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

NCT04336982 | Terminated Phase 1 FDA Drug

• 3 other identifiers: CC-90009-AML-002U1111-1247-56192019-001681-15
• Study Type: interventional
• Target: 22
• Locations: 5 countries
• Sites: 14

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).

Conditions

Leukemia, Myeloid, Acute

Keywords

CC-90009; Venetoclax; Azacitidine; Gilteritinib; Hematologic cancers; Leukemia; Acute myeloid leukemia; AML

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity (DLT)

  Number of participants with a DLT

  Up to 28 days

• Adverse Events (AEs)

  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.

  Up to 28 days after last dose of study drug.

Secondary Outcomes (9)

• Complete Remission Rate (CRR),

  Up to 3 years

• Objective Response Rate (ORR)

  Up to 3 years

• Progression Free Survival (PFS)

  Up to 3 years

• Overall Survival (OS)

  Up to 3 years

• Duration of Remission

  Up to 3 years

Study Arms (2)

CC-90009 in combination with venetoclax and azacitidine

EXPERIMENTAL

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; Drug: Venetoclax; Drug: Azacitidine

CC-90009 in combination with gilteritinib

EXPERIMENTAL

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

Drug: Gilteritinib

Interventions

CC-90009 DRUG

Injection

CC-90009 in combination with venetoclax and azacitidine

Venetoclax DRUG

Tablet

CC-90009 in combination with venetoclax and azacitidine

Azacitidine DRUG

Injection

CC-90009 in combination with venetoclax and azacitidine

Gilteritinib DRUG

Tablet

CC-90009 in combination with gilteritinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Arm A (CC-90009 + venetoclax/azacitidine):
• Part A: Newly diagnosed AML with poor/adverse risk genetic abnormalities and is either ≥ 75 years of age or is ineligible for intensive chemotherapy OR
• Part A: Primary Refractory AML, or AML in first relapse, and is ≥ 18 years of age
• Part B: Newly diagnosed AML and is ≥ 75 years of age or intensive chemotherapy ineligible
• Arm B (CC-90009 + gilteritinib):
• Subject is ≥ 18 years of age.
• Fms-like tyrosine kinase 3 (FLT3) mutation positive.
• Gilteritinib treatment naïve
• Subject has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• 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 ≥ 30 mL/min.

You may not qualify if:

• Subject with acute promyelocytic leukemia (APL)
• 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
• 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)
• Prior allogeneic HSCT with either standard or reduced intensity conditioning ≤ 6 months prior to dosing
• 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
• Subject has persistent, clinically significant non-hematologic toxicities from prior therapies which have not recovered to \< Grade 2
• 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.
• Disorders or conditions disrupting normal calcium homeostasis or preventing calcium supplementation.
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• Left ventricular ejection fraction (LVEF) \< 45% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO).
• Complete left bundle branch or bifascicular block.
• Congenital long QT syndrome.
• Persistent or clinically meaningful ventricular arrhythmias.
• QTcF ≥ 470 ms (Arm A) or \> 450 ms (Arm B) on Screening electrocardiogram (ECG)
• Unstable angina pectoris or myocardial infarction ≤ 6 months prior to starting study treatments or unstable arrhythmia.

Sponsors & Collaborators

• Celgene: lead
• AbbVie: collaborator

Study Sites (14)

Local Institution - 104

San Francisco, California, 94143-0324, United States

Location

Local Institution - 107

New Haven, Connecticut, 06510, United States

Location

Local Institution - 103

Boston, Massachusetts, 02115, United States

Location

Local Institution - 101

St Louis, Missouri, 63110, United States

Location

Local Institution - 108

Hackensack, New Jersey, 07601, United States

Location

Local Institution - 105

Houston, Texas, 77030-4009, United States

Location

Local Institution - 102

Seattle, Washington, 98109-1024, United States

Location

Local Institution - UNK3

Yvoir, 5530, Belgium

Location

Local Institution - 202

Edmonton, Alberta, T6G 2R7, Canada

Location

Local Institution - 201

Toronto, Ontario, M5G 2M9, Canada

Location

Local Institution - 402

Marseille, 13273, France

Location

Local Institution - 401

Pessac, 33604, France

Location

Local Institution - 404

Toulouse, 31059, France

Location

Local Institution - 301

Oxford, OX3 9DU, United Kingdom

Location

Related Publications (1)

• Surka C, Jin L, Mbong N, Lu CC, Jang IS, Rychak E, Mendy D, Clayton T, Tindall E, Hsu C, Fontanillo C, Tran E, Contreras A, Ng SWK, Matyskiela M, Wang K, Chamberlain P, Cathers B, Carmichael J, Hansen J, Wang JCY, Minden MD, Fan J, Pierce DW, Pourdehnad M, Rolfe M, Lopez-Girona A, Dick JE, Lu G. CC-90009, a novel cereblon E3 ligase modulator, targets acute myeloid leukemia blasts and leukemia stem cells. Blood. 2021 Feb 4;137(5):661-677. doi: 10.1182/blood.2020008676.

  PMID: 33197925 DERIVED

Related Links

• BMS Clinical Trial Information

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia

Interventions

CC-90009; venetoclax; Azacitidine; gilteritinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2020
• First Posted: April 7, 2020
• Study Start: August 5, 2020
• Primary Completion: October 25, 2023
• Study Completion: April 5, 2024
• Last Updated: May 31, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

BE (1); CA (2); GB (1); US (7); FR (3)