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A Safety and Efficacy Study of CC-90009 Combinations in Subjects With Acute Myeloid Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04336982
Recruitment Status : Recruiting
First Posted : April 7, 2020
Last Update Posted : March 10, 2023
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Celgene

Study Description
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Brief Summary:
CC-90009-AML-002 is an exploratory Phase 1b, open-label, multi-arm trial to evaluate the safety and efficacy of CC-90009 in combination with anti-leukemia agents in participants with acute myeloid leukemia (AML).

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute Drug: CC-90009 Drug: Venetoclax Drug: Azacitidine Drug: Gilteritinib Phase 1 Phase 2

Detailed Description:

Study CC-90009-AML-002 is an open-label, multi-arm, parallel multi-cohort, multicenter, Phase 1b study to determine the safety, tolerability, PK, and efficacy of CC 90009 in combination with anti-leukemia agents used for the treatment of AML. CC 90009 will be given as a combination therapy to subjects with newly diagnosed (ND) or relapsed or refractory (R/R) AML.

The dose and schedule finding part (Part A) of the study will evaluate the safety, PK and PD data, and preliminary efficacy information and determine the Part B dose and schedule for each arm.

The expansion part (Part B) of the study will further evaluate the safety and efficacy of the CC-90009 containing combination at or below the maximum tolerated dose (MTD) in the selected cohorts in order to determine the recommended Phase 2 dose (RP2D) for subjects with AML.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 43 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Exploratory Phase 1b Open-label Multi-arm Trial to Evaluate the Safety and Efficacy of CC-90009 in Combination With Anti-Leukemia Agents in Subjects With Acute Myeloid Leukemia
Actual Study Start Date : August 5, 2020
Estimated Primary Completion Date : January 26, 2024
Estimated Study Completion Date : January 25, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: CC-90009 in combination with venetoclax and azacitidine

CC-90009 will be administered intravenously per dosing schedule in a 28-day cycle. Venetoclax will be administered orally QD.

Azacitidine will be administered intravenously or subcutaneously on planned dosing days for each cycle.

 Drug: CC-90009
Injection

Drug: Venetoclax
Tablet

Drug: Azacitidine
Injection
Experimental: CC-90009 in combination with gilteritinib
CC-90009 will be administered intravenously per dosing schedule in a 28-day cycle. Gilteritinib will be administered orally QD.
 Drug: Gilteritinib
Tablet


Outcome Measures
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Primary Outcome Measures :
  1. Dose Limiting Toxicity (DLT) [ Time Frame: Up to 28 days ]
    Number of participants with a DLT

  2. Adverse Events (AEs) [ Time Frame: Up to 28 days after last dose of study drug. ]
    An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology.


Secondary Outcome Measures :
  1. Complete Remission Rate (CRR), [ Time Frame: Up to 3 years ]
    is defined as the rate for any type of CR or CRh

  2. Objective Response Rate (ORR) [ Time Frame: Up to 3 years ]
    includes all responses of complete remissions (CRs), Morphologic leukemia-free state (MLFS), and Partial remission (PR)

  3. Progression Free Survival (PFS) [ Time Frame: Up to 3 years ]
    is defined as the time from the first dose of study drug(s) to the first occurrence of relapse or progression or death from any cause

  4. Overall Survival (OS) [ Time Frame: Up to 3 years ]
    is measured as the time from the first dose of study drug(s) to death due to any cause and will be analyzed in a manner similar to that described for PFS.

  5. Duration of Remission [ Time Frame: Up to 3 years ]
    is measured from the time when criteria for CR/CRh/PR are first met (whichever is first recorded) until the first date at which relapse, or progressive disease is objectively documented.

  6. Time to Remission [ Time Frame: Up to 3 years ]
    is measured from the time when criteria for CR/CRh/PR are first met (whichever is first recorded)

  7. Pharmacokinetics - Cmax [ Time Frame: Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3) ]
    observed maximum concentration in plasma

  8. Pharmacokinetics - AUC24 [ Time Frame: Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3) ]
    area under the plasma concentration time-curve from time 0 to 24 hours postdose

  9. Pharmacokinetics - t1/2 [ Time Frame: Until last CC-90009 dose in Cycle 3 (each cycle is 28 days. CC-90009 dosing days are Days 1-5 in Cycle 3) ]
    terminal half life


Eligibility Criteria
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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.

  2. Arm A (CC-90009 + venetoclax/azacitidine):

    1. Part A: Newly diagnosed AML with poor/adverse risk genetic abnormalities and is ≥ 75 years of age or intensive chemotherapy ineligible OR
    2. Part A: Refractory AML and is ≥ 18 years of age
    3. Part B: Newly diagnosed AML and is ≥ 75 years of age or intensive chemotherapy ineligible

  3. Arm B (CC-90009 + gilteritinib):

    1. Subject is ≥ 18 years of age.
    2. Fms-like tyrosine kinase 3 (FLT3) mutation positive.
    3. Gilteritinib treatment naïve
  4. Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

  5. Subject must have the following screening laboratory values:

    • Total White Blood Cell count (WBC) < 25 x 10^9/L prior to study treatments. Treatment with hydroxyurea to achieve this level is allowed.

    • Selected electrolytes within normal limits or correctable with supplements.

      • Participant must have adequate liver function as demonstrated by: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) and bilirubin ≤ 1.5 x ULN
      • Participant has adequate renal function as demonstrated by an estimated serum creatinine clearance of ≥ 60 mL/min using the Cockcroft-Gault equation.
  6. Agree to follow the CC-90009 Pregnancy Prevention Plan (PPP) and combination agents' requirements.

Exclusion Criteria:

  1. Subject with acute promyelocytic leukemia (APL)
  2. Subject 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
  3. Patients with prior autologous hematopoietic stem cell transplant (HSCT) 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. Subject 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. Subject has persistent, clinically significant non-hematologic toxicities from prior therapies which have not recovered to < Grade 2
  7. Subject 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. Disorders or conditions disrupting normal calcium homeostasis or preventing calcium supplementation.

  9. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:

    1. Left ventricular ejection fraction (LVEF) < 45% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO).
    2. Complete left bundle branch or bifascicular block.
    3. Congenital long QT syndrome.
    4. Persistent or clinically meaningful ventricular arrhythmias.
    5. QTcF ≥ 470 ms (Arm A) or > 450 ms (Arm B) on Screening electrocardiogram (ECG)
    6. Unstable angina pectoris or myocardial infarction ≤ 6 months prior to starting study treatments or unstable arrhythmia.
    7. Cardiovascular disability status of New York Heart Association Class ≥2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
  10. Subject is a pregnant or lactating female

  11. Additional exclusion criteria based on combination agent:

    a. For Combination Arm A (venetoclax/azacitidine):

    • Received strong or moderate CYP3A inhibitors or inducers or P-gp inhibitors within 7 days prior to initiation of first venetoclax dose.
    • Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or Star fruit within 3 days prior to first venetoclax dose through last dose of venetoclax.

  12. Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to C1D1.

    a. Acute symptoms must have resolved and based on investigator assessment in consultation with the medical monitor, there are no sequelae that would place the participant at a higher risk of receiving study treatment.

  13. Previous SARS-CoV-2 vaccine within 14 days of C1D1.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04336982


Contacts
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Contact: BMS Study Connect Contact Center www.BMSStudyConnect.com 855-907-3286 Clinical.Trials@bms.com
Contact: First line of the email MUST contain the NCT# and Site #

Locations
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United States, California
University Of California, San Francisco Recruiting
San Francisco, California, United States, 94143-0324
Contact: Catherine Smith, Site 104         
United States, Connecticut
Yale New Haven Hospital Recruiting
New Haven, Connecticut, United States, 06510
Contact: Amer Zeidan, Site 107    203-737-7078      
United States, Massachusetts
Dana-Farber/Mass General Brigham Cancer Care, Inc Recruiting
Boston, Massachusetts, United States, 02115
Contact: Daniel DeAngelo, Site 103    617-632-3712      
United States, Missouri
Washington University School Of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Geoffrey Uy, Site 101    314-454-8304      
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Jaime Koprivnikar, Site 108         
United States, Texas
The University of Texas - MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Courtney DiNardo, Site 105    713-794-1141      
United States, Washington
Fred Hutchinson Cancer Center Recruiting
Seattle, Washington, United States, 98109-1024
Contact: Mary-Elizabeth Percival, Site 102         
Canada, Alberta
Local Institution - 202 Recruiting
Edmonton, Alberta, Canada, T6G 2R7
Contact: Site 202         
Canada, Ontario
Local Institution - 201 Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Site 201         
Canada, Quebec
Local Institution - 203 Withdrawn
Montreal, Quebec, Canada, H1T 2M4
France
Local Institution - 402 Recruiting
Marseille, France, 13273
Contact: Site 402         
Local Institution - 401 Recruiting
Pessac Cedex, France, 33604
Contact: Site 401         
Local Institution - 404 Recruiting
Toulouse Cedex 9, France, 31059
Contact: Site 404         
United Kingdom
Local Institution - 301 Recruiting
Oxford, United Kingdom, OX3 9DU
Contact: Site 301         
Sponsors and Collaborators
Celgene
AbbVie
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT04336982    
Other Study ID Numbers: CC-90009-AML-002
U1111-1247-5619 ( Other Identifier: WHO )
2019-001681-15 ( EudraCT Number )
First Posted: April 7, 2020    Key Record Dates
Last Update Posted: March 10, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: See Plan Description
Access Criteria: See Plan Description
URL: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Celgene:
CC-90009
Venetoclax
Azacitidine
Gilteritinib
 Hematologic cancers
Leukemia
Acute myeloid leukemia
AML
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Azacitidine
 Venetoclax
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors