A Phase 2 Clinical Trial in Patients with AML version amend 4
Research type
Research Study
Full title
A Phase 2, Randomized, Biomarker-driven, Clinical Study in Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML) with an Exploratory Arm in Patients with Newly Diagnosed High-Risk AML
IRAS ID
228278
Contact name
Priyanka Mehta
Contact email
Sponsor organisation
Tolero Pharmaceuticals, Inc.
Eudract number
2017-001178-41
Clinicaltrials.gov Identifier
Duration of Study in the UK
4 years, 0 months, 0 days
Research summary
Alvocidib is a potent cyclin-dependent kinase (CDK) inhibitor with selectivity for CDKs 9, 1, 2, 4, and 7 with the greatest inhibition observed with CDK9. Overexpression of the myeloid leukemia cell-1 (MCL-1) has been shown to convey resistance to apoptosis induced by several different treatments. MCL-1 expression is down-regulated through the inhibition of CDK9 by alvocidib. Patients are pre-screened and selected for this clinical study based on their level of MCL-1 expression (NOXA BH3 priming). \nThe purpose of this research study is to determine the effectiveness and safety of alvocidib when used in combination with standard chemotherapy (cytarabine and mitoxantrone) in patients with previously treated acute myeloid leukemia (AML) who test positive at a certain level for NOXA priming (MCL-1 dependence). \nThere are 3 stages of the study: \nIn Stage 1 of the study, all eligible previously treated AML patients with demonstrated NOXA BH3 priming of ≥ 40% by mitochondrial profiling in bone marrow will receive treatment with alvocidib, cytarabine and mitoxantrone [ACM regimen].\nIn Stage 2, all eligible previously treated AML patients with demonstrated NOXA BH3 priming of ≥ 40% by mitochondrial profiling in bone marrow will be randomized 1:1 to receive either treatment with ACM or CM (cytarabine and mitoxantrone).\nIn the exploratory arm, all eligible patients with newly diagnosed high-risk AML with NOXA BH3 priming ≥40% by mitochondrial profiling in bone marrow will receive treatment with ACM. Additionally, previously treated AML patients with demonstrated NOXA BH3 priming of ≥ 30% to 39% by mitochondrial profiling in bone marrow will receive treatment with ACM.\nAbout 119 patients with AML will participate in this research study in the United States, Canada and Europe. Approximately 23 patients will be enrolled in Stage 1, 56 patients will be enrolled in Stage 2 and up to 20 patients in each of the Exploratory Arms.\n
REC name
South West - Central Bristol Research Ethics Committee
REC reference
17/SW/0174
Date of REC Opinion
10 Oct 2017
REC opinion
Further Information Favourable Opinion