Across 392 European CTIS-authorized haematology Phase II & III trials from 2024–2026, safety/tolerability was the most frequently measured endpoint family, appearing in 287 trials (73.2%). Primary endpoints were split between safety/tolerability in 107 trials (27.3%), response/remission in 104 trials (26.5%), and survival/time-to-event in 96 trials (24.5%), while secondary endpoints were led by safety in 231 trials (58.9%) and survival in 222 trials (56.6%). Disease biology shaped endpoint choice: lymphoma, leukemia and myeloma relied heavily on survival, response and minimal residual disease (MRD), while hemoglobinopathy, MDS/MPN and bleeding/thrombosis trials used more laboratory, bleeding, vaso-occlusive crisis and safety outcomes.
Measured at trial level across primary, secondary and other endpoint fields, safety/tolerability appeared in 287/392 trials (73.2%), followed by survival/time-to-event endpoints in 241/392 (61.5%) and response/remission endpoints in 204/392 (52.0%). Patient-reported outcomes (PROs), quality of life (QoL), MRD/molecular/biomarker endpoints and laboratory endpoints each appeared in more than one-third of the dataset.
For EU CTIS submissions in haematology, endpoint planning is anchored in safety plus standard efficacy outcomes. Sponsors should expect the largest endpoint-definition workload around adverse events, survival definitions, response/remission criteria, MRD/biomarker handling and PRO/QoL instruments.
Primary endpoints were led by safety/tolerability in 107/392 trials (27.3%), response/remission in 104/392 (26.5%) and survival/time-to-event in 96/392 (24.5%). Secondary endpoints carried broader evidence generation: safety appeared in 231/392 trials (58.9%), survival in 222/392 (56.6%), response/remission in 175/392 (44.6%) and PRO/QoL/function in 164/392 (41.8%). Exploratory/other endpoint fields were uncommon, appearing in 15/392 trials (3.8%), with MRD/molecular/biomarker endpoints the leading exploratory family in 10/392 trials (2.6%).
| Endpoint family | Primary | Secondary | Exploratory / other |
|---|---|---|---|
| Safety / tolerability | 107 (27.3%) | 231 (58.9%) | 5 (1.3%) |
| Response / remission | 104 (26.5%) | 175 (44.6%) | 5 (1.3%) |
| Survival / time-to-event | 96 (24.5%) | 222 (56.6%) | 7 (1.8%) |
| Hematologic / lab markers | 69 (17.6%) | 120 (30.6%) | 0 (0.0%) |
| MRD / molecular / biomarker | 64 (16.3%) | 139 (35.5%) | 10 (2.6%) |
| PRO / QoL / function | 11 (2.8%) | 164 (41.8%) | 4 (1.0%) |
| PK / PD / exposure | 33 (8.4%) | 118 (30.1%) | 2 (0.5%) |
The primary endpoint layer is not dominated by a single measure; it balances safety, response and survival. The secondary layer is much broader and is where CTIS submissions most often need detailed schedules for AE capture, time-to-event definitions, response criteria, QoL instruments, PK/PD sampling and MRD/biomarker analyses.
Phase II trials represented 228/392 trials (58.2%) and Phase III trials represented 164/392 (41.8%). In Phase II, response/remission appeared in 149/228 trials (65.4%) and was the leading primary endpoint family in 84/228 trials (36.8%). In Phase III, survival/time-to-event was the leading primary endpoint family in 53/164 trials (32.3%), while PRO/QoL/function endpoints appeared in 81/164 trials (49.4%) and hematologic/lab markers in 72/164 trials (43.9%).
Phase II CTIS submissions are more response- and biomarker-heavy, consistent with signal-seeking haematology development. Phase III submissions shift toward survival, PRO/QoL, hematologic/lab and bleeding/VOC outcomes, reflecting confirmatory clinical benefit and patient-impact evidence.
The largest disease groups were leukemia with 94/392 trials (24.0%), lymphoma/lymphoid malignancies with 90/392 (23.0%), multiple myeloma/plasma-cell disorders with 55/392 (14.0%), hemoglobinopathy/anemia/hemolysis with 50/392 (12.8%), bleeding/platelet/thrombosis disorders with 38/392 (9.7%) and MDS/MPN with 32/392 (8.2%). Survival/time-to-event reached 81/90 lymphoma trials (90.0%), while hematologic/lab markers reached 42/50 hemoglobinopathy/anemia/hemolysis trials (84.0%) and safety reached 28/32 MDS/MPN trials (87.5%).
| Disease group | Trials | Most frequent endpoint families |
|---|---|---|
| Leukemia | 94 | Survival 75 (79.8%); safety 66 (70.2%); response 60 (63.8%); MRD/biomarker 53 (56.4%) |
| Lymphoma / lymphoid malignancies | 90 | Survival 81 (90.0%); response 78 (86.7%); safety 74 (82.2%); PRO/QoL 42 (46.7%) |
| Multiple myeloma / plasma-cell disorders | 55 | Survival 42 (76.4%); safety 40 (72.7%); response 37 (67.3%); MRD/biomarker 35 (63.6%) |
| Hemoglobinopathy / anemia / hemolysis | 50 | Hematologic/lab 42 (84.0%); safety 32 (64.0%); PK/PD 27 (54.0%); PRO/QoL 23 (46.0%) |
| Bleeding, platelet & thrombosis disorders | 38 | Safety 29 (76.3%); bleeding/VOC/thrombosis 29 (76.3%); hematologic/lab 22 (57.9%); PK/PD 21 (55.3%) |
| MDS / MPN | 32 | Safety 28 (87.5%); hematologic/lab 26 (81.2%); PRO/QoL 16 (50.0%); survival 15 (46.9%) |
Haematology endpoint strategy cannot be generalized from oncology alone. Lymphoma, leukemia and myeloma CTIS packages need mature survival, response and MRD language, while non-malignant haematology submissions require stronger laboratory, bleeding/VOC, transfusion, factor activity and patient-function endpoint planning.
Sub-disease counts were sufficient for at least 10-trial comparisons in multiple myeloma, AML, thrombosis/VTE, ALL, DLBCL, sickle cell disease, CLL/SLL, MDS, other lymphoma and mantle cell lymphoma. ALL had the highest survival/time-to-event concentration at 29/31 trials (93.5%), DLBCL paired survival and response in 22/25 trials (88.0% each), and sickle cell disease was led by hematologic/lab endpoints in 18/22 trials (81.8%).
| Sub-disease | Trials | Endpoint pattern |
|---|---|---|
| Multiple myeloma | 52 | Survival 39 (75.0%); safety 37 (71.2%); response 36 (69.2%); MRD 33 (63.5%) |
| Acute myeloid leukemia | 45 | Survival 39 (86.7%); safety 32 (71.1%); response 32 (71.1%); MRD 25 (55.6%) |
| Thrombosis / VTE | 32 | Safety 27 (84.4%); hematologic/lab 24 (75.0%); bleeding/thrombosis 19 (59.4%) |
| Acute lymphoblastic leukemia | 31 | Survival 29 (93.5%); response 26 (83.9%); safety 25 (80.6%); transplant/cellular therapy 22 (71.0%) |
| Diffuse large B-cell lymphoma | 25 | Survival 22 (88.0%); response 22 (88.0%); safety 19 (76.0%) |
| Sickle cell disease | 22 | Hematologic/lab 18 (81.8%); safety 14 (63.6%); bleeding/VOC 13 (59.1%); PRO/QoL 11 (50.0%) |
| CLL / SLL | 19 | Survival 16 (84.2%); response 15 (78.9%); safety 14 (73.7%); MRD 12 (63.2%) |
| Myelodysplastic syndrome | 16 | Safety 13 (81.2%); hematologic/lab 13 (81.2%); survival 9 (56.2%); PRO/QoL 7 (43.8%) |
Sub-disease granularity matters for protocol and CTIS design. DLBCL, AML, ALL, CLL/SLL and myeloma require disease-specific response, MRD and survival criteria, while sickle cell and thrombosis/VTE require endpoint packages centered on laboratory thresholds, crisis/event adjudication, bleeding definitions and patient-function measures.
