Of 62 registered menin- or DOT1L-inhibitor trials, 7 have stopped and none gave a safety reason - four were company or supply decisions - yet the same drugs carry dose-limiting differentiation syndrome and QT prolongation that the registry never mentions
also called why menin inhibitor trials stop · registry stop reasons · whyStopped analysis
Seven trials of menin or DOT1L drugs have been stopped early, and none of them said a safety problem was why - most were company decisions. But the published papers show these drugs do cause serious side effects, so the registry's silence tells you almost nothing about safety.
The same thing, for a scientist
Raw ClinicalTrials.gov v2 (the MCP wrapper omits whyStopped). Five searches returned 576 trials; a declared rule keeps 119 as relevant, of which 62 name a menin or DOT1L inhibitor. Of those, 7 are stopped (3 withdrawn before enrolling, 4 terminated). Hand-read reasons: 4 supply or business, 2 administrative, 1 futility in a solid-tumour cohort outside the indication, 0 safety. The two published safety sources below report grade >=3 differentiation syndrome of 13-15% and grade 3/4 QT prolongation of 12% - none of which is a registry stop reason.
What was counted, and the filter that mattered
Five searches (KMT2A/MLL conditions; menin-inhibitor interventions; DOT1L-inhibitor interventions; infant leukaemia; free-text KMT2A-rearranged) returned 576 distinct trials. A first pass that treated every KMT2A mention as relevant kept 194 'KMT2A-labelled' trials and reported a 22.6% stopped rate - but 148 of them are NCI-PDQ records whose tag 'Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities' is one AML subtype in a list of up to 14, i.e. trials of AML of any kind. They are now counted separately (174) and excluded. What remains: 119 relevant, 62 mechanism-targeted.
Every stopped mechanism-targeted trial, verbatim
| NCT | status | enrolled | verbatim reason | category |
|---|---|---|---|---|
| NCT03724084 | terminated | 6 | Other - Study agent no longer available | supply / business |
| NCT05153330 | terminated | 55 | Biomea Fusion, Inc., is no longer pursuing oncology indications for BMF-219. No safety concerns or efficacy observations led to this study closure. | supply / business |
| NCT05521087 | withdrawn | 0 | Business Decision | supply / business |
| NCT05631574 | terminated | 13 | Biomea Fusion, Inc., is no longer pursuing oncology indications for BMF-219. No safety concerns or efficacy observations led to this study closure. | supply / business |
| NCT05731947 | terminated | 41 | Study was terminated by sponsor after Phase 1b as pre-defined signals of efficacy were not met in the Phase 1b dose expansion cohort. | futility |
| NCT07052994 | withdrawn | 0 | PI requested | administrative |
| NCT07498465 | withdrawn | 0 | Other - Protocol moved to Withdrawn | administrative |
Why 'no safety reason' is not 'safe'
whyStopped is voluntary free text, and a safety problem that is managed rather than fatal to a programme never appears in it. The clinical papers report it plainly: grade >=3 differentiation syndrome in 12 of 83 patients (15%) with two treatment-related deaths on ziftomenib, and grade 3/4 QT prolongation in 12%, called the primary dose-limiting effect, on revumenib. Neither stopped a trial. A registry-based reading of this field would have concluded the opposite of what the clinicians know.
| script | analyses/q198-the-registry-of-stopped-trials/pull.py then analyze.py |
|---|---|
| pulled | 576 |
strata — the numbers behind the chart
{
"T2b subtype-tag only (not KMT2A-targeted)": 174,
"EXCLUDED (retrieved but not relevant)": 283,
"T1 mechanism-targeted": 62,
"T2 KMT2A-labelled": 18,
"T4 text mention only": 11,
"T3 infant leukaemia": 28
}rates by stratum — the numbers behind the chart
{
"T1 mechanism-targeted": {
"stopped": 7,
"completed": 10,
"rate": 0.412,
"n": 62
},
"T2 KMT2A-labelled": {
"stopped": 1,
"completed": 5,
"rate": 0.167,
"n": 18
},
"T3 infant leukaemia": {
"stopped": 0,
"completed": 13,
"rate": 0,
"n": 28
},
"T4 text mention only": {
"stopped": 0,
"completed": 4,
"rate": 0,
"n": 11
},
"class: menin inhibitor": {
"stopped": 6,
"completed": 7,
"rate": 0.462,
"n": 58
},
"class: DOT1L inhibitor": {
"stopped": 1,
"completed": 3,
"rate": 0.25,
"n": 4
},
"ALL RELEVANT": {
"stopped": 8,
"completed": 32,
"rate": 0.2,
"n": 119
}
}t1 reasons — the numbers behind the chart
{
"supply / business": 4,
"futility": 1,
"administrative": 2
}reason by nct
{
"NCT03724084": {
"category": "supply / business",
"why_stopped": "Other - Study agent no longer available"
},
"NCT05153330": {
"category": "supply / business",
"why_stopped": "Biomea Fusion, Inc., is no longer pursuing oncology indications for BMF-219. No safety concerns or efficacy observations led to this study closure."
},
"NCT05631574": {
"category": "supply / business",
"why_stopped": "Biomea Fusion, Inc., is no longer pursuing oncology indications for BMF-219. No safety concerns or efficacy observations led to this study closure."
},
"NCT05521087": {
"category": "supply / business",
"why_stopped": "Business Decision"
},
"NCT05731947": {
"category": "futility",
"why_stopped": "Study was terminated by sponsor after Phase 1b as pre-defined signals of efficacy were not met in the Phase 1b dose expansion cohort."
},
"NCT07052994": {
"category": "administrative",
"why_stopped": "PI requested"
},
"NCT07498465": {
"category": "administrative",
"why_stopped": "Other - Protocol moved to Withdrawn"
},
"NCT02419755": {
"category": "accrual / feasibility",
"why_stopped": "Accrual goals were no longer feasible based on restrictions imposed by the DSMB."
}
}recall missing
{
"NCT03792256": "AINV18P1 palbociclib COG",
"NCT01319864": "POE 10-03 plerixafor"
}- Reading 'no trial stopped for safety' as 'safe' would under-prepare any infant protocol: differentiation syndrome and QT prolongation are dose-limiting class signals that closed no trial (E3, E4). Plan monitoring from the clinical papers, not from the registry.
- Do the posted results/adverse-event tables of the completed menin-inhibitor trials report infants separately, and how many infants contributed to the differentiation-syndrome and QT figures?
- Which of the four business stops were paediatric-first programmes, and did any leave a population with no remaining menin-inhibitor trial?
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
A raw ClinicalTrials.gov v2 pull of five searches returned 576 distinct trials; under a declared rule 119 are relevant and 62 name a menin or DOT1L inhibitor as an intervention, while 174 records that name KMT2A only inside a long subtype list were excluded as not KMT2A-targeted.
ClinicalTrials.gov API v2 (raw, so whyStopped is present), pulled 2026-10-06 by analyses/q198-the-registry-of-stopped-trials/pull.py · ClinicalTrials.gov 2026What this evidence cannot show
RECALL CHECKED BEFORE COUNTING: the pull found 9 of the 11 trials this corpus had already verified; the two missed (NCT03792256, NCT01319864) are general relapsed-leukaemia trials whose registry records do not name KMT2A in title, conditions or eligibility text, so a KMT2A search cannot find them. totalCount was asserted equal to the rows returned for every search (an earlier version silently skipped that check).
Evidence that argues against this (1)
- The relevance rule is mine and is a choice: a trial in KMT2A-rearranged patients that names neither KMT2A in its title/conditions nor a menin or DOT1L inhibitor as an intervention is not retrieved. Counts are of REGISTERED trials; unregistered or non-US-registered work is invisible. ClinicalTrials.gov 2026
- E2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
Of the 62 mechanism-targeted trials, 7 are stopped - three withdrawn before enrolling anyone and four terminated - for supply or business reasons (4), administrative reasons (2) and futility in a colorectal and other solid-tumour cohort outside the indication (1); none cites a safety reason, and one sponsor statement says in terms that no safety concerns or efficacy observations led to closure.
ClinicalTrials.gov API v2 (raw, so whyStopped is present), pulled 2026-10-06 by analyses/q198-the-registry-of-stopped-trials/pull.py · ClinicalTrials.gov 2026What this evidence cannot show
Each of the seven verbatim strings was READ and categorised by hand (a keyword rule would have filed Biomea's 'No safety concerns or efficacy observations' under both safety and efficacy). n = 7, so no rate is claimed.
Evidence that argues against this (1)
- Absence of a stated safety reason is not absence of a safety signal. The field is voluntary, short, and written by the sponsor; a programme that mitigates a toxicity (dose, prophylaxis, monitoring) rather than closing never records it there. E3 and E4 are the same drug class reporting the toxicities the registry does not. ClinicalTrials.gov 2026
- E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
In the KOMET-001 phase 1 of ziftomenib in relapsed or refractory AML, grade 3 or worse differentiation syndrome occurred in 12 of 83 patients (15%), and two treatment-related deaths were reported (one differentiation syndrome, one cardiac arrest).
Ziftomenib in relapsed or refractory acute myeloid leukaemia (KOMET-001): a multicentre, open-label, multi-cohort, phase 1 trial · Lancet Oncol 2024What this evidence cannot show
Read from the raw PubMed XML abstract 2026-10-06. Adults with relapsed or refractory AML in a dose-escalation and expansion design.
Evidence that argues against this (1)
- Adult relapsed/refractory phase 1 data: the rates in infants, in frontline combinations, and with different prophylaxis are not given by this paper. The programme continued (several ziftomenib trials are open), which is the point: a serious on-target toxicity did not close a trial. Lancet Oncol 2024
- E4moderate confidence 3 of 5: One strong study, or several smaller consistent ones.review
Grade 3/4 QT prolongation, reported as the primary dose-limiting adverse effect of revumenib, occurred in 12% of patients, and grade 3/4 differentiation syndrome in 13%.
Revumenib for Relapsed or Refractory Acute Leukemia With a KMT2A Translocation · Ann Pharmacother 2025What this evidence cannot show
A pharmacotherapy review of the approval data, so a SECONDARY source for the rates; read from the raw PubMed XML abstract 2026-10-06.
Evidence that argues against this (1)
- Review-level source; the primary AUGMENT-101 report and the prescribing information are the authority for the exact figures, and the population is relapsed/refractory adults and children together. Ann Pharmacother 2025
revumenib stop reasons and class toxicities
ziftomenib differentiation syndrome in KOMET-001
JNJ-75276617 paediatric trial withdrawn for a business decision
- related to →Pinometostat (EPZ-5676) — the DOT1L inhibitor, and the most instructive failure in this field
pinometostat trial terminated, agent no longer available
AUGMENT-101 admits infants from 30 days