RECRUITING

A Study of AZD0486 in Subjects With B-Cell Non-Hodgkin Lymphoma

Conditions

B-cell Non Hodgkin Lymphoma Diffuse Large B Cell Lymphoma High-grade B-cell Lymphoma Follicular Lymphoma NHL DLBCL HGBL CD19 FL

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase 1 study will investigate the safety, tolerability, pharmacokinetic, pharmacodynamic, and clinical activity of AZD0486, a CD19 x CD3 T-cell engaging bispecific antibody, in subjects with B-cell non-Hodgkin lymphoma (B-NHL).

Official Title

A Multicenter, Phase 1, Open-label, Dose-escalation and Expansion Study of AZD0486, a Bispecific Antibody Targeting CD19 in Subjects With B-Cell Non-Hodgkin Lymphoma

Quick Facts

Study Start:2021-03-02

Study Completion:2028-04-19

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04594642

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 130 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Biopsy proven B-NHL, including DLBCL, HGBL, or FL. * Relapsed/refractory cohorts: * 1L FL cohorts: Subject has biopsy-proven FL Grade 1-3a per WHO 2016 classification, Stage II-IV, FL International Prognostic Index 2-5 that has not been treated with prior systemic lymphoma-directed therapy and requires initiation of treatment based on GELF criteria. Radiation to localized disease prior to study entry is allowed if \>14 days from first dose. * All Cohorts: * 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	* 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 (\>5,000 circulating lymphoma cells/uL in the peripheral blood). * 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.

Inclusion Criteria

Exclusion Criteria

* Biopsy proven B-NHL, including DLBCL, HGBL, or FL.
* Relapsed/refractory cohorts:
* 1L FL cohorts: Subject has biopsy-proven FL Grade 1-3a per WHO 2016 classification, Stage II-IV, FL International Prognostic Index 2-5 that has not been treated with prior systemic lymphoma-directed therapy and requires initiation of treatment based on GELF criteria. Radiation to localized disease prior to study entry is allowed if \>14 days from first dose.
* All Cohorts:
* 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

* 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 (\>5,000 circulating lymphoma cells/uL in the peripheral blood).
* 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.

Contacts and Locations

Study Contact

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479

information.center@astrazeneca.com

Principal Investigator

David Sermer, MD

STUDY_DIRECTOR

AstraZeneca

Study Locations (Sites)

Research Site

Tampa, Florida, 33612

United States

Research Site

Louisville, Kentucky, 40207

United States

Research Site

New Brunswick, New Jersey, 08901

United States

Research Site

Charlotte, North Carolina, 28204

United States

Research Site

Columbus, Ohio, 43210

United States

Research Site

Portland, Oregon, 97239

United States

Research Site

Pittsburgh, Pennsylvania, 15237

United States

Research Site

Austin, Texas, 78704

United States

Research Site

Houston, Texas, 77030

United States

Research Site

Milwaukee, Wisconsin, 53226

United States

Collaborators and Investigators

Sponsor: AstraZeneca

David Sermer, MD, STUDY_DIRECTOR, AstraZeneca

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-03-02

Study Completion Date2028-04-19

Study Record Updates

Study Start Date2021-03-02

Study Completion Date2028-04-19

Terms related to this study

Keywords Provided by Researchers

NHL
DLBCL
HGBL
CD19
FL

Additional Relevant MeSH Terms

B-cell Non Hodgkin Lymphoma
Diffuse Large B Cell Lymphoma
High-grade B-cell Lymphoma
Follicular Lymphoma