Across 237 unique European leukemia Phase II and Phase III trials, safety/tolerability was the most frequently measured endpoint family, appearing in 175 trials (73.8%), followed by overall survival in 170 (71.7%), response/remission in 155 (65.4%), and measurable/minimal residual disease or molecular response in 131 (55.3%). Leukemia endpoint strategy is disease-specific: CLL/SLL trials emphasized response and progression-free survival, ALL trials emphasized safety, survival, relapse and MRD, while AML trials balanced safety, overall survival, remission and relapse endpoints.
The four most common endpoint families were safety/tolerability in 175 of 237 trials (73.8%), overall survival (OS) in 170 (71.7%), response/remission in 155 (65.4%), and measurable/minimal residual disease (MRD) or molecular response in 131 (55.3%).
European leukemia trials do not rely on a single efficacy endpoint. Most protocols combine clinical outcome endpoints such as OS, remission/response and relapse-free measures with hematologic depth-of-response endpoints such as MRD.
As primary endpoints, response/remission appeared in 81 of 237 trials (34.2%), safety/tolerability in 76 (32.1%), and MRD/molecular response in 61 (25.7%). As secondary endpoints, OS appeared in 159 trials (67.1%), safety/tolerability in 147 (62.0%), and response/remission in 128 (54.0%). Exploratory endpoint language was concentrated in biomarker/correlative analyses, appearing in 18 trials (7.6%).
| Endpoint family | Primary | Secondary | Exploratory |
|---|---|---|---|
| Response / remission | 81 (34.2%) | 128 (54.0%) | 6 (2.5%) |
| Safety / tolerability | 76 (32.1%) | 147 (62.0%) | 6 (2.5%) |
| MRD / molecular response | 61 (25.7%) | 115 (48.5%) | 8 (3.4%) |
| Overall survival | 21 (8.9%) | 159 (67.1%) | 6 (2.5%) |
| Biomarker / correlative | 23 (9.7%) | 63 (26.6%) | 18 (7.6%) |
Leukemia trial sponsors most often use remission, MRD and safety as decision-driving primary endpoints, while OS is more commonly retained as a secondary confirmatory or long-term outcome.
The largest disease families were AML in 92 trials, CLL/SLL/Richter transformation in 64, and ALL in 56. AML trials most often measured safety and OS (65/92 each; 70.7%), CLL/SLL trials most often measured response/remission (49/64; 76.6%) and PFS/OS (47/64 each; 73.4%), while ALL trials most often measured safety (49/56; 87.5%), OS (43/56; 76.8%), relapse/DFS/RFS (40/56; 71.4%) and MRD (38/56; 67.9%).
| Disease family | Trials | Most frequent endpoint families |
|---|---|---|
| AML | 92 | Safety 65 (70.7%); OS 65 (70.7%); response/remission 61 (66.3%) |
| CLL/SLL/Richter | 64 | Response/remission 49 (76.6%); OS 47 (73.4%); PFS 47 (73.4%) |
| ALL | 56 | Safety 49 (87.5%); OS 43 (76.8%); relapse/DFS/RFS 40 (71.4%) |
| Other / mixed leukemia | 21 | OS 14 (66.7%); safety 13 (61.9%); response/remission 13 (61.9%) |
| CML | 18 | MRD/molecular response 13 (72.2%); safety 13 (72.2%); OS 11 (61.1%) |
CLL/SLL studies look more lymphoma-like, with high PFS and response use, while ALL and AML studies remain anchored in remission depth, relapse, MRD and OS. CML is smaller but strongly molecular-response oriented.
The largest sub-disease groups were CLL/SLL with 64 trials, pediatric ALL with 31, B-cell precursor ALL with 19, CML with 17, and Ph+/BCR-ABL+ ALL with 12. Relapsed B-cell/ALL and relapsed/refractory AML were smaller but still analyzable at 10 and 8 trials, respectively.
| Sub-disease group | Trials | Leading endpoint signal |
|---|---|---|
| CLL/SLL | 64 | Response/remission 49 (76.6%); OS and PFS 47 each (73.4%) |
| Pediatric ALL | 31 | Safety 29 (93.5%); OS 24 (77.4%); relapse/DFS/RFS 23 (74.2%) |
| B-cell precursor ALL | 19 | Safety 17 (89.5%); OS and response/remission 13 each (68.4%) |
| CML | 17 | MRD/molecular response and safety 12 each (70.6%) |
| Ph+/BCR-ABL+ ALL | 12 | Relapse/DFS/RFS and OS 10 each (83.3%) |
| Relapsed B-cell/ALL | 10 | Safety 10 (100.0%); MRD and OS 9 each (90.0%) |
| Relapsed/refractory AML | 8 | Safety 5 (62.5%); response/remission 4 (50.0%) |
Endpoint selection becomes more specialized at sub-disease level: CLL/SLL concentrates on response and PFS, pediatric and relapsed ALL emphasize safety and relapse/MRD, while CML remains molecular-response driven.
Among 152 Phase II-containing trials, safety/tolerability appeared in 126 (82.9%), OS in 110 (72.4%), and response/remission in 103 (67.8%). Among 76 Phase III-containing trials, OS appeared in 53 (69.7%), response/remission in 45 (59.2%), and safety/tolerabil