AZD0486 1L Therapy for Elderly or Unfit Participants With LBCL
- Conditions
- Large B-cell Lymphoma
- Interventions
- Drug: R-mini-CHOP
- Registration Number
- NCT07215585
- Lead Sponsor
- AstraZeneca
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 420
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase III Arm A: R-mini-CHOP and AZD0486 AZD0486 2 cycles of R-mini-CHOP followed sequentially by multiple cycles of AZD0486 at RP3D. Phase III Arm A: R-mini-CHOP and AZD0486 R-mini-CHOP 2 cycles of R-mini-CHOP followed sequentially by multiple cycles of AZD0486 at RP3D. Phase III Arm B: R-mini-CHOP R-mini-CHOP 6 cycles of R-mini-CHOP per SoC regimen. Safety Run in: R-mini-CHOP and AZD0486 AZD0486 R-mini-CHOP followed sequentially by AZD0486 at RP2D. Safety Run in: R-mini-CHOP and AZD0486 R-mini-CHOP R-mini-CHOP followed sequentially by AZD0486 at RP2D.
- Primary Outcome Measures
Name Time Method SRI - Safety evaluation of R-mini-CHOP × 2 followed by AZD0486: Number of participants with treatment-related adverse events. Up to 1 year Incidence and severity of AEs, SAEs, AESIs, and events of clinical interest based on NCI CTCAE v5.0/ASTCT, vital signs, laboratory parameters.
SRI - Tolerability evaluation of R-mini-CHOP × 2 followed by AZD0486: Number of participants with treatment-related adverse events. Up to 1 year AEs leading to study treatment discontinuation or dose modification based on NCI CTCAE v5.0/ASTCT, vital signs, laboratory parameters.
SRI - Determination of the recommended Phase III dose (RP3D) Up to 1 year 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
Phase 3 - To demonstrate the superiority of R-mini-CHOP x2 followed by AZD0486 compared to R-mini-CHOP x6 regimen. Up to 7 years Progression-free Surival (PFS), based on Lugano 2014 Response Criteria.
- Secondary Outcome Measures
Name Time Method Phase 3 - Time to First Subsequent Therapy or Death (TFST) Up to 7 Years 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.
Phase 3 - Safety evaluation of R-mini-CHOP × 2 followed by AZD0486: Number of participants with treatment-related adverse events. Up to 7 years Incidence and severity of AEs, SAEs, AESIs, and events of clinical interest based on NCI CTCAE v5.0/ASTCT, vital signs, laboratory parameters.
Phase 3 - Tolerability evaluation of R-mini-CHOP × 2 followed by AZD0486: Number of participants with treatment-related adverse events. Up to 7 years AEs leading to study treatment discontinuation or dose modification based on NCI CTCAE v5.0/ASTCT, vital signs, laboratory parameters.
Safety Run-In and Phase 3 - ORR Up to 7 years 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.
Safety Run-In and Phase 3 - CR Rate Up to 7 years 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.
Safety Run-In and Phase 3 - DoR Up to 7 years 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.
Safety Run-In and Phase 3 - DoCR Up to 7 years 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.
Safety Run-In and Phase 3 - PFS Up to 7 years 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.
Safety Run In and Phase 3 - OS Up to 7 years OS defined as the time from date of the first dose until death due to any cause.
Phase 3 - Time from randomisation to second progression or death (PFS2) Up to 7 years 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.
Safety Run-In and Phase 3 - Pharmacokinetics of AZD0486: serum concentration of study drug Up to 7 years Maximum observed serum concentration of AZD0486.
Safety Run-In and Phase 3 - Pharmacokinetics of AZD0486: Maximum plasma concentration of the study drug (Cmax). Up to 7 years Maximum observed plasma concentration of AZD0486.
Safety Run-In and Phase 3 - Pharmacokinetics of AZD0486: Concentration of study drug reached before next dose (Ctrough). Up to 7 years Observed plasma concentration of AZD0486 right before next dose of AZD0486.
Safety Run-In and Phase 3 - To determine the immunogenicity of AZD0486 Up to 7 years Summary of pre-existing and treatment induced ADAs for AZD0486 (positive or negative, titres) and the impact on PK, efficacy or safety.
Phase 3 - Safety evaluation of R-mini-CHOP × 2 followed by AZD0486 versus R-mini-CHOP × 6 Up to 7 years Evaluation of key participant-reported side effects (pain, fatigue) and overall treatment tolerability, lymphoma-specific concerns, and HRQoL.
Phase 3 - Efficacy evaluation of R-mini-CHOP × 2 followed by AZD0486 versus R-mini-CHOP × 6 Up to 7 years Evaluation of key participant-reported side effects (pain, fatigue) and overall treatment tolerability, lymphoma-specific concerns, and HRQoL.
Trial Locations
- Locations (1)
Research Site
🇰🇷Seoul, South Korea
Research Site🇰🇷Seoul, South Korea