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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04865419




Registration number
NCT04865419
Ethics application status
Date submitted
26/04/2021
Date registered
29/04/2021

Titles & IDs
Public title
Study of AZD0466 Monotherapy or in Combination in Patients With Advanced Haematological Malignancies
Scientific title
A Modular Phase I/II, Open-Label, Multi-Centre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AZD0466 Monotherapy or in Combination in Patients With Advanced Haematological Malignancies
Secondary ID [1] 0 0
2020-005106-25
Secondary ID [2] 0 0
D8241C00001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Haematological Malignancies 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AZD0466
Treatment: Drugs - Voriconazole

Experimental: Module 1: AZD0466 monotherapy - Participants will receive intravenous infusion of AZD0466 monotherapy once weekly during Cycle 1 (35 days), Cycle 2 (28 days) and Cycle 3 (28 days) and also beyond Cycle 3 until progressive disease, unacceptable toxicity, or withdrawal of consent.

Experimental: Module 2: AZD0466 + Voriconazole - Participants may receive IV infusion of AZD0466 in combination with or without voriconazole during Cycle 1 (21 days), and Cycle 2 (28 days) and Cycle 3 (28 days) and also beyond Cycle 3 until progressive disease, unacceptable toxicity, or withdrawal of consent.


Treatment: Drugs: AZD0466
AZD0466 powder for concentrate for solution for infusion will be administered by IV infusion.

Treatment: Drugs: Voriconazole
Voriconazole film-coated tablet will be administered orally.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with adverse events (AEs) and serious adverse events (SAEs) [Module 1]
Timepoint [1] 0 0
Until 28 days after last dose (Upto 3.5 Years)
Primary outcome [2] 0 0
Number of participants with adverse events (AEs) and serious adverse events (SAEs) [Module 2]
Timepoint [2] 0 0
Until Day 19
Primary outcome [3] 0 0
Number of participants with Dose-limiting toxicity (DLT) [Module 1]
Timepoint [3] 0 0
35 days
Secondary outcome [1] 0 0
Module 1: Complete Response Rate (CR+CRi)
Timepoint [1] 0 0
Day 1 until post treatment follow-up (28 days after last dose) (up to 3.5 Years)
Secondary outcome [2] 0 0
Module 1: Time to Response (TTR)
Timepoint [2] 0 0
Day 1 until post treatment follow-up (28 days after last dose) (up to 3.5 Years)
Secondary outcome [3] 0 0
Module 1: Duration of Response (DoR)
Timepoint [3] 0 0
Day 1 until post treatment follow-up (28 days after last dose) (up to 3.5 Years)
Secondary outcome [4] 0 0
Module 1: Overall Survival (OS)
Timepoint [4] 0 0
Day 1 until post treatment follow-up (28 days after last dose) and survival follow-up (every month after last dose) (up to 3.5 Years)
Secondary outcome [5] 0 0
Module 2: Area under the plasma concentration-curve (AUC) of AZD4320 after administration of AZD0466 alone and in combination with voriconazole
Timepoint [5] 0 0
Cycle 1 Days 1, 2, 3, 4, 8 and days 15, 16, 17, 18, 19, and Cycle 2 Day 1, Cycle 3 Day 1 and beyond (Cycle length 28-days) (up to 3.5 Years)
Secondary outcome [6] 0 0
Module 2: Maximum observed plasma (peak) drug concentration (Cmax) of AZD4320 after administration of AZD0466 alone and in combination with voriconazole
Timepoint [6] 0 0
Cycle 1: Days 1, 2, 3, 4, 8 and days 15, 16, 17, 18, 19, and Cycle 2 Day 1, Cycle 3 Day 1 and beyond (Cycle length 28-days) (up to 3.5 Years)
Secondary outcome [7] 0 0
Module 1 and Module 2: Plasma concentration of AZD4320
Timepoint [7] 0 0
Module 1: Cycle 1 Days 1-30 (Cycle length 21 days) to Cycle 3 Days 1-28, and beyond (Cycle length 28 days); Module 2: Cycle 1 Days 1-8, Days 15-19 (Cycle length 21 days), Cycle 2 Day 1, Cycle 3 Day 1 and beyond (Cycle length 28-days) (up to 3.5 Years)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/06/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/08/2023
Sample size
Target
Accrual to date
Final
46
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Melbourne
Recruitment hospital [2] 0 0
Research Site - Parkville
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
France
State/province [6] 0 0
Pessac
Country [7] 0 0
Germany
State/province [7] 0 0
Aachen
Country [8] 0 0
Germany
State/province [8] 0 0
Heidelberg
Country [9] 0 0
Germany
State/province [9] 0 0
Kiel
Country [10] 0 0
Italy
State/province [10] 0 0
Bologna
Country [11] 0 0
Italy
State/province [11] 0 0
Meldola
Country [12] 0 0
Italy
State/province [12] 0 0
Rozzano
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Busan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Nitin Jain, MD, PhD
Address 0 0
The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard, Unit 431 Houston, Texas 77030 United States of America
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
When will data be available (start and end dates)?
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at:

https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.
Available to whom?
When a request has been approved AstraZeneca will provide access to the de-identified individual patientlevel data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at:

https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04865419