Study of AZD0466 Monotherapy or in Combination in Patients With Advanced Haematological Malignancies

Overview

About this study

The purpose of the study is to the evaluate safety, tolerability, pharmacokinetics (PK), and effectiveness of AZD0466 as monotherapy in participants with advanced haematological malignancies,  and also to assess drug-drug interaction (DDI) potential between AZD0466 and the azole antifungal voriconazole.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

- Diagnosis of acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL), or
intermediate or higher risk myelodysplastic syndrome (MDS; Part A only), which is
histologically proven based on criteria established by the World Health Organization
(WHO) as documented by medical records. for which there are limited treatment options
known to provide clinical benefit.

- 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.

- 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, participants must fulfil protocol
defined criteria.

- White blood cell count must be <10 x 10^9/L prior to the first dose in Cycle 1, Day 1.
Treatment with hydroxyurea during screening and Cycle 1 to control white blood cell
count is permitted.

- Women of childbearing potential and men should use protocol defined contraceptive
measures.

Exclusion Criteria:

- Unresolved toxicity from prior anticancer therapy of Common Terminology Criteria for
Adverse Events Grade ≥2. Participants with Grade 2 neuropathy or Grade 2 alopecia are
eligible.

- Active idiopathic thrombocytopenic purpura.

- 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.

- Active central nervous system (CNS) leukaemia/leptomeningeal disease/spinal cord
compression. Participants 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 (CMV) infection (positive CMV
Immunoglobulin M (IgM) and/or positive polymerase chain reaction (PCR) result).

- 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, (eg, severe hepatic impairment, interstitial lung disease [bilateral,
diffuse, parenchymal lung disease]); 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: 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
electrocardiogram (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 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 [CMML]); malignancy treated with
curative intent and with no evidence of active disease present for more than 2 years
before screening and considered to be at low risk of recurrence by the treating
physician; 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; chemotherapy within ≤14 days or 5 half-lives prior to the first
dose of study treatment. Treatment with high-dose steroids for primary malignancy
control is permitted but must be discontinued at least 2 days prior to the first dose
of study treatment. Treatment with hydroxyurea is permitted; immunotherapies and
cellular therapies within 4 weeks prior to the first dose of study treatment;
investigational drugs within ≤14 days or 5 half-lives (whichever is shorter) prior to
the first dose of study treatment; major surgery (excluding placement of vascular
access) ≤21 days, or minor surgical procedures ≤7 days, prior to the first dose of
study treatment. No waiting is required mentioned implantable port or catheter
placement; prescription or non-prescription drugs or other products known to be
sensitive substrates of BCRP, OCT2, OAT3, OATP1B1, OATP1B3, CYP2B6, CYP2C8, CYP2C9 or
CYP2D6, or reversible moderate or strong CYP3A inhibitors, which cannot be
discontinued within 5 half-lives prior to the first dose of study treatment and
withheld throughout the study until 14 days after the last dose of AZD0466; moderate
or strong mechanism-based inhibitors or inducers of CYP3A4 which cannot be
discontinued within 5 half-lives plus of the specific drug 12 days of the drug prior
to the first dose of study treatment and withheld until 14 days after the last dose of
AZD0466; concurrent anti-coagulation therapy, including aspirin and heparin, which
cannot be stopped; medications with known risk of Torsades de Pointes which cannot be
discontinued within 5 half-lives of the first dose of study treatment and withheld
until 14 days after the last dose of AZD0466; IV anti infection treatment within 14
days before first dose of study treatment.

- History of hypersensitivity to polyethylene glycol (PEG), PEGylated products or drugs
with a similar chemical structure or class to AZD0466 or other BH3 mimetic.

Module 2:

? Patients for whom treatment with voriconazole is contraindicated per the local
prescribing information must not enter the study.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 12/20/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Talha Badar, M.B.B.S., M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Cecilia Arana Yi, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available
.
CLS-20531310

Mayo Clinic Footer