Only 4 of 43 open menin- or DOT1L-inhibitor trials admit infants under one year (9.3%), and only one (TINI-2) is infant-specific, though infants are about a third of the characterised KMT2A-rearranged population
Almost all the open trials of the new menin-blocking drugs exclude babies, though babies make up about a third of KMT2A-rearranged leukaemia in the largest patient series. Only one of the four trials that do admit infants is built around them.
The same thing, for a scientist
Open mechanism-targeted trials by minimum age (registry minimumAge; a MISSING minimum means no lower limit): under 1 year 4 of 43 (9.3%), 1-17 years 15, 18 and over 24. The four are AUGMENT-101, a COG revumenib protocol, TINI-2 and a ziftomenib paediatric trial. Against this, infants (<=12 months, ALL plus AML) are 1184 of 3,401 (34.8%) in the 2023 recombinome cohort, a REFERRAL cohort.
The four, from the registry
| NCT | status | minimum age | enrolment | sponsor |
|---|---|---|---|---|
| NCT05761171 | active_not_recruiting | 1 Month | 78 | Children's Oncology Group |
| NCT06376162 | recruiting | 0 Years | 20 | PedAL BCU, LLC |
| NCT04065399 | recruiting | 30 Days | 447 | Syndax Pharmaceuticals |
| NCT05848687 | recruiting | none stated (no lower limit) | 90 | Tanja Andrea Gruber |
A bug that hid one of them
A first pass bucketed a missing minimumAge as 'not stated' and so omitted TINI-2, a trial with a menin inhibitor and a maximum age of one year - the ledger had already verified it. In ClinicalTrials.gov a missing minimum means no lower limit. The bucket now treats it that way, and the sanity check against an already-verified trial is what caught it.
| script | analyses/q198-the-registry-of-stopped-trials/analyze.py |
|---|
age t1 all — the numbers behind the chart
{
"18 years and over": 36,
"under 1 year (infants)": 10,
"1-17 years": 16
}age t1 open — the numbers behind the chart
{
"18 years and over": 24,
"under 1 year (infants)": 4,
"1-17 years": 15
}open infant trials — the numbers behind the chart
[
{
"nct": "NCT05761171",
"status": "ACTIVE_NOT_RECRUITING",
"min_age": "1 Month",
"enrollment": 78,
"sponsor": "Children's Oncology Group",
"title": "A Study of Revumenib in Combination With Chemotherapy for Patients Diagnosed With Relapsed or Refractory Leukemia"
},
{
"nct": "NCT06376162",
"status": "RECRUITING",
"min_age": "0 Years",
"enrollment": 20,
"sponsor": "PedAL BCU, LLC",
"title": "Ziftomenib in Combination With Chemotherapy for Children With Relapsed/Refractory Acute Leukemia"
},
{
"nct": "NCT04065399",
"status": "RECRUITING",
"min_age": "30 Days",
"enrollment": 447,
"sponsor": "Syndax Pharmaceuticals",
"title": "A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation"
},
{
"nct": "NCT05848687",
"status": "RECRUITING",
"min_age": null,
"enrollment": 90,
"sponsor": "Tanja Andrea Gruber",
"title": "TINI 2: Total Therapy for Infants With Acute Lymphoblastic Leukemia II"
}
]phase t1 — the numbers behind the chart
{
"PHASE1": 30,
"PHASE3": 5,
"PHASE2": 11,
"PHASE1/PHASE2": 13,
"none": 2,
"PHASE2/PHASE3": 1
}- Evidence that a menin inhibitor works, and how toxic it is, comes overwhelmingly from adults. Differentiation syndrome and QT management in infants, whose marrow, drug clearance and cardiac reserve differ, is extrapolated rather than measured.
- How many infants have actually been enrolled across these four trials? The registry gives enrolment, not age mix of enrolled patients.
- Does any open mechanism-targeted trial carry an infant-specific stratum or cohort in its design even though its minimum age is higher?
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
Of 43 open mechanism-targeted trials (recruiting, not yet recruiting, active, or enrolling by invitation), 4 (9.3%) admit infants under one year: NCT05761171, NCT06376162, NCT04065399, NCT05848687; TINI-2 is the only one restricted to infants (maximum age one year).
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
Computed from the pull, with a missing minimumAge read as no lower limit. TINI-2 lists these interventions: Dexamethasone, Mitoxantrone, PEG asparaginase, Bortezomib, Vorinostat, Mercaptopurine, Methotrexate, Blinatumomab, Ziftomenib.
Evidence that argues against this (1)
- 'Admits infants' is eligibility, not enrolment. AUGMENT-101 (n=447) admits infants from 30 days but its enrolment is dominated by adults, so the number of infants actually treated in these four trials is unknown and far smaller than their enrolment suggests. ClinicalTrials.gov 2026
- E2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
Infants (12 months or younger, ALL plus AML) are 1184 of the 3,401 genomically characterised KMT2A-rearranged patients (34.8%), against 9.3% of open mechanism-targeted trials that admit them.
The KMT2A recombinome of acute leukemias in 2023. · Meyer C, Larghero P, Almeida Lopes B, Burmeister T, Gröger D, Sutton R, Venn NC, Cazzaniga G, Corral Abascal L, Tsaur G, Fechina L, Emerenciano M, Pombo-de-Oliveira MS, et al., Marschalek R · Leukemia 37:988-1005 2023What this evidence cannot show
Infant ALL 987 and infant AML 197 are the age-lineage strata of the 2023 recombinome, transcribed from this corpus's breakpoint-kmt2a-partner-frequency-by-age-lineage entry. THEY ARE NOT IN THE ABSTRACT (checked 2026-10-06: the abstract carries only the 3401 total), so they sit in the paper's body or tables, which were not re-read here.
Evidence that argues against this (1)
- The cohort is a REFERRAL cohort (DCAL Frankfurt, 20 countries, 2003-2022), not a population sample, so 34.8% is the composition of KMT2A-rearranged disease in that series and not an incidence; and 'admits' versus 'is the age mix' are different quantities. The comparison shows a mismatch in kind, not a measured shortfall. Meyer C et al. 2023
admits infants but enrolment dominated by adults
- related to →Interfant-21 (NCT05327894) — the randomised test of blinatumomab in infant KMT2A-rearranged ALL, open now
infant randomised trial context
- related to →Which partner, in which patient: KMT2A partner frequencies across six age-lineage strata
infant share of the characterised cohort