Modality comparisons were strongest for small molecules, monoclonal antibodies, peptide/protein/enzyme products, bispecific antibodies and cell therapies. Small molecules appeared in 258 trial modality memberships, monoclonal antibodies in 127, peptide/protein/enzyme products in 61, bispecific antibodies in 40 and cell therapies in 38. Bispecific antibodies had the highest survival/time-to-event concentration among these groups at 33/40 trials (82.5%), while small molecules had nearly equal safety and survival frequencies at 190/258 (73.6%) and 189/258 (73.3%).
| Modality group | Trial memberships | Most frequent endpoint families |
|---|---|---|
| Small molecule | 258 | Safety 190 (73.6%); survival 189 (73.3%); response 163 (63.2%); MRD/biomarker 125 (48.4%) |
| Monoclonal antibody | 127 | Safety 99 (78.0%); survival 91 (71.7%); response 85 (66.9%); PRO/QoL 60 (47.2%) |
| Peptide / protein / enzyme | 61 | Safety 37 (60.7%); hematologic/lab 37 (60.7%); survival 32 (52.5%); PRO/QoL 21 (34.4%) |
| Bispecific antibody | 40 | Survival 33 (82.5%); safety 30 (75.0%); response 29 (72.5%); MRD/biomarker 24 (60.0%) |
| Cell therapy | 38 | Safety 29 (76.3%); survival 26 (68.4%); response 22 (57.9%); MRD/biomarker 15 (39.5%) |
For CTIS submissions, modality affects endpoint evidence burden. Bispecific and cell therapy programs require oncology-style survival, response, MRD and safety architecture, while peptide/protein/enzyme products more often need laboratory and functional endpoint packages alongside safety.
The same CTIS endpoint dataset also answers operational questions around endpoint burden, exploratory endpoint rarity, pediatric endpoint differences and orphan-trial endpoint mix. These adjacent findings are useful for EU protocol writing, endpoint schedule design, statistical planning and submission review preparation.
For EU submission teams, the main planning risk is not only selecting the primary endpoint. Most endpoint work sits in secondary schedules, pediatric/non-malignant haematology trials require more lab and event-specific outcomes, and exploratory biomarker language appears selectively rather than universally.
Because these 392 trials are CTIS-authorized European studies with endpoint data, the endpoint patterns indicate what sponsors most often need to define clearly before EU submission. Across the full dataset, CTIS packages most often needed safety/tolerability definitions in 287/392 trials (73.2%), survival/time-to-event definitions in 241/392 (61.5%), response/remission criteria in 204/392 (52.0%), PRO/QoL/function instruments in 169/392 (43.1%) and MRD/molecular/biomarker procedures in 157/392 (40.1%).
The practical CTIS lesson is to prepare endpoint language as a cross-functional submission asset. Endpoint definitions, assessment windows, adjudication rules, response criteria, MRD methods, safety grading and PRO instruments should be submission-ready before Part I/II coordination, especially for multi-country Phase III trials.
Endpoint-family counts are trial-level presence counts: a trial is counted once for an endpoint family when that family appears in the relevant endpoint field. AE means adverse event; SAE means serious adverse event; TEAE means treatment-emergent adverse event. PFS means progression-free survival; OS means overall survival; EFS means event-free survival; DFS means disease-free survival; RFS means relapse-free survival. ORR means overall or objective response rate; CR means complete response; PR means partial response; VGPR means very good partial response. MRD means minimal residual disease. PK/PD means pharmacokinetic/pharmacodynamic. PRO means patient-reported outcome. QoL means quality of life. VOC means vaso-occlusive crisis. CTIS means Clinical Trials Information System for EU clinical trial submissions.