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

Sponsor

Celgene (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04789655

Collaborator

(none)

Enrollment

Locations

Arm

43.6

Anticipated Duration (Months)

4.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Myeloid	Drug: CC-96191	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 16, 2021

Anticipated Primary Completion Date :

Feb 1, 2025

Anticipated Study Completion Date :

Feb 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CC-96191 CC-96191 will be administered intravenously on a 28-day Cycle	Drug: CC-96191 CC-96191

Arm

Intervention/Treatment

Experimental: CC-96191

CC-96191 will be administered intravenously on a 28-day Cycle

Drug: CC-96191

CC-96191

Outcome Measures

Primary Outcome Measures

Dose limiting toxicities (DLTs) [Up to 42 days after the first dose]
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.
Maximum tolerated dose (MTD) [Up to 35 days after the last dose]
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.
Adverse Events (AEs) [Up to 35 days after the last dose]
Type, frequency, seriousness, severity and relationship of AEs to CC-96191

Secondary Outcome Measures

Complete remission rate (CRR) [Up to approximately 2 years]
As defined by the European Leukemia Net (ELN) AML response criteria.
Objective response rate (ORR) [Up to approximately 2 years]
As defined by the European Leukemia Net (ELN) AML response criteria.
Progression-free survival (PFS) [Up to approximately 2 years]
Is defined as the time from the first dose of CC-96191 to the first occurrence of disease progression or death from any cause.
Overall survival (OS) [Up to approximately 2 years]
Is measured as the time from the first dose of CC-96191 to death due to any cause.
Pharmacokinetics - Cmax [Up to 35 days after last dose]
Maximum serum concentration of drug
Pharmacokinetics - AUC [Up to 35 days after last dose]
Area under the serum concentration time-curve
Pharmacokinetics - tmax [Up to 35 days after last dose]
Time to peak (maximum) serum concentration
Pharmacokinetics - t1/2 [Up to 35 days after last dose]
Terminal half-life
Pharmacokinetics - CL [Up to 35 days after last dose]
Total body clearance of the drug from the serum
Pharmacokinetics - Vss [Up to 35 days after last dose]
Volume of distribution at steady-state
Presence of anti-drug antibodies (ADA) [Up to 35 days after last dose]
Detection of anti-drug antibodies in participants
Frequency of anti-drug antibodies (ADA) [Up to 35 days after last dose]
Frequency of anti-drug antibodies in participants

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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. 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.
Participant has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2.
At least 4 weeks (from first dose) has elapsed from donor lymphocyte infusion without conditioning.
Participants must have adequate hematologic, liver, renal, and coagulation function as assessed by laboratory tests 9. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
3	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
4	Mayo Clinic	Rochester	Minnesota	United States	55905
5	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
6	Mt. Sinai Medical Center Division of Hematology/Oncology	New York	New York	United States	10029
7	The University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030
8	Swedish Cancer Institute	Seattle	Washington	United States	98109
9	Tom Baker Cancer Center	Calgary	Alberta	Canada	T2N 4N2
10	Princess Margaret Hospital University Health Network	Toronto	Ontario	Canada	M5G 2M9
11	Institut Paoli Calmette Hematologie	Marseille cedex		France	13273
12	Hopital Saint Louis	Paris		France	75010
13	Hopital Haut Leveque	Pessac Cedex		France	33604
14	Gustave Roussy	Villejuif CEDEX		France	94805
15	Local Institution - 302	Villejuif CEDEX		France	94805