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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT07109219




Registration number
NCT07109219
Ethics application status
Date submitted
7/07/2025
Date registered
7/08/2025
Date last updated
7/08/2025

Titles & IDs
Public title
Study of AZD4512 Monotherapy or in Combination With Anticancer Agents in Participants With Acute Lymphoblastic Leukemia
Scientific title
A Modular Phase I/II, Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Preliminary Efficacy of AZD4512 Monotherapy or in Combination With Anticancer Agent(s) in Participants With Acute Lymphoblastic Leukemia
Secondary ID [1] 0 0
2025-522372-93-00
Secondary ID [2] 0 0
D9891C00001
Universal Trial Number (UTN)
Trial acronym
ALLight
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
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - AZD4512 monotherapy

Experimental: Module 1 Dose Escalation - Module 1 will evaluate escalating doses of AZD4512 as monotherapy to determine the maximum tolerated dose (MTD) and/or doses of AZD4512 for subsequent evaluation in Module 2 (dose optimization), in participants with relapsed/refractory (R/R) Philadelphia chromosome positive (Ph\[+\]) and negative (Ph\[-\]) B-ALL, R/R as defined by National Comprehensive Cancer Network (NCCN) guidelines, or with measurable residual disease (MRD) = 1% to = 5% after failing or relapsing after standard of care therapies.

Experimental: Module 2 Dose Optimization - Module 2 will randomize participants with R/R (as defined by NCCN guidelines) Ph(-) BALL only across 2 to 3 dose levels identified in Module 1 to receive AZD4512 monotherapy for further exploration of the doses. The aim of Module 2 is to identify the recommended Phase 2 dose (RP2D) of AZD4512 monotherapy, evaluate the efficacy and further define the safety profile of AZD4512.


Other interventions: AZD4512 monotherapy
Patients will receive AZD4512 as monotherapy via intravenous infusion. AZD4512 is an antibody-drug conjugate targeting CD22

