B-cell Acute Lymphoblastic Leukemia (B-ALL)Phase 1/2ALLightNCT07109219
Study of AZD4512 Monotherapy or in Combination With Anticancer Agents in Participants With Acute Lymphoblastic Leukemia
A Phase 1/2 study testing AZD4512 monotherapy in people with B-cell Acute Lymphoblastic Leukemia (B-ALL), run by AstraZeneca at 27 sites in 9 countries.
Trial summary
The study is intended to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of AZD4512 in patients with relapsed/refractory B-Cell acute lymphoblastic leukemia (r/r B-ALL). Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- B-cell Acute Lymphoblastic Leukemia (B-ALL)
- What is being tested?
- AZD4512 monotherapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 83 participants
- Where
- 27 sitesin 9 countries
- Study dates
- 12 Nov 2025to 18 Jul 2029
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 1. Age:
- 16 years old in Module 1 (US only: ≥18year)
- 12 years old in Module 2
- 2. Diagnosis: Known Diagnosis of CD22-positive B-ALL based on criteria established by WHO (Alaggio et al. 2022).
- All Participants must have relapsed or refractory B-ALL ('relapsed' defined as bone marrow blasts > 5% or reappearance of blasts in PB)
- Module 1 (DE): R/R B-ALL [Ph(-) and Ph(+)]
Show all 14Show fewer
- Backfill of Module 1 and Module 2 (DO): R/R B-ALL [Ph(-)] with demonstration of CD22 expression by local assessment in screening.
- 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. Prior therapies:
- Module 1 (DE): At least 2 prior therapies with refractoriness or relapse, or 1 prior therapy with refractoriness or relapse and no standard options available. For Ph+ B-ALL: 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
- Backfill of Module 1 (backfills) and Module 2 (DO): at least one prior line of therapy (SOC or clinical trial) to which the participant has been either refractory or has subsequently relapsed.
- Participants who have received prior CD22 targeted therapies and were not refractory to these therapies are eligible
- 6. Prior DLI >4 weeks, prior cell therapy or autoHSCT >8 weeks, alloHSCT >12 weeks
Who cannot join
- Burkitt lymphoma and leukemia
- Isolated extramedullary disease; Active testicular or CNS (> CNS1) involvement
- Unresolved non-heme toxicities Grade ≥ 2 (except alopecia, stable Grade ≤ 2 neuropathy, vitiligo, endocrine disorders controlled with therapy)
- 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
- Prior/concomitant therapy
- Cytotoxic treatment within 14 days (except ALL maintenance medications or cytoreduction)
Show all 12Show fewer
- 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 5 half-lives
- Strong inhibitors of CYP 3A4 within 14 days or 5 half-lives (whichever is longer)
- Investigational agents or study interventions in the last 30 days or 5 half-lives prior to the first dose of AZD4512 whichever is longer.
- If the investigational product is an agent to treat B-ALL and meets the modality criteria, then a specific washout period must be adhered to instead.
Trial locations and contacts
27 sites in 9 countries. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
27 sites in 9 countries
United States6 sites, 5 recruiting
- Recruiting
Research Site
Chicago, Illinois, 60611
- Recruiting
Research Site
Duarte, California, 91010
- Recruiting
Research Site
Franklin, Tennessee, 37067
- Recruiting
Research Site
Houston, Texas, 77030
- Recruiting
Research Site
Iowa City, Iowa, 52242
- Withdrawn
Research Site
Jacksonville, Florida, 32224
Spain5 sites, 4 recruiting
- Recruiting
Research Site
Badalona, 8916
- Recruiting
Research Site
Barcelona, 08035
- Recruiting
Research Site
Salamanca, 37007
- Recruiting
Research Site
Santander, 39008
- Withdrawn
Research Site
Valencia, 46026
South Korea4 sites, 4 recruiting
- Recruiting
Research Site
Seoul, 03080
- Recruiting
Research Site
Seoul, 06351
- Recruiting
Research Site
Seoul, 06591
- Recruiting
Research Site
Seoul, 3722
Japan3 sites, 3 recruiting
- Recruiting
Research Site
Bunkyō City, 113-8677
- Recruiting
Research Site
Chūōku, 104-0045
- Not yet recruiting
Research Site
Kashiwa, 277-8577
Canada2 sites, 2 recruiting
- Recruiting
Research Site
Toronto, Ontario, M5G 1X6
- Not yet recruiting
Research Site
Vancouver, British Columbia, V5Z 1M9
China2 sites, 2 recruiting
- Not yet recruiting
Research Site
Guangzhou, 510515
- Not yet recruiting
Research Site
Tianjin, 301600
Taiwan2 sites, 2 recruiting
- Recruiting
Research Site
Taichung, 40705
- Recruiting
Research Site
Taipei, 106
United Kingdom2 sites, 2 recruiting
- Recruiting
Research Site
Bloomsbury, W1T 7HA
- Recruiting
Research Site
Manchester, M20 4BX
About this study
Official 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
The study is intended to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of AZD4512 in patients with relapsed/refractory B-Cell acute lymphoblastic leukemia (r/r B-ALL).
Read the detailed description
In this Phase I/II, open-label multi-center study AZD4512 will be administered to adult/young adult patients (Module 1: >=16 years; Module 2: >=12 years) with relapsed/refractory B-Cell acute lymphoblastic leukemia (B-ALL). This study will have 2 parts: Module 1 - Dose Escalation and Module 2 - Dose Optimization.
- Being tested
- AZD4512 monotherapy
- Keywords
- Acute lymphoblastic leukemia (B-ALL), Dose escalation, Dose optimization, Cluster of differentiation 22 (CD22), Antibody-drug conjugate (ADC)
- Medical subject headings
- Burkitt Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD4512 monotherapyCombination product
Patients will receive AZD4512 as monotherapy via intravenous infusion. AZD4512 is an antibody-drug conjugate targeting CD22
| Study group | Role | What they receive |
|---|---|---|
| Module 1 Dose Escalation | Experimental | 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. Receives: Combination Product: AZD4512 monotherapy |
| Module 2 Dose Optimization | Experimental | 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. Receives: Combination Product: AZD4512 monotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Module 1 (Dose Escalation): Number of participants with dose-limiting toxicities (DLTs).
DLTs are dose-limiting toxicities as defined in the study protocol.
Measured: From first dose up to 21 days (DLT period).
Module 1 (Dose Escalation): Frequency, duration and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs)
Assessed by the CTCAE criteria version 5.0
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 1 (Dose Escalation): Frequency of dose interruptions, modifications, delays, and discontinuations due to AEs
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 1 (Dose Escalation): Number of participants with clinically significant changes in laboratory values, ECGs, performance status, and vital signs
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 2 (Dose Optimization): Overall response rate (ORR) in participants with R/R Ph(-) B-ALL
To evaluate the efficacy based on NCCN response criteria, measured by ORR (CR/CRh)
Measured: From date of first dose of AZD4512 up until end of study, up to 38 months
Module 2 (Dose Optimization): Frequency, duration and severity of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs)
Assessed by the CTCAE criteria version 5.0
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 2 (Dose Optimization): Frequency of dose interruptions, modifications, delays, and discontinuations due to AEs
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 2 (Dose Optimization): Number of participants with clinically significant changes in laboratory values, ECGs, performance status, and vital signs
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Secondary outcomes (34)
Module 1 (Dose Escalation): Plasma PK parameters of AZD4512
To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL.
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 1 (Dose Escalation): Total antibody and total unconjugated payload
To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL.
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 1 (Dose Escalation): Area Under Curve (AUC)
To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL.
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 1 (Dose Escalation): Peak Plasma Concentration (Cmax)
To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL.
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 1 (Dose Escalation): Time to max concentration (Tmax)
To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL.
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 1 (Dose Escalation): Half life (T1/2)
To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL.
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 1 (Dose Escalation): Clearance (CL)
To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL.
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 1 (Dose Escalation): Volume of distribution (Vz)
To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL.
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 1 (Dose Escalation): Number and percentage of participants who develop anti-drug antibodies (ADAs)
To determine the immunogenicity of AZD4512 as monotherapy in participants with R/R B-ALL.
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 1 (Dose Escalation): Objective Response Rate (ORR): proportion of participants with CR or CRh
To evaluate the preliminary efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines
Measured: From date of first dose of AZD4512 up until end of study, up to 38 months
Module 1 (Dose Escalation): Composite Complete Remission (CRc) rate: proportion of participants with CR, CRh, or CRi
To evaluate the preliminary efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines
Measured: From date of first dose of AZD4512 up until end of study, up to 38 months
Module 1 (Dose Escalation): Complete Remission (CR) rate
To evaluate the preliminary efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines
Measured: From date of first dose of AZD4512 up until end of study, up to 38 months
Module 1 (Dose Escalation): Time to Response (TTR)
To evaluate the preliminary efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines
Measured: From date of first dose of AZD4512 up until end of study, up to 38 months
Module 1 (Dose Escalation): Duration of Response (DoR)
- To evaluate the preliminary efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines
Measured: From date of first dose of AZD4512 up until end of study, up to 38 months
Module 1 (Dose Escalation): Event-Free Survival (EFS)
- To evaluate the preliminary efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines
Measured: From date of first dose of AZD4512 up until end of study, up to 38 months
Module 1 (Dose Escalation): Overall Survival (OS)
- To evaluate the preliminary efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines
Measured: From date of first dose of AZD4512 up until end of study, up to 38 months
Module 1 (Dose Escalation): Percentage of participants who receive subsequent allogeneic hematopoietic stem cell transplant (HSCT)
- To evaluate the preliminary efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-) and Ph(+)] as defined by NCCN guidelines
Measured: From date of first dose of AZD4512 up until end of study, up to 38 months
Module 2 (Dose Optimization): Complete Remission (CR) rate
To evaluate the efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)] as defined by NCCN guidelines
Measured: From date of first dose of AZD4512 up until end of study, up to 38 months
Module 2 (Dose Optimization):Composite Complete Remission (CRc) rate: proportion of participants with CR, CRh, or CRi
To evaluate the efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)] as defined by NCCN guidelines
Measured: From date of first dose of AZD4512 up until end of study, up to 38 months
Module 2 (Dose Optimization):Time to Response (TTR)
To evaluate the efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)] as defined by NCCN guidelines
Measured: From date of first dose of AZD4512 up until end of study, up to 38 months
Module 2 (Dose Optimization): Duration of Response (DoR)
To evaluate the efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)] as defined by NCCN guidelines
Measured: From date of first dose of AZD4512 up until end of study, up to 38 months
Module 2 (Dose Optimization):Event-Free Survival (EFS)
To evaluate the efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)] as defined by NCCN guidelines
Measured: From date of first dose of AZD4512 up until end of study, up to 38 months
Module 2 (Dose Optimization): Overall Survival (OS)
To evaluate the efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)] as defined by NCCN guidelines
Measured: From date of first dose of AZD4512 up until end of study, up to 38 months
Module 2 (Dose Optimization): Percentage of participants who receive subsequent allogeneic hematopoietic stem cell transplant (HSCT)
To evaluate the efficacy of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)] as defined by NCCN guidelines
Measured: From date of first dose of AZD4512 up until end of study, up to 38 months
Module 2 (Dose Optimization): MRD-negative CR rate, CR/CRh (ORR), CR/CRi/CRh (CRc) rate
To evaluate the impact of AZD4512 on MRD as assessed by NGS (central)
Measured: From date of first dose of AZD4512 up until end of study, up to 38 months
Module 2 (Dose Optimization): Plasma PK parameters of AZD4512
To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)]
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 2 (Dose Optimization): total antibody and total unconjugated payload
To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)]
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 2 (Dose Optimization): Area Under Curve (AUC)
To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)]
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 2 (Dose Optimzation): Peak Plasma Concentration (Cmax)
To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)]
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 2 (Dose Optimization): Time to max concentration (Tmax)
To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)]
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 2 (Dose Optimization): Half life (T1/2)
To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)]
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 2 (Dose Optimization): Clearance (CL)
To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)]
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 2 (Dose Optimization): Volume of distribution (Vz)
To characterize the PK of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)]
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Module 2 (Dose Optimization): Summary of of pre-existing and treatment induced ADAs for AZD4512 (positive or negative, titers)
To determine the immunogenicity of AZD4512 as monotherapy in participants with R/R B-ALL [Ph(-)]
Measured: From date of first dose of AZD4512 up until 30 days post last dose of AZD4512 (on average 6 months, maximum 12 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2025
- Study start12 Nov 2025
- Primary completion11 Oct 2028 (estimated)
- Study completion18 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B-cell Acute Lymphoblastic Leukemia (B-ALL)Studies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 83 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Fortrea
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07109219
- Sponsor's protocol ID
- D9891C00001
- Other IDs
- 2025-522372-93-00, 2025
- Acronym
- ALLight
- Status last verified
- Oct 2026
- First submitted
- 7 Jul 2025
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.