Across 21 stopped trials of menin, DOT1L, BET, CDK9 and LSD1 inhibitors in acute leukaemia, 12 (57%) were stopped for sponsor or enrolment reasons, and the only two risk-benefit stops are one molecule - failure here has mostly been structural
also called why epigenetic leukaemia trials stop · class-level trial failure atlas
When trials of these epigenetic leukaemia drugs have ended early, it was mostly because a company changed course or too few patients signed up, not because of a stated safety problem. For a disease as rare as infant leukaemia, running out of patients and sponsors is the failure to plan for.
The same thing, for a scientist
Raw ClinicalTrials.gov v2. BET, CDK9 and LSD1 inhibitor searches returned 71, 101 and 41 trials; 34 are acute-leukaemia or MDS trials of a named drug in the class (BET 5, CDK9 19, LSD1 10) of which 14 are stopped (2, 8, 4). With menin and DOT1L (q198: 7 stopped) the pool is 21 stopped trials. Hand-read reasons: business or strategy 10, administrative 3, none stated 2, efficacy or futility 2, accrual or financial 2, risk-benefit 2. Sponsor- or enrolment-driven (business + accrual): 12 (57.1%). Both risk-benefit stops are GSK2879552, an LSD1 inhibitor.
Every stopped trial in the three new classes, verbatim
| NCT | class | status | enrolled | verbatim reason | category |
|---|---|---|---|---|---|
| NCT02303782 | BET bromodomain | withdrawn | 0 | none stated | none stated |
| NCT02698189 | BET bromodomain | terminated | 9 | This study was terminated due to limited efficacy and not due to safety reasons | efficacy / futility |
| NCT00101231 | CDK9 | terