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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06137118




Registration number
NCT06137118
Ethics application status
Date submitted
3/11/2023
Date registered
18/11/2023

Titles & IDs
Public title
AZD0486 as Monotherapy in B-cell Acute Lymphoblastic Leukaemia
Scientific title
A Phase 1/2 Study to Evaluate the Safety and Efficacy of AZD0486 in Adolescent and Adult Participants With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukaemia
Secondary ID [1] 0 0
D7405C00001
Universal Trial Number (UTN)
Trial acronym
SYRUS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-cell Acute Lymphoblastic Leukemia (B-ALL) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AZD0486

Experimental: Part A: AZD0486 Dose Escalation - Ascending dose level cohorts of AZD0486 in B-ALL participants aged 16-80 years.

Experimental: Part B: Dose Optimization - Up to 2 cohorts will be evaluated prior declared safe-doses and schedules in order to determine the recommended phase 2 dose (RP2D). Participants, aged 12-80 years, will receive AZD0486 IV infusions and will be randomized in a 1:1 ratio.

Experimental: Part C: Dose Expansion - Part C will consist of 1 cohort of participants aged 12-80 years, treated with the optimal dose selected in Part B and receive IV AZD0486 monotherapy.


Treatment: Drugs: AZD0486
Investigational Product administered via intravenous infusion.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A: Frequency of DLTs
Timepoint [1] 0 0
28 days
Primary outcome [2] 0 0
Parts A & B: Safety Evaluation of AZD0486
Timepoint [2] 0 0
From signing of informed consent through completion of study treatment, an average of 8 months
Primary outcome [3] 0 0
Parts B & C: Overall Response Rate (ORR)
Timepoint [3] 0 0
From First dose to end of treatment or data cutoff, whichever comes first, assessed up to 24 months
Secondary outcome [1] 0 0
Part A: Objective Response Rate (ORR)
Timepoint [1] 0 0
From First dose to end of treatment or data cutoff, whichever comes first, assessed up to 12 months
Secondary outcome [2] 0 0
Parts A, B, C: Duration of response (DoR)
Timepoint [2] 0 0
Up to 36 months
Secondary outcome [3] 0 0
Parts A, B, C: CR rate at any time during the study
Timepoint [3] 0 0
From first dose until end of study, up to 36 months
Secondary outcome [4] 0 0
Parts A, B, C: Event-free survival (EFS)
Timepoint [4] 0 0
From first dose until end of study, up to 36 months
Secondary outcome [5] 0 0
Parts A, B, C: Overall survival (OS)
Timepoint [5] 0 0
From first dose until end of study, up to 36 months
Secondary outcome [6] 0 0
Parts B & C: Subsequent alloSCT
Timepoint [6] 0 0
From first dose until end of study, up to 24 months
Secondary outcome [7] 0 0
Parts B &C: CR MRD-negative rate
Timepoint [7] 0 0
First dose until end of study, up to 24 months
Secondary outcome [8] 0 0
Parts A, B, & C: PK characterization of AZD0486
Timepoint [8] 0 0
From first dose until end of study, up to 36 months
Secondary outcome [9] 0 0
Parts A, B & C: PK Characterization of AZD0486
Timepoint [9] 0 0
From first dose until end of study, up to 36 months
Secondary outcome [10] 0 0
Parts A, B, C: PK Characterization of AZD0486
Timepoint [10] 0 0
From first dose until end of study, up to 36 months
Secondary outcome [11] 0 0
Parts A, B, C: PK Characterization of AZD0486
Timepoint [11] 0 0
From first dose until end of study, up to 36 months
Secondary outcome [12] 0 0
Parts A, B, C: PK Characterization of AZD0486
Timepoint [12] 0 0
Pre-defined intervals from day 1 to day 28
Secondary outcome [13] 0 0
Parts A, B, C: PK Characterization of AZD0486
Timepoint [13] 0 0
From first dose until end of study, up to 36 months
Secondary outcome [14] 0 0
Parts A, B, C: ADA characterization of AZD0486
Timepoint [14] 0 0
Consent until 36 months after first dose
Secondary outcome [15] 0 0
Part C: Safety Evaluation of AZD0486
Timepoint [15] 0 0
From signing of informed consent through completion of study treatment, an average of 8 months

Eligibility
Key inclusion criteria
* Age: 16 years and older (Part A), 12 years and older (Parts B and C).
* Participants with B-cell Acute Lymphoblastic Leukemia with CD19 expression by local lab with:

1. Bone marrow infiltration with >/= 5% blasts
2. Either relapsed or refractory after a minimum of 2 prior therapies or after 1 prior line of therapy if no SOC available option.
3. Philadelphia positive participants are allowed in Part A if intolerant or refractory to TKIs.
* For participants older than 16 years, Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2. For Participants 16 years or younger, Lansky score more or equal to 50%.

