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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06137118




Registration number
NCT06137118
Ethics application status
Date submitted
3/11/2023
Date registered
18/11/2023
Date last updated
21/05/2024

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
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 will receive AZD0486 IV infusions and 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, C: Safety Evaluation of AZD0486
Timepoint [2] 0 0
From signing of informed consent through study completion, 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
First dose up to 36 months

Eligibility
Key inclusion criteria
- Age: 16 years and older (Part A), 12 years and older (Parts B and C).

- Participants with CD19+ B-cell Acute Lymphoblastic Leukemia 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.

- Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2
OR 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/Phase 2
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
4/02/2027
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
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
United States of America
State/province [7] 0 0
Virginia
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
United States of America
State/province [9] 0 0
Wisconsin
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
China
State/province [12] 0 0
Changsha
Country [13] 0 0
China
State/province [13] 0 0
Chengdu
Country [14] 0 0
China
State/province [14] 0 0
Guangzhou
Country [15] 0 0
China
State/province [15] 0 0
Hangzhou
Country [16] 0 0
China
State/province [16] 0 0
Nanjing
Country [17] 0 0
China
State/province [17] 0 0
Suzhou
Country [18] 0 0
China
State/province [18] 0 0
Zhengzhou
Country [19] 0 0
France
State/province [19] 0 0
Marseille
Country [20] 0 0
France
State/province [20] 0 0
Nantes
Country [21] 0 0
France
State/province [21] 0 0
Paris
Country [22] 0 0
France
State/province [22] 0 0
Pierre Bénite
Country [23] 0 0
Germany
State/province [23] 0 0
Essen
Country [24] 0 0
Germany
State/province [24] 0 0
Frankfurt A. Main
Country [25] 0 0
Germany
State/province [25] 0 0
Freiburg
Country [26] 0 0
Germany
State/province [26] 0 0
Halle
Country [27] 0 0
Germany
State/province [27] 0 0
Hamburg
Country [28] 0 0
Germany
State/province [28] 0 0
Köln
Country [29] 0 0
Germany
State/province [29] 0 0
Muenchen
Country [30] 0 0
Germany
State/province [30] 0 0
Münster
Country [31] 0 0
Germany
State/province [31] 0 0
Würzburg
Country [32] 0 0
Italy
State/province [32] 0 0
Bologna
Country [33] 0 0
Italy
State/province [33] 0 0
Monza
Country [34] 0 0
Italy
State/province [34] 0 0
Roma
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Seoul
Country [36] 0 0
Spain
State/province [36] 0 0
Barcelona
Country [37] 0 0
Spain
State/province [37] 0 0
Madrid
Country [38] 0 0
Spain
State/province [38] 0 0
Valencia
Country [39] 0 0
Taiwan
State/province [39] 0 0
Kaohsiung City
Country [40] 0 0
Taiwan
State/province [40] 0 0
Taichung
Country [41] 0 0
Taiwan
State/province [41] 0 0
Tainan City
Country [42] 0 0
Taiwan
State/province [42] 0 0
Taipei
Country [43] 0 0
United Kingdom
State/province [43] 0 0
London
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Manchester

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1/2, global multicentre, open-label, single-arm, dose escalation and dose
optimisation study of AZD0486 to evaluate the safety, tolerability, and efficacy of AZD0486
monotherapy in participants with R/R B ALL who have received = 2 prior lines of therapies.
The study will consist of 3 parts. Part A monotherapy dose escalation. Part B dose
optimisation. Part C Dose expansion at the recommended phase 2 dose (RP2D)
Trial website
https://clinicaltrials.gov/ct2/show/NCT06137118
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06137118