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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06564038




Registration number
NCT06564038
Ethics application status
Date submitted
19/08/2024
Date registered
21/08/2024
Date last updated
8/09/2025

Titles & IDs
Public title
A Study of AZD0486 Monotherapy or in Combination With Other Anti-Cancer Agents for Mature B-Cell Malignancies
Scientific title
A Phase I/II Open-Label Multi-Centre Master Protocol to Evaluate the Safety and Efficacy of AZD0486 Monotherapy or in Combination With Other Anticancer Agents in Participants With Mature B-Cell Malignancies
Secondary ID [1] 0 0
2024-515034-33-00
Secondary ID [2] 0 0
D7407C00001
Universal Trial Number (UTN)
Trial acronym
Soundtrack-E
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukaemia 0 0
Small Lymphocytic Lymphoma 0 0
Mantle-cell Lymphoma 0 0
Large B-cell Lymphoma 0 0
B-cell Non-Hodgkin Lymphoma 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
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
Treatment: Drugs - Prednisone (or equivalent)
Treatment: Drugs - Rituximab
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Vincristine
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Acalabrutinib

Experimental: Substudy 1 (RR CLL/SLL): Cohort 1A (AZD0486 Monotherapy) - Participants will receive AZD0486 monotherapy as subcutaneous (SC) injection.

Experimental: Substudy 1 (RR CLL/SLL): Cohort 1B (AZD0486 + Acalabrutinib) - Participants will receive AZD0486 as SC injection. Participants will receive acalabrutinib tablet orally twice daily.

Experimental: Substudy 1 (RR CLL/SLL): Cohort 1C (AZD0486 Monotherapy) - Participants will receive AZD0486 monotherapy as intravenous (IV) infusion.

Experimental: Substudy 2 (RR MCL): Cohort 2A (AZD0486 Monotherapy) - Participants will receive AZD0486 monotherapy as SC injection.

Experimental: Substudy 2 (RR MCL): Cohort 2C (AZD0486 Monotherapy) - Participants will receive AZD0486 monotherapy as IV infusion.

Experimental: Substudy 3 (LBCL): AZD0486 + R-CHOP - Participants will receive AZD0486 as IV infusion in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy.


Treatment: Drugs: AZD0486
AZD0486 will be administered as either SC injection or IV infusion.

Treatment: Drugs: Prednisone (or equivalent)
Prednisone (or equivalent) will be administered either oral or IV infusion as per standard of care.

Treatment: Drugs: Rituximab
Rituximab will be administered as IV infusion as per standard of care.

Treatment: Drugs: Cyclophosphamide
Cyclophosphamide will be administered as IV infusion as per standard of care.

Treatment: Drugs: Vincristine
Vincristine will be administered as IV infusion as per standard of care.

Treatment: Drugs: Doxorubicin
Doxorubicin will be administered as IV infusion as per standard of care.

Treatment: Drugs: Acalabrutinib
Acalabrutinib 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, Serious Adverse Events and Adverse Events of Special Interest
Timepoint [1] 0 0
Up to 6 years 4 months
Primary outcome [2] 0 0
Number of Participants with Dose Limiting Toxicity (DLTs)
Timepoint [2] 0 0
Up to 2 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
Up to 6 years 4 months
Secondary outcome [2] 0 0
Complete Response (CR) Rate
Timepoint [2] 0 0
Up to 6 years 4 months
Secondary outcome [3] 0 0
Duration of Response (DoR)
Timepoint [3] 0 0
Up to 6 years 4 months
Secondary outcome [4] 0 0
Maximum Observed Concentration (Cmax)
Timepoint [4] 0 0
Up to 90 days after last dose
Secondary outcome [5] 0 0
Area Under the Concentration-time Curve (AUC)
Timepoint [5] 0 0
Up to 90 days after last dose
Secondary outcome [6] 0 0
Minimum Observed Concentration (Cmin)
Timepoint [6] 0 0
Up to 90 days after last dose
Secondary outcome [7] 0 0
Time to Reach Maximum Concentration (Tmax)
Timepoint [7] 0 0
Up to 90 days after last dose
Secondary outcome [8] 0 0
Trough Plasma Concentration (Ctrough)
Timepoint [8] 0 0
Up to 90 days after last dose
Secondary outcome [9] 0 0
Half Life (t1/2) of AZD0486
Timepoint [9] 0 0
Up to 90 days after last dose
Secondary outcome [10] 0 0
Clearance (CL) of AZD0486
Timepoint [10] 0 0
Up to 90 days after last dose
Secondary outcome [11] 0 0
Number of Participants with Anti-drug Antibody (ADA) for AZD0486
Timepoint [11] 0 0
Up to 90 days after last dose

Eligibility
Key inclusion criteria
Master Inclusion Criteria applicable to all substudies:

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
* Contraception use during treatment and at least 90 days after final dose.
* Confirmed CD19 expression if prior anti-CD19 therapy.

Substudy 1 Specific

* Participants with CLL must require treatment according to the international workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria.
* SLL: at least 1 measurable site per Lugano.
* Absolute lymphocytes <10,000.
* Cohort 1A and 1C: at least 2 prior lines of systemic therapy for CLL/SLL.
* Cohort 1B: at least 1 prior line of therapy and is bruton tyrosine kinase inhibitor (BTKi)-sensitive.

