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

Trial details

Who runs it

Celgene

Trial code

NCT04336982

Record updated

31 May 2024

Original description

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).Read full original descriptionShow less

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

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).

Inclusion: 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; Agree to follow the CC-90009 Pregnancy Prevention Plan (PPP) and combination agents' requirements.

Exclusion: 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 has persistent, clinically significant non-hematologic toxicities from prior therapies which have not recovered to < Grade 2; 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; Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to C1D1; 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; Previous SARS-CoV-2 vaccine within 14 days of C1D1; 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; 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; 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; Subject with acute promyelocytic leukemia (APL); 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; Subject is a pregnant or lactating female.

ClinicalTrials.gov NCT04336982