A Safety and Efficacy Study of CC-90009 Combinations in Subjects With Acute Myeloid Leukemia
- Adult subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
- Arm A (CC-90009 + venetoclax/azacitidine):
- Newly diagnosed AML and is ≥ 75 years of age or intensive chemotherapy ineligible OR
- Refractory AML and is ≥ 18 years of age
- Arm B (CC-90009 + gilteritinib):
- Subject is ≥ 18 years of age.
- FLT3-ITD positive relapsed or refractory AML.
- 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 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.
- Agree to follow the CC-90009 Pregnancy Prevention Plan (PPP) and combination agents' requirements.
- 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
- 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.
- 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. suspected during screening.
- Subject is a pregnant or lactating female
- Additional exclusion criteria based on combination agent:
- 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.
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)
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
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.
Trial Phase Phase I/II
Trial Type Treatment
- Primary ID CC-90009-AML-002
- Secondary IDs NCI-2020-03281, U1111-1247-5619, 2019-001681-15
- Clinicaltrials.gov ID NCT04336982