Substudy 2 Specific

* MCL diagnosis per WHO.
* Clinical Stage II, III, or IV by Ann Arbor Classification.
* At least 1 measurable site per Lugano.
* ALC < 10,000.
* Cohort 2A and 2C: Relapse or progressed after 2 or more lines of therapy including BTKi.

Substudy 3 Specific

* Large B-cell lymphoma per WHO 2022.
* R/R B-NHL after at least 1 prior line of therapy.
* International Prognostic Index (IPI) 2-5.
* At least 1 measurable site as per Lugano.
* Left ventricular ejection fraction (LVEF) >50%.
* Contraception at least 90 days after last dose of AZD0486 or 4 months after last dose of vincristine, and 6 months after the last dose of cyclophosphamide, or doxorubicin.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Master Exclusion Criteria applicable to all substudies:

* Central nervous system (CNS) lymphoma.
* Surgery within 14 days of study drug.
* Clinically significant cardiovascular (CV) disease.
* Unresolved Grade >2 AEs from prior anticancer therapy (except alopecia or fatigue).
* Any anticancer therapy within 5 half-lives or 21 days (whichever is shorter) prior to treatment.
* Radiation therapy within 28 days.
* Prior CAR T-cell therapy or autologous-haematopoietic stem cell transplant (HSCT) within 12 weeks or prior T-cell engager (TCE) within 8 weeks.
* Prior Grade > 3 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) event.
* Prior allogeneic HSCT or solid organ transplantation within 24 weeks of starting Cycle 1 Day 1.

Substudy 1 Specific

* CLL transformation to more aggressive lymphoma.
* Cohort 1B: bleeding diathesis, CYP3A inhibitor or inducer, history of ICH or stroke within 24 weeks, GI malabsorption, receiving vitamin K antagonist.

Substudy 3 Specific

* Mediastinal grey-zone lymphoma, Burkitt, Richter's transformation, primary effusion large B-cell lymphoma (LBCL).
* Cumulative dose of anthracycline >150 mg/m2.

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
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 - Heidelberg
Recruitment hospital [2] 0 0
Research Site - Melbourne
Recruitment hospital [3] 0 0
Research Site - Nedlands
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
New Jersey
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Oregon
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Rhode Island
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
China
State/province [10] 0 0
Beijing
Country [11] 0 0
China
State/province [11] 0 0
Guangzhou
Country [12] 0 0
China
State/province [12] 0 0
Jinan
Country [13] 0 0
China
State/province [13] 0 0
Tianjin
Country [14] 0 0
China
State/province [14] 0 0
Zhengzhou
Country [15] 0 0
Czechia
State/province [15] 0 0
Ostrava - Poruba
Country [16] 0 0
Czechia
State/province [16] 0 0
Prague
Country [17] 0 0
Czechia
State/province [17] 0 0
Praha 2 - Nové Mesto
Country [18] 0 0
Denmark
State/province [18] 0 0
Aalborg
Country [19] 0 0
Denmark
State/province [19] 0 0
Aarhus N
Country [20] 0 0
Denmark
State/province [20] 0 0
Copenhagen
Country [21] 0 0
Denmark
State/province [21] 0 0
Odense C
Country [22] 0 0
France
State/province [22] 0 0
Clermont-Ferrand
Country [23] 0 0
France
State/province [23] 0 0
Montpellier
Country [24] 0 0
France
State/province [24] 0 0
Paris
Country [25] 0 0
France
State/province [25] 0 0
Saint-Cloud
Country [26] 0 0
France
State/province [26] 0 0
Villejuif
Country [27] 0 0
Germany
State/province [27] 0 0
Cologne
Country [28] 0 0
Germany
State/province [28] 0 0
Kiel
Country [29] 0 0
Germany
State/province [29] 0 0
München
Country [30] 0 0
Germany
State/province [30] 0 0
Würzburg
Country [31] 0 0
Japan
State/province [31] 0 0
Kotoku
Country [32] 0 0
Japan
State/province [32] 0 0
Matsuyama
Country [33] 0 0
Japan
State/province [33] 0 0
Nagoya
Country [34] 0 0
South Korea
State/province [34] 0 0
Busan
Country [35] 0 0
South Korea
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
Palma de Mallorca
Country [39] 0 0
Spain
State/province [39] 0 0
Santiago de Compostela
Country [40] 0 0
Spain
State/province [40] 0 0
Valencia
Country [41] 0 0
Taiwan
State/province [41] 0 0
Changhua
Country [42] 0 0
Taiwan
State/province [42] 0 0
Kaohsiung City
Country [43] 0 0
Taiwan
State/province [43] 0 0
Tainan City
Country [44] 0 0
Taiwan
State/province [44] 0 0
Taipei
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Derriford
Country [46] 0 0
United Kingdom
State/province [46] 0 0
London
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Oxford

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
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 there quest 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 approved.

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 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 anonymized individual patient-level data via secure research environment Vivli.org. A 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.