The above is a summary, other inclusion criteria details may apply.
Minimum age
12 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Active CNS involvement by B-ALL, defined by presence of ALL blasts in CSF (CNS2 and CNS3 criteria).
* Isolated extramedullary disease relapse.
* Testicular leukemia
* History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis; or prior Grade 4 neurotoxicity with CAR-T or TCE therapy.
* History of other malignancy (with certain exceptions).
* Unresolved AEs >/= Grade 2, from prior therapies
* Prior therapy with TCEs within 4 weeks, CAR T-cell therapy or autologous HSCT within 8 weeks or prior alloSCT within 12 weeks of start of therapy.
* GVHD requiring immunosuppressive therapy within 3 weeks prior to AZD0486 treatment.

The above is a summary, other exclusion criteria details may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
29/06/2027
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington
Country [10] 0 0
United States of America
State/province [10] 0 0
Wisconsin
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
Canada
State/province [12] 0 0
Quebec
Country [13] 0 0
China
State/province [13] 0 0
Changsha
Country [14] 0 0
China
State/province [14] 0 0
Chengdu
Country [15] 0 0
China
State/province [15] 0 0
Guangzhou
Country [16] 0 0
China
State/province [16] 0 0
Hangzhou
Country [17] 0 0
China
State/province [17] 0 0
Nanjing
Country [18] 0 0
China
State/province [18] 0 0
Suzhou
Country [19] 0 0
China
State/province [19] 0 0
Zhengzhou
Country [20] 0 0
France
State/province [20] 0 0
Caen
Country [21] 0 0
France
State/province [21] 0 0
Marseille
Country [22] 0 0
France
State/province [22] 0 0
Nantes
Country [23] 0 0
France
State/province [23] 0 0
Paris
Country [24] 0 0
France
State/province [24] 0 0
Pierre Bénite
Country [25] 0 0
France
State/province [25] 0 0
Toulouse
Country [26] 0 0
Germany
State/province [26] 0 0
Essen
Country [27] 0 0
Germany
State/province [27] 0 0
Frankfurt
Country [28] 0 0
Germany
State/province [28] 0 0
Freiburg
Country [29] 0 0
Germany
State/province [29] 0 0
Halle
Country [30] 0 0
Germany
State/province [30] 0 0
Hamburg
Country [31] 0 0
Germany
State/province [31] 0 0
Köln
Country [32] 0 0
Germany
State/province [32] 0 0
München
Country [33] 0 0
Germany
State/province [33] 0 0
Münster
Country [34] 0 0
Germany
State/province [34] 0 0
Wuerzburg
Country [35] 0 0
Italy
State/province [35] 0 0
Bologna
Country [36] 0 0
Italy
State/province [36] 0 0
Monza
Country [37] 0 0
Italy
State/province [37] 0 0
Roma
Country [38] 0 0
Japan
State/province [38] 0 0
Chuo-ku
Country [39] 0 0
Japan
State/province [39] 0 0
Kyoto-shi
Country [40] 0 0
Japan
State/province [40] 0 0
Osaka-shi
Country [41] 0 0
Korea, Republic of
State/province [41] 0 0
Seoul
Country [42] 0 0
Spain
State/province [42] 0 0
Barcelona
Country [43] 0 0
Spain
State/province [43] 0 0
Madrid
Country [44] 0 0
Spain
State/province [44] 0 0
Valencia
Country [45] 0 0
Taiwan
State/province [45] 0 0
Kaohsiung City
Country [46] 0 0
Taiwan
State/province [46] 0 0
Taichung
Country [47] 0 0
Taiwan
State/province [47] 0 0
Tainan City
Country [48] 0 0
Taiwan
State/province [48] 0 0
Taipei
Country [49] 0 0
United Kingdom
State/province [49] 0 0
London
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Manchester
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Surrey

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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
information.center@astrazeneca.com
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 request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
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 rerefer 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 patient-level 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/NCT06137118