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Module 1 (Dose Escalation): Number of participants with dose-limiting toxicities (DLTs).
Timepoint [1] 0 0
From first dose up to 21 days (DLT period).
Primary outcome [2] 0 0
Module 1 (Dose Escalation): Frequency, duration and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs)
Timepoint [2] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Primary outcome [3] 0 0
Module 1 (Dose Escalation): Frequency of dose interruptions, modifications, delays, and discontinuations due to AEs
Timepoint [3] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Primary outcome [4] 0 0
Module 1 (Dose Escalation): Number of participants with clinically significant changes in laboratory values, ECGs, performance status, and vital signs
Timepoint [4] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Primary outcome [5] 0 0
Module 2 (Dose Optimization): Overall response rate (ORR) in participants with R/R Ph(-) B-ALL
Timepoint [5] 0 0
From date of first dose of AZD4512 up until end of study, up to 38 months
Primary outcome [6] 0 0
Module 2 (Dose Optimization): Frequency, duration and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs)
Timepoint [6] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Primary outcome [7] 0 0
Module 2 (Dose Optimization): Frequency of dose interruptions, modifications, delays, and discontinuations due to AEs
Timepoint [7] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Primary outcome [8] 0 0
Module 2 (Dose Optimization): Number of participants with clinically significant changes in laboratory values, ECGs, performance status, and vital signs
Timepoint [8] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Secondary outcome [1] 0 0
Module 1 (Dose Escalation): Plasma PK parameters of AZD4512
Timepoint [1] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Secondary outcome [2] 0 0
Module 1 (Dose Escalation): Total antibody and total unconjugated payload
Timepoint [2] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Secondary outcome [3] 0 0
Module 1 (Dose Escalation): Area Under Curve (AUC)
Timepoint [3] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Secondary outcome [4] 0 0
Module 1 (Dose Escalation): Peak Plasma Concentration (Cmax)
Timepoint [4] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Secondary outcome [5] 0 0
Module 1 (Dose Escalation): Time to max concentration (Tmax)
Timepoint [5] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Secondary outcome [6] 0 0
Module 1 (Dose Escalation): Half life (T1/2)
Timepoint [6] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Secondary outcome [7] 0 0
Module 1 (Dose Escalation): Clearance (CL)
Timepoint [7] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Secondary outcome [8] 0 0
Module 1 (Dose Escalation): Volume of distribution (Vz)
Timepoint [8] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Secondary outcome [9] 0 0
Module 1 (Dose Escalation): Number and percentage of participants who develop anti-drug antibodies (ADAs)
Timepoint [9] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Secondary outcome [10] 0 0
Module 1 (Dose Escalation): Objective Response Rate (ORR): proportion of participants with CR or CRh
Timepoint [10] 0 0
From date of first dose of AZD4512 up until end of study, up to 38 months
Secondary outcome [11] 0 0
Module 1 (Dose Escalation): Composite Complete Remission (CRc) rate: proportion of participants with CR, CRh, or CRi
Timepoint [11] 0 0
From date of first dose of AZD4512 up until end of study, up to 38 months
Secondary outcome [12] 0 0
Module 1 (Dose Escalation): Complete Remission (CR) rate
Timepoint [12] 0 0
From date of first dose of AZD4512 up until end of study, up to 38 months
Secondary outcome [13] 0 0
Module 1 (Dose Escalation): Time to Response (TTR)
Timepoint [13] 0 0
From date of first dose of AZD4512 up until end of study, up to 38 months
Secondary outcome [14] 0 0
Module 1 (Dose Escalation): Duration of Response (DoR)
Timepoint [14] 0 0
From date of first dose of AZD4512 up until end of study, up to 38 months
Secondary outcome [15] 0 0
Module 1 (Dose Escalation): Event-Free Survival (EFS)
Timepoint [15] 0 0
From date of first dose of AZD4512 up until end of study, up to 38 months
Secondary outcome [16] 0 0
Module 1 (Dose Escalation): Overall Survival (OS)
Timepoint [16] 0 0
From date of first dose of AZD4512 up until end of study, up to 38 months
Secondary outcome [17] 0 0
Module 1 (Dose Escalation): Percentage of participants who receive subsequent allogeneic hematopoietic stem cell transplant (HSCT)
Timepoint [17] 0 0
From date of first dose of AZD4512 up until end of study, up to 38 months
Secondary outcome [18] 0 0
Module 1 (Dose Escalation): MRD conversion rate: proportion of participants with conversion to MRD negativity (<10-4)
Timepoint [18] 0 0
From date of first dose of AZD4512 up until end of study, up to 38 months
Secondary outcome [19] 0 0
Module 1 (Dose Escalation): Time to MRD conversion
Timepoint [19] 0 0
From date of first dose of AZD4512 up until end of study, up to 38 months
Secondary outcome [20] 0 0
Module 2 (Dose Optimization): Complete Remission (CR) rate
Timepoint [20] 0 0
From date of first dose of AZD4512 up until end of study, up to 38 months
Secondary outcome [21] 0 0
Module 2 (Dose Optimization):Composite Complete Remission (CRc) rate: proportion of participants with CR, CRh, or CRi
Timepoint [21] 0 0
From date of first dose of AZD4512 up until end of study, up to 38 months
Secondary outcome [22] 0 0
Module 2 (Dose Optimization):Time to Response (TTR)
Timepoint [22] 0 0
From date of first dose of AZD4512 up until end of study, up to 38 months
Secondary outcome [23] 0 0
Module 2 (Dose Optimization): Duration of Response (DoR)
Timepoint [23] 0 0
From date of first dose of AZD4512 up until end of study, up to 38 months
Secondary outcome [24] 0 0
Module 2 (Dose Optimization):Event-Free Survival (EFS)
Timepoint [24] 0 0
From date of first dose of AZD4512 up until end of study, up to 38 months
Secondary outcome [25] 0 0
Module 2 (Dose Optimization): Overall Survival (OS)
Timepoint [25] 0 0
From date of first dose of AZD4512 up until end of study, up to 38 months
Secondary outcome [26] 0 0
Module 2 (Dose Optimization): Percentage of participants who receive subsequent allogeneic hematopoietic stem cell transplant (HSCT)
Timepoint [26] 0 0
From date of first dose of AZD4512 up until end of study, up to 38 months
Secondary outcome [27] 0 0
Module 2 (Dose Optimization): MRD-negative CR rate, CR/CRh (ORR), CR/CRi/CRh (CRc) rate
Timepoint [27] 0 0
From date of first dose of AZD4512 up until end of study, up to 38 months
Secondary outcome [28] 0 0
Module 2 (Dose Optimization): Plasma PK parameters of AZD4512
Timepoint [28] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Secondary outcome [29] 0 0
Module 2 (Dose Optimization): total antibody and total unconjugated payload
Timepoint [29] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Secondary outcome [30] 0 0
Module 2 (Dose Optimization): Area Under Curve (AUC)
Timepoint [30] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Secondary outcome [31] 0 0
Module 2 (Dose Optimzation): Peak Plasma Concentration (Cmax)
Timepoint [31] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Secondary outcome [32] 0 0
Module 2 (Dose Optimization): Time to max concentration (Tmax)
Timepoint [32] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Secondary outcome [33] 0 0
Module 2 (Dose Optimization): Half life (T1/2)
Timepoint [33] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Secondary outcome [34] 0 0
Module 2 (Dose Optimization): Clearance (CL)
Timepoint [34] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Secondary outcome [35] 0 0
Module 2 (Dose Optimization): Volume of distribution (Vz)
Timepoint [35] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)
Secondary outcome [36] 0 0
Module 2 (Dose Optimization): Summary of of pre-existing and treatment induced ADAs for AZD4512 (positive or negative, titers)
Timepoint [36] 0 0
From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months)

Eligibility
Key inclusion criteria
* 1. Age:

* 16 years old in Module 1
* 12 years old in Module 2

2. Diagnosis: Diagnosis of B-ALL WHO (WHO-HAEM5)
* Participants must have relapsed or refractory B-ALL ('relapsed' defined as bone marrow blasts > 5% or reappearance of blasts in PB) or R/R with MRD = 1% to =5%
* The nº of enrolled participants with MRD = 1 to = 5% will be limited to 25% of the DE cohort
* Module 1 (DE): Ph(-) B-ALL and Ph(+) B-ALL - R/R or with MRD = 1% to =5%
* Backfill of Module 1 and Module 2 (DO): R/R Ph(-) B-ALL (BM blasts >5%)

3. Performance status (ECOG = 2; KPS = 50; LPS = 50)

4. Peripheral lymphoblast count < 10,000/µL (may receive cytoreduction prior to C1D1 per protocol-specified criteria)

5. At least 2 prior therapies with refractoriness or relapse, or 1 prior therapy with refractoriness or relapse and no standard options available
* Ph+ B-ALL (Module 1 DE only): intolerant to or have contraindications to TKI therapy or R/R disease despite treatment with at least 2 prior TKIs or at least one 3rd generation TKI

6. Prior DLI >4 weeks, prior cell therapy or autoHSCT >8 weeks, alloHSCT >12 weeks
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Burkitt lymphoma and leukemia
2. Isolated extramedullary disease; Active testicular or CNS (> CNS1) involvement
3. Unresolved non-heme toxicities Grade = 2 (except alopecia, stable Grade = 2 neuropathy, vitiligo, endocrine disorders controlled with therapy)
4. History of drug-induced non-infectious ILD/pneumonitis requiring oral or IV steroids or supplemental oxygen or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
5. Prior/concomitant therapy

* Cytotoxic treatment within 14 days (except ALL maintenance medications or cytoreduction)
* Biologic (immuno-oncology) treatment within 28 days or 5 half-lives (whichever is shorter)
* Non-CNS radiation within 2 weeks & CNS radiation within 4 weeks
* Medications known to prolong QTc and/or associated with Torsades de Pointes within 21 days or 5 half-lives (whichever is longer)
* Strong inhibitors of CYP 3A4 within 21 days or 5 half-lives (whichever is longer)
* Investigational agents or study interventions in the last 30 days

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

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
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
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Iowa
Country [3] 0 0
United States of America
State/province [3] 0 0
Tennessee
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
Country [6] 0 0
Japan
State/province [6] 0 0
Bunkyo City
Country [7] 0 0
South Korea
State/province [7] 0 0
Seoul
Country [8] 0 0
Spain
State/province [8] 0 0
Barcelona
Country [9] 0 0
Spain
State/province [9] 0 0
Salamanca
Country [10] 0 0
Spain
State/province [10] 0 0
Santander
Country [11] 0 0
Spain
State/province [11] 0 0
Valencia
Country [12] 0 0
Taiwan
State/province [12] 0 0
Taichung
Country [13] 0 0
Taiwan
State/province [13] 0 0
Taipei
Country [14] 0 0
United Kingdom
State/province [14] 0 0
London
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Fortrea
Address [1] 0 0
Country [1] 0 0

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
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 Vivli.org. 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.

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 PhRMA 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 anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/


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.