Pharmacokinetics - CL
timeFrame: Up to 35 days after last dose
measure: Pharmacokinetics - Vss
timeFrame: Up to 35 days after last dose
measure: Presence of anti-drug antibodies (ADA)
timeFrame: Up to 35 days after last dose
measure: Frequency of anti-drug antibodies (ADA)
timeFrame: Up to 35 days after last dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Local Institution - 109
state: Alabama
city: Jacksonville
country: United States
facility: Local Institution - 105
state: Florida
city: Atlanta
country: United States
facility: Local Institution - 108
state: Georgia
city: Rochester
country: United States
facility: Local Institution - 110
state: Minnesota
city: Hackensack
country: United States
facility: Local Institution - 101
state: New Jersey
city: New York
country: United States
facility: Local Institution - 102
state: New York
city: Houston
country: United States
facility: Local Institution - 107
state: Texas
city: Seattle
country: United States
facility: Local Institution - 111
state: Washington
city: Calgary
country: Canada
facility: Local Institution - 202
state: Alberta
city: Toronto
country: Canada
facility: Local Institution - 201
state: Ontario
city: Marseille cedex
country: France
facility: Local Institution - 303
city: Paris
country: France
facility: Local Institution - 304
city: Pessac Cedex
country: France
facility: Local Institution - 301
city: Villejuif CEDEX
country: France
facility: Local Institution - 302
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: