A Study to Assess the Safety, Tolerability, Pharmacokinetics of AZD0466 in Patients with Advanced Haematological Malignancies

Phase 1

• Conditions: Advanced Haematological Malignancies; MedDRA version: 20.0Level: LLTClassification code 10007051Term: Cancer (NOS)System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-005106-25-DE
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-10-05
• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 168

Inclusion Criteria

• Subjects must be aged =18 years inclusive, at the time of signing the informed consent. In some countries parental consent may be required in addition to an assent form for patients who are 18 years of age.
• Histologically confirmed acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL) or intermediate or higher risk myelodysplastic syndrome (MDS; Part A only) for which there are limited treatment options known to provide clinical benefit.
•Subjects must have received at least one prior line of therapy, and an established standard of care with proven benefit, and for which the patient is eligible, must not be available at the time of enrolment.
•Eastern Cooperative Oncology Group performance status =2. Performance status must not have deteriorated by =2 levels within 2 weeks after providing informed consent.
•Predicted life expectancy =8 weeks.
•White blood cell count must be <10 x 10^9/L prior to the first dose in Cycle 1, Day 1. Treatment with hydroxyurea (AML) or high-dose steroids (ALL and leukaemia of ambiguous lineage) during screening and Cycle 1 to control white blood cell count is permitted.
•Adequate organ function at screening as per the protocol defined criteria.
•Adequate cardiac function as demonstrated by LVEF > 50% on screening cardiac multigated acquisition, magnetic resonance image or echocardiogram.
•Willing and able to participate in all required study evaluations and procedures including receiving IV administration of study treatment and admission to the hospital, when required, for administration of study treatment and monitoring.
•For inclusion in the genetic component of the study, patients must fulfil protocol defined criteria.
•Women of childbearing potential and men should use protocol defined contraceptive measures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 68
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

•Unresolved toxicity from prior anticancer therapy of Common Terminology Criteria for Adverse Events Grade =2. Patients with Grade 2 neuropathy or Grade 2 alopecia are eligible.
•Active idiopathic thrombocytopenic purpura.
•Haemopoietic Stem cell transplant < 100 days prior to the first dose of study treatment.
• Immunosuppression for graft versus host disease (GVHD) or GVHD prophylaxis within 4 weeks prior to the first dose of study treatment. The following are permitted: (a) topical steroids for GVHD; (b) systemic steroids for GVHD up to 2 weeks prior to the first dose of study treatment; (c) treatment with high-dose steroids (ALL and leukaemia of ambiguous lineage) for white blood cell count control is permitted during screening, and in Cycle 1 up to 4 days.
•Active central nervous system (CNS) leukaemia/leptomeningeal disease/spinal cord compression. Patients who have a history of CNS leukaemia must be free of CNS leukaemia for >30 days prior to the first dose of study treatment, and the most recent 2 lumbar punctures must be negative for leukaemic cells, to be eligible.
• Known uncontrolled infection with cytomegalovirus.
•Active infection including human immunodeficiency virus, Hepatitis B, Hepatitis C, or severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).
•As judged by the Investigator: any evidence of severe or uncontrolled systemic diseases; current unstable or uncompensated respiratory or cardiac conditions; uncontrolled hypertension; history of, or active, bleeding diatheses (eg, haemophilia or von Willebrand disease); uncontrolled active systemic fungal, bacterial, or other infection.
•Any of the given cardiac criteria: subjects with history of myocarditis within one year of study entry, or heart failure New York Heart Association Functional Classification Class 3 or 4; mean resting corrected QT interval (QTcF) =470 msec obtained from 3 electrocardiograms (ECGs), in the absence of a cardiac pacemaker; abnormalities in rhythm, conduction or morphology of resting ECG; any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age.
•History of another life-threatening malignancy =2 years prior to first dose of study treatment. The following are permitted: myelodysplastic syndrome or myeloproliferative neoplasm (including chronic myelomonocytic leukaemia); malignancy treated with curative intent and with no evidence of active disease present; adequately treated lentigo malignant melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer; adequately treated carcinoma in situ without current evidence of disease.
•Any of the mentioned procedures or conditions currently or in the 6 months prior to the first dose of study treatment: coronary artery bypass graft; angioplasty; vascular stent; myocardial infarction; angina pectoris; haemorrhagic or thrombotic stroke, including transient ischaemic attacks or any other CNS bleeding.
• Treatment with any of the mentioned therapy: radiotherapy less than
3 weeks prior to first study treatment; anticancer agents within =14
days or 5 half-lives prior to the first dose of study treatment; Treatment
with high-dose steroids (ALL and leukaemia of ambiguous lineage) for
white blood cell count control is permitted during screening, and in Cycle
1 up to 4 days; subjects can continue to rece

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified