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

NCT ID: NCT04336982

Last Updated: 2024-05-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-05
• Study Completion Date: 2024-04-05

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).

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.

Conditions

Leukemia, Myeloid, Acute

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

CC-90009

Intervention Type: DRUG

Injection

Venetoclax

Intervention Type: DRUG

Tablet

Azacitidine

Intervention Type: DRUG

Injection

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.

Group Type: EXPERIMENTAL

Gilteritinib

Intervention Type: DRUG

Tablet

Interventions

CC-90009

Injection

Intervention Type: DRUG

Venetoclax

Tablet

Intervention Type: DRUG

Azacitidine

Injection

Intervention Type: DRUG

Gilteritinib

Tablet

Intervention Type: DRUG

Eligibility 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 either ≥ 75 years of age or is ineligible for intensive chemotherapy OR

2. Part A: Primary Refractory AML, or AML in first relapse, 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 ≥ 30 mL/min.

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: collaborator

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Local Institution - 104

San Francisco, California, United States

Local Institution - 107

New Haven, Connecticut, United States

Local Institution - 103

Boston, Massachusetts, United States

Local Institution - 101

St Louis, Missouri, United States

Local Institution - 108

Hackensack, New Jersey, United States

Local Institution - 105

Houston, Texas, United States

Local Institution - 102

Seattle, Washington, United States

Local Institution - UNK3

Yvoir, , Belgium

Local Institution - 202

Edmonton, Alberta, Canada

Local Institution - 201

Toronto, Ontario, Canada

Local Institution - 402

Marseille, , France

Local Institution - 401

Pessac, , France

Local Institution - 404

Toulouse, , France

Local Institution - 301

Oxford, , United Kingdom

Countries

United States; Belgium; Canada; France; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 33197925 (View on PubMed)

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

Other Identifiers

U1111-1247-5619

Identifier Type: OTHER

Identifier Source: secondary_id

2019-001681-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CC-90009-AML-002

Identifier Type: -

Identifier Source: org_study_id