Large B-cell Lymphoma
Conditions
Keywords
Large B-cell Lymphoma, LBCL, AZD0486, CD3, CD19, TCE, B-cell malignancies, Soundtrack-D2
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.
Interventions
DRUGAZD0486
Bispecific monoclonal IgG4 antibody
DRUGR-mini-CHOP
Intravenous administration: Rituximab 375 mg/m2, Cyclophosphamide 400 mg/m2, Doxorubicin 25 mg/m2, Vincristine 1 mg, and Oral administration: Prednisone 40 mg/m2
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study consists of 2 sequential parts: a safety run-in (SRI) followed by the phase III.
Eligibility
Sex/Gender
ALL
Age
65 Years to 130 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 - 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. |
Countries
Australia, Belgium, Brazil, Canada, China, Hong Kong, Japan, Poland, South Korea, Turkey (Türkiye), United Kingdom
Contacts
CONTACTAstraZeneca Clinical Study Information Center
PRINCIPAL_INVESTIGATORMichael Dickinson,, MBBS BS DMSc
Peter MacCallum Cancer Center
Outcome results
None listed