A Study of AZD0486 Plus Rituximab in Previously Untreated Follicular Lymphoma Patients
- Conditions
- Untreated Follicular Lymphoma
- Interventions
- Registration Number
- NCT06549595
- Lead Sponsor
- AstraZeneca
- Brief Summary
This is a global, randomised, Phase III, multicentre, open-label study evaluating the efficacy, safety and the degree of added benefit of the AZD0486 plus rituximab combination compared to Investigator's choice of 3 standard immunochemotherapy regimen, conducted in participants with untreated FL.
- Detailed Description
The study consists of 2 sequential parts.
1. Safety Run-in - this part will compare dose levels of AZD0486 in combination with rituximab in order to establish the RP3D.
2. Phase III - The Phase III part will assess the superiority of AZD0486 at RP3D in combination with rituximab, compared to Investigator's choice between 3 standard chemoimmunotherapy regimens. Phase 3 consists of 3 arms
1. Arm A: treatment with AZD0486 plus rituximab Schedule A
2. Arm B: treatment with AZD0486 plus rituximab Schedule B
3. Arm C (Comparator arm): one of the following standard regimens per Investigator's choice: R-CVP + rituximab maintenance, R-CHOP + rituximab maintenance and B-R
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1015
- Participant must be at least 18 years of age, inclusive, at the time of signing the ICF.
- Histologically confirmed diagnosis of FL Grades 1-3A per WHO 2016 classification
- ECOG performance status of 0 to 2
- No prior systemic lymphoma-directed therapy
- Need for systemic treatment meeting at least 1 GELF criteria
- FDG-avid and measurable disease
- Adequate liver, hematological, renal and cardiac function.
The above is a summary, other inclusion criteria details may apply
- Follicular lymphoma Grade 3B (WHO 2016 classification) or suspicion for histologic transformation to high-grade/aggressive lymphoma
- Contra-indication to BR, RCVP, and R-CHOP
- Participants with or history of CNS lymphoma
- Presence of >5000 circulating lymphoma cells
- Active or uncontrolled infection requiring systemic therapy and which places participant at unacceptable risk if he/she were to participate in the study
The above is a summary, other exclusion criteria details may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Rituximab, AZD0486 - A AZD0486 AZD0486 regimen A plus rituximab Rituximab, AZD0486 - B AZD0486 AZD0486 regimen B plus rituximab Chemoimmunotherapy BR Investigator's choice between 3 standard immunochemotherapy regimen (R-CHOP or R-CVP followed by rituximab maintenance, or B-R) Chemoimmunotherapy R-CHOP Investigator's choice between 3 standard immunochemotherapy regimen (R-CHOP or R-CVP followed by rituximab maintenance, or B-R) Chemoimmunotherapy R-CVP Investigator's choice between 3 standard immunochemotherapy regimen (R-CHOP or R-CVP followed by rituximab maintenance, or B-R)
- Primary Outcome Measures
Name Time Method SRI Primary: Incidence, nature and severity of AEs and SAEs. Incidence and nature of study drug discontinuations, dose reductions, and dose delays due to AEs Up to 10 years Frequency, severity, and relationship to study drug of AEs and SAEs; dose modifications; changes in physical examination and safety procedures.
SRI Primary: 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 Primary: To demonstrate the superiority of AZD0486 plus rituximab compared to Investigator's choice of SoC chemoimmunotherapy Up to 10 years PFS, based on Lugano 2014 Response Criteria, as assessed by BICR.
- Secondary Outcome Measures
Name Time Method Safety Run In and Phase 3: PFS Up to 10 years PFS is defined as time until disease progression based on Lugano 2014 Response Criteria
Safety Run in and Phase 3: ORR Up to 10 years ORR defined as the proportion of participants achieving either a PR or CR at any time based on Lugano 2014 Response Criteria
Safety Run In and Phase 3: CR Rate Up to 10 years CR rate is defined as the proportion of participants achieving a CR at any time as based on Lugano 2014 Response Criteria
Safety Run In and Phase 3: CR at EoI Up to 10 years Proportion of participants achieving CR at End of Induction based on Lugano 2014 Response Criteria
Safety Run In and Phase 3: DoR up to 10 years DoR will be defined as the time from the time of first response until progression based on Lugano 2014 criteria
Phase 3: CR rate at 30 months Up to 10 Years Proportion of participants in CR rate at 30 months (CR30) based on Lugano 2014 Response Criteria
Safety Run In and Phase 3: OS Up to 10 years OS is defined as time until the date of death
Trial Locations
- Locations (1)
Research Site
🇬🇧Norwich, United Kingdom