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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Leukemia, Myeloid
• Intervention / Treatment: Drug: CC-96191

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: BMS Study Connect Contact Center http://www.bmsstudyconnect.com; Phone Number: 855-907-3286; Email: Clinical.Trials@bms.com
• Study Contact Backup: Name: First line of the email MUST contain the NCT# and Site #

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Recruiting
      • Local Institution - 202
      • Contact: Site 202
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Local Institution - 201
      • Contact: Site 201
• France
  • Marseille cedex, France, 13273
    • Recruiting
    • Institut Paoli Calmette Hematologie
    • Contact: Sylvain Garciaz, Site 303; Phone Number: 0491223333
  • Paris, France, 75010
    • Recruiting
    • Hopital Saint Louis
    • Contact: Emmanuel Raffoux, Site 304; Phone Number: 33142499649
  • Pessac Cedex, France, 33604
    • Recruiting
    • Hopital Haut Leveque
    • Contact: Pierre Yves Dumas, Site 301
  • Villejuif CEDEX, France, 94805
    • Recruiting
    • Gustave Roussy
    • Contact: Stephane De Botton, Site 302; Phone Number: +33 1 42 11 40 79
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama at Birmingham
      • Contact: Pankit Vachhani, Site 109
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic - Jacksonville
      • Contact: James Foran, Site 105; Phone Number: 205-934-2248
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Winship Cancer Institute of Emory University
      • Contact: William Blum, Site 108; Phone Number: 614-406-4123
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: Mithun Shah, Site 110
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Hackensack University Medical Center
      • Contact: Jaime Koprivnikar, Site 101
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Mt. Sinai Medical Center Division of Hematology/Oncology
      • Contact: John Mascarenhas, Site 102; Phone Number: 212-241-4106
  • Texas
    • Houston, Texas, United States, 77030-4009
      • Recruiting
      • The University of Texas - MD Anderson Cancer Center
      • Contact: Tapan Kadia, Site 107; Phone Number: 713-563-3534
  • Washington
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Swedish Cancer Institute
      • Contact: Daniel Egan, Site 111; Phone Number: 617-699-2437

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

1. Participant is suspected or proven to have acute promyelocytic leukemia (FAB M3) based on morphology, immunophenotype, molecular assay, or karyotype.
2. 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.
3. 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).
4. Prior allogeneic HSCT with either standard or reduced intensity conditioning ≤ 6 months prior to dosing.
5. 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.
6. Participant has persistent, clinically significant non-hematologic toxicities from prior therapies which have not recovered to < Grade 2.
7. 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.
8. History of concurrent second cancers requiring active, ongoing systemic treatment.
9. Participant is known seropositive or active infection with human immunodeficiency virus (HIV), or active infection with hepatitis B virus or hepatitis C virus.
10. Impaired cardiac function or clinically significant cardiac diseases, as defined in the protocol .
11. Participant is a pregnant or lactating female.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2021
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): February 2, 2025

Study Registration Dates

• First Submitted: February 26, 2021
• First Submitted That Met QC Criteria: March 8, 2021
• First Posted (Actual): March 9, 2021

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; CC-96191; Relapsed or refractory
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: CC-96191-AML-001; U1111-1264-5412 (Registry Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No