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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04594642




Registration number
NCT04594642
Ethics application status
Date submitted
13/10/2020
Date registered
20/10/2020

Titles & IDs
Public title
A Study of AZD0486 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Scientific title
A Multicenter, Phase 1, Open-label, Dose-escalation and Expansion Study of AZD0486, a Bispecific Antibody Targeting CD19 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Secondary ID [1] 0 0
D7400C00006
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-cell Non Hodgkin Lymphoma 0 0
Diffuse Large B Cell Lymphoma 0 0
High-grade B-cell Lymphoma 0 0
Follicular Lymphoma 0 0
Condition category
Condition code
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 IV

Experimental: AZD0486 Monotherapy Dose Escalation in Subjects with RR B-NHL - AZD0486 monotherapy will be administered intravenously on day 1 and 15 of 28 day cycles for a maximum of 2 years or until discontinuation criteria are met. Depending on cohort, subjects may receive priming or step-up dosing during cycle 1 before reaching the target dose. While on study, subjects will be monitored for safety and efficacy with periodic disease assessment with PET/CT. If subject achieves two consecutive CRs after completing C6, then they may be eligible for monthly dosing


Treatment: Drugs: AZD0486 IV
AZD0486 is a bispecific antibody targeting CD19 on tumor cells and CD3 on T-cells leading to T cell-mediated cytotoxicity of malignant B cells
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of subjects with Dose-limiting toxicities (DLT)
Timepoint [1] 0 0
28 days
Primary outcome [2] 0 0
Incidence of subjects with adverse events (AEs) and/or serious adverse events (SAEs)
Timepoint [2] 0 0
From screening until 90 Days after end of treatment
Primary outcome [3] 0 0
Maximum Observed Serum Concentration of AZD0486 (Cmax)
Timepoint [3] 0 0
4 Weeks
Primary outcome [4] 0 0
Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast)
Timepoint [4] 0 0
4 Weeks
Primary outcome [5] 0 0
Apparent terminal half-life (t1/2) of AZD0486
Timepoint [5] 0 0
From screening until 90 Days after end of treatment
Secondary outcome [1] 0 0
Anti-Lymphoma Activity by Objective Response Rate (ORR)
Timepoint [1] 0 0
48 months
Secondary outcome [2] 0 0
Anti-Lymphoma Activity by Progression-Free Survival (PFS)
Timepoint [2] 0 0
48 months
Secondary outcome [3] 0 0
Anti-Lymphoma Activity by Duration of Objective Response (DOR)
Timepoint [3] 0 0
48 months
Secondary outcome [4] 0 0
Anti-Lymphoma Activity by Clinical Benefit Rate
Timepoint [4] 0 0
48 months

Eligibility
Key inclusion criteria
* Biopsy proven B-NHL, including DLBCL, HGBL, or FL.

-. In order to be eligible for this study subjects must not be candidates for treatment regimens known to provide clinical benefit in B-NHL. CAR T-naive subjects are allowed if they have declined, are considered ineligible for, or do not have timely access to CAR T cell therapies.
* Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of = 2.
* Subject must have adequate liver, bone marrow and kidney function (eGFR = 50 mL/min).
* Subject must have locally confirmed CD19 positivity (must be documented after time of progression from last CD19-targeted therapy, if received)
* Subject must have at least 1 measurable disease site
* Subject must have ANC >/= 1000/mm3, platelets >/= 50,000 mm3, hemoglobin >/= 8.0 g/dL. Transfusion and/or growth factor are allowed but counts must be stable for at least 72 hours afterwards prior to screening
* Subject must have a total bilirubin <1.5x ULN, AST/ALT < 3xULN
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Subject has been diagnosed with or treated for another malignancy whose natural history or treatment may interfere with the safety or efficacy assessment of the investigational regimen.
* Subject has active central nervous system (CNS) involvement by their B-NHL. Subjects may be eligible with a distant history of CNS involvement that has been adequately treated with no evidence of recurrence within last 6 months from screening.
* Subject has a history of leukemic presentation of their B-NHL.
* Subject has history or presence of clinically significant CNS pathology
* Subject has CNS involvement from active or history of autoimmune disease.
* Subject received CD19 CAR T therapy within 3 months prior to first dose.
* Subject experienced Grade = 3 cytokine release syndrome (CRS) following prior T-cell engager (TCE) or CAR T-cell therapy.
* Subject experienced Grade = 2 neurotoxicity/immune effector cell-associated neurotoxicity syndrome (ICANS) following prior TCE or CAR T-cell therapy.
* Subject has received a peripheral autologous stem cell transplant (SCT) within 12 weeks, or an allogeneic SCT within 1 year of the first dose of study drug treatment or has received an SCT and requires ongoing immunosuppressive therapy.
* Subjects with human immunodeficiency virus (HIV) infection, or subjects with chronic or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Subjects with chronic HBV may be enrolled if the HBV viral load is undetectable on suppressive therapy, or if the subject has a documented cure. Subjects with HCV who have a documented cure may be enrolled.
* Subject has a history of major cardiac abnormalities.
* If female, subject must not be pregnant or breastfeeding.

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
2/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/01/2027
Actual
Sample size
Target
231
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Bedford Park
Recruitment hospital [2] 0 0
Research Site - Heidelberg
Recruitment hospital [3] 0 0
Research Site - Hobart
Recruitment hospital [4] 0 0
Research Site - Melbourne
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
7000 - Hobart
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Kentucky
Country [3] 0 0
United States of America
State/province [3] 0 0
New Jersey
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
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Wisconsin
Country [10] 0 0
Japan
State/province [10] 0 0
Chuo-ku
Country [11] 0 0
Japan
State/province [11] 0 0
Koto-ku
Country [12] 0 0
Japan
State/province [12] 0 0
Nagoya-shi
Country [13] 0 0
Japan
State/province [13] 0 0
Yamagata-shi
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Seoul
Country [15] 0 0
Taiwan
State/province [15] 0 0
Kaohsiung City
Country [16] 0 0
Taiwan
State/province [16] 0 0
Kweishan
Country [17] 0 0
Taiwan
State/province [17] 0 0
Tainan
Country [18] 0 0
Taiwan
State/province [18] 0 0
Taipei

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
David Sermer, MD
Address 0 0
AstraZeneca
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 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
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.

Access Criteria:
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://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/NCT04594642