Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT03201965 | A Study to Evaluate the Efficacy and Safety of Daratumumab in Combination With Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to CyBorD Alone in Newly Diagnosed Systemic Amyloid Light-chain (AL) Amyloidosis | PHASE3 | COMPLETED | 416 | — | — | Oct 5, 2017 | Nov 19, 2024 | Nov 26, 2025 | 140 | United States, Australia +20 |
| NCT05250973 | A Study of Daratumumab-Based Therapies in Participants With Amyloid Light Chain (AL) Amyloidosis | PHASE2 | ACTIVE NOT_RECRUITING | 151 | — | — | Mar 1, 2022 | Oct 26, 2026 | Jun 5, 2026 | 46 | United States, Canada +8 |
Overall CHR rate was defined as percentage of participants who achieved CHR, according to the International Amyloidosis Consensus Criteria. CHR: normalization of free light chain levels and ratio, negative serum, and urine immunofixation. If involved free light chain (iFLC) is less than (\<) upper limit of normal (ULN) and serum and urine Immunofixation electrophoresis (IFE) are negative, then neither a normal uninvolved free light chain (uFLC) level nor a normal free light chain (FLC) ratio are required for complete response (CR).
Number of participants with cardiac events of any toxicity grade will be reported.
Ctrough is defined as the observed concentration immediately prior to the next study treatment administration.
| Arm | Type | Description |
|---|---|---|
| CyBorD alone (cyclophosphamide/bortezomib/dexamethasone) | ACTIVE_COMPARATOR | Participants will receive dexamethasone (40 milligrams \[mg\] orally or intravenous \[IV\] dose), followed by cyclophosphamide (300 milligram per meter square \[mg/m\^2\] orally or IV dose), then bortezomib (1.3 mg/m\^2 subcutaneous injection) weekly on Days 1, 8, 15, 22 in every 28-day cycle for a maximum of 6 cycles. |
| CyBorD plus Daratumumab | EXPERIMENTAL | Participants will receive dexamethasone (20 mg orally or IV dose as premedication and 20 mg on the day after daratumumab dosing) followed by 1800 mg of daratumumab subcutaneously followed by cyclophosphamide (300 mg/m\^2 orally or IV dose weekly) and bortezomib (1.3 mg/m\^2 subcutaneous injection weekly) on Days 1, 8, 15, 22 in every 28-day cycle for a maximum of 6 cycles. Daratumumab will be administered weekly for the first 8 weeks (2 cycles), then every 2 weeks for 4 cycles (cycles 3-6), and then every 4 weeks until progression of disease or subsequent therapy for a maximum of 2 years. |
| Cohort1 (Arm A): Daratumumab + Immediate Cyclophosphamide, Bortezomib and Dexamethasone (VCd) | EXPERIMENTAL | Participants with newly diagnosed systemic amyloid light chain (AL) amyloidosis with Mayo Cardiac Stage II and IIIa cardiac involvement will receive daratumumab 1800 milligrams (mg) subcutaneously (SC) starting on Day 1 once weekly (q1w) up to Day 22 for cycles 1-2, on Days 1 and 15 for cycles 3-6, and on Day 1 for cycles 7-24 of a 28-day cycle. Participants will also receive VCd (cyclophosphamide 300 milligrams per meter square \[mg/m\^2\] either orally or intravenously \[IV\], bortezomib 1.3 mg/m\^2 SC or IV, dexamethasone 40 mg weekly either orally or IV) weekly starting at Cycle 1 Day 1 up to Day 22 in every 28-day cycle for a maximum of 6 cycles (Cycle 6 Day 22). |
| Cohort1 (Arm B): Daratumumab + Deferred VCd | EXPERIMENTAL | Participants with newly diagnosed systemic AL amyloidosis with Mayo Cardiac Stage II and IIIa cardiac involvement will receive SC daratumumab 1800mg on Day 1 once weekly (q1w) up to Day 22 for cycles 1-2, on Days 1 and 15 for cycles 3-6, and on Day 1 for cycles 7-24 of a 28-day cycle. Participants will also receive VCd (Cyclophosphamide 300 mg/m\^2 either orally or IV, Bortezomib 1.3 mg/m\^2 SC or IV, Dexamethasone 40 mg weekly either orally or IV) starting at Cycle 4 Day 1, weekly (Days 1, 8, 15, 22) in every 28-day cycle for a maximum of 6 cycles (Cycle 9 Day 22). |
| Cohort 2: Daratumumab + VCd | EXPERIMENTAL | Participants with racial and ethnic minorities, including Black or African American participants, with newly diagnosed AL amyloidosis will receive SC injection of daratumumab 1800 mg SC on Day 1 once weekly (q1w) up to Day 22 for cycles 1-2, on Days 1 and 15 for cycles 3-6, and on Day 1 for cycles 7-24 of a 28-day cycle. Participants will also receive VCd (cyclophosphamide 300 milligrams per meter square \[mg/m\^2\] either orally or intravenously \[IV\], bortezomib 1.3 mg/m\^2 SC or IV, dexamethasone 40 mg weekly either orally or IV) weekly starting at Cycle 1 Day 1 up to Day 22 in every 28-day cycle for a maximum of 6 cycles (Cycle 6 Day 22). |
| Name | Type | Description |
|---|---|---|
| Cyclophosphamide | DRUG | Participants will receive 300 mg/m\^2 of cyclophosphamide as an oral or IV dose. |
| Bortezomib | DRUG | Participants will receive 1.3 mg/m\^2 of bortezomib as an subcutaneous (SC) injection. |
| Dexamethasone, 40 mg | DRUG | Participants of CyBorD alone arm will receive 40 mg dexamethasone orally or IV dose. Participants of CyBorD plus daratumumab arm will receive dexamethasone 20 mg orally or IV dose as premedication and 20 mg on the day after daratumumab dosing to make a total of 40 mg. |
| Daratumumab | DRUG | Participants will receive 1800 mg of daratumumab subcutaneously. |
| Dexamethasone | DRUG | Dexamethasone will be administered orally or IV. |
Inclusion Criteria: * Histopathological diagnosis of amyloidosis based on detection by immunohistochemistry and polarizing light microscopy of green bi-refringent material in congo red stained tissue specimens (in an organ other than bone marrow) or characteristic electron microscopy appearance * M...