Leukemia, Myeloid, Acute
Conditions
Keywords
CC-90009, Venetoclax, Azacitidine, Gilteritinib, Hematologic cancers, Leukemia, Acute myeloid leukemia, AML
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.
Interventions
Sponsors
AbbVie
Celgene
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 11. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicity (DLT) | Up to 28 days | Number of participants with a DLT |
| Adverse Events (AEs) | 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
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | 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 |
| Overall Survival (OS) | 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. |
| Duration of Remission | 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. |
| Complete Remission Rate (CRR), | Up to 3 years | is defined as the rate for any type of CR or CRh |
| Pharmacokinetics - Cmax | 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 |
| Pharmacokinetics - AUC24 | 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 |
| Pharmacokinetics - t1/2 | 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 |
| Time to Remission | Up to 3 years | is measured from the time when criteria for CR/CRh/PR are first met (whichever is first recorded) |
| Objective Response Rate (ORR) | Up to 3 years | includes all responses of complete remissions (CRs), Morphologic leukemia-free state (MLFS), and Partial remission (PR) |
Countries
Belgium, Canada, France, United Kingdom, United States
Outcome results
None listed