AZD0486 1L Therapy for Elderly or Unfit Participants With LBCL

Phase 3RecruitingNCT07215585

AstraZeneca420 enrolled

Overview

The purpose of this study is to measure the efficacy and safety of R-mini-CHOP × 2 followed by AZD0486 compared with R-mini-CHOP × 6 in elderly or unfit participants newly diagnosed with LBCL.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

420

Conditions

Large B-cell Lymphoma

Interventions

AZD0486DRUG

Bispecific monoclonal IgG4 antibody

R-mini-CHOPDRUG

Intravenous administration: Rituximab 375 mg/m2, Cyclophosphamide 400 mg/m2, Doxorubicin 25 mg/m2, Vincristine 1 mg, and Oral administration: Prednisone 40 mg/m2

Eligibility

Sex: ALLMin age: 65 YearsMax age: 130 Years

Medical Language ↔ Plain English

Inclusion criteria: * Participants are either 80 years of age or older, OR 65 to 79 years of age or older and classified as unfit per sGA, and otherwise not considered candidates for full-dose R-CHOP per investigator assessment; * Histologically confirmed diagnosis of previously untreated LBCL as per WHO-HEM5 (excluding plasmablastic lymphoma) and follicular large cell lymphoma; * FDG-avid and measurable disease as per Lugano and Ann Arbor staging; * Stage I bulky (7.5 cm and greater) to Stage IV; * ECOG performance status 0 to 2; * Adequate bone marrow, liver, renal and cardiac function. The above is a summary, other inclusion criteria details may apply. * As judged by the investigator, any evidence of diseases which make it undesirable for the participant to participate in the study, or that would jeopardise compliance with the protocol * Diagnosis of post-transplant lymphoproliferative disease, plasmablastic lymphoma, Richter's transformation, prior history of or concurrent indolent lymphoma (including de novo transformed or composite lymphoma). * History of CNS involvement by their B-NHL or history of clinically relevant CNS medical condition * Known history of hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). * Active or uncontrolled infection * Major cardiac abnormalities * Prior anti-lymphoma therapy except for corticosteroids for symptom control * Requires chronic immunosuppressive therapy for active autoimmune/inflammatory condition, with some exceptions The above is a summary, other exclusion criteria details may apply.

Locations (68)

Outcomes

Primary Outcomes

SRI - Safety evaluation of R-mini-CHOP × 2 followed by AZD0486: Number of participants with treatment-related adverse events.

Incidence and severity of AEs, SAEs, AESIs, and events of clinical interest based on NCI CTCAE v5.0/ASTCT, vital signs, laboratory parameters.

Time frame: Up to 1 year

SRI - Tolerability evaluation of R-mini-CHOP × 2 followed by AZD0486: Number of participants with treatment-related adverse events.

AEs leading to study treatment discontinuation or dose modification based on NCI CTCAE v5.0/ASTCT, vital signs, laboratory parameters.

Time frame: Up to 1 year

SRI - Determination of the recommended Phase III dose (RP3D)

The RP3D will be the dose of AZD0486 selected for the Phase 3 part based on safety data compiled during the Safety Run-In part

Time frame: Up to 1 year

Phase 3 - To demonstrate the superiority of R-mini-CHOP x2 followed by AZD0486 compared to R-mini-CHOP x6 regimen.

Progression-free Surival (PFS), based on Lugano 2014 Response Criteria.

Time frame: Up to 7 years

Secondary Outcomes

Safety Run-In and Phase 3 - ORR

ORR defined as the proportion of participants achieving either a PR or CR at timepoints defined in the study protocol, based on Lugano 2014 Response Criteria as determined by Investigator assessment.

Time frame: Up to 7 years

Safety Run-In and Phase 3 - CR Rate

CR rate is defined as the proportion of participants achieving a CR at timepoints defined in the study protocol, based on Lugano 2014 Response Criteria as determined by Investigator assessment.

Time frame: Up to 7 years

Central Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479 information.center@astrazeneca.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Research Site

Clayton, Australia

NOT_YET_RECRUITING

Research Site

Macquarie University, Australia

WITHDRAWN

Research Site

Melbourne, Australia

RECRUITING

Research Site

Nedlands, Australia

NOT_YET_RECRUITING

Research Site

Waratah, Australia

NOT_YET_RECRUITING

Research Site

Antwerp, Belgium

WITHDRAWN

Research Site

Brussels, Belgium

NOT_YET_RECRUITING

Research Site

Ghent, Belgium

RECRUITING

Research Site

Leuven, Belgium

RECRUITING

Research Site

Roeselare, Belgium

SUSPENDED

...and 58 more locations

Safety Run-In and Phase 3 - DoR

DoR is defined as the time from the date of first documented response until the date of documented progression based on Lugano 2014 criteria as determined by Investigator assessment or death due to any cause.

Time frame: Up to 7 years

Safety Run-In and Phase 3 - DoCR

DoCR is defined as the time from the date of first documented CR until the date of documented progression or death due to any cause, as assessed by the Investigator.

Time frame: Up to 7 years

Safety Run-In and Phase 3 - PFS

PFS is defined as the time from date of the first dose to date of documented objective disease progression as per Lugano 2014 or death (by any cause in the absence of progression), as determined by Investigator assessment.

Time frame: Up to 7 years

Safety Run In and Phase 3 - OS

OS defined as the time from date of the first dose until death due to any cause.

Time frame: Up to 7 years

Phase 3 - Time from randomisation to second progression or death (PFS2)

PFS2 is defined as the time from randomisation to the earliest of the progression event (following the initial investigator-assessed progression), after first subsequent therapy, or death.

Time frame: Up to 7 years

Phase 3 - Time to First Subsequent Therapy or Death (TFST)

TFST is defined as time from randomisation until the start date of first subsequent anti-lymphoma therapy after discontinuation of randomised treatment, or death due to any cause.

Time frame: Up to 7 Years

Phase 3 - Safety evaluation of R-mini-CHOP × 2 followed by AZD0486: Number of participants with treatment-related adverse events.

Incidence and severity of AEs, SAEs, AESIs, and events of clinical interest based on NCI CTCAE v5.0/ASTCT, vital signs, laboratory parameters.

Time frame: Up to 7 years

Phase 3 - Tolerability evaluation of R-mini-CHOP × 2 followed by AZD0486: Number of participants with treatment-related adverse events.

AEs leading to study treatment discontinuation or dose modification based on NCI CTCAE v5.0/ASTCT, vital signs, laboratory parameters.

Time frame: Up to 7 years

Safety Run-In and Phase 3 - Pharmacokinetics of AZD0486: serum concentration of study drug

Maximum observed serum concentration of AZD0486.

Time frame: Up to 7 years

Safety Run-In and Phase 3 - Pharmacokinetics of AZD0486: Maximum plasma concentration of the study drug (Cmax).

Maximum observed plasma concentration of AZD0486.

Time frame: Up to 7 years

Safety Run-In and Phase 3 - Pharmacokinetics of AZD0486: Concentration of study drug reached before next dose (Ctrough).

Observed plasma concentration of AZD0486 right before next dose of AZD0486.

Time frame: Up to 7 years

Safety Run-In and Phase 3 - To determine the immunogenicity of AZD0486

Summary of pre-existing and treatment induced ADAs for AZD0486 (positive or negative, titres) and the impact on PK, efficacy or safety.

Time frame: Up to 7 years

Phase 3 - Safety evaluation of R-mini-CHOP × 2 followed by AZD0486 versus R-mini-CHOP × 6

Evaluation of key participant-reported side effects (pain, fatigue) and overall treatment tolerability, lymphoma-specific concerns, and HRQoL.

Time frame: Up to 7 years

Phase 3 - Efficacy evaluation of R-mini-CHOP × 2 followed by AZD0486 versus R-mini-CHOP × 6

Evaluation of key participant-reported side effects (pain, fatigue) and overall treatment tolerability, lymphoma-specific concerns, and HRQoL.

Time frame: Up to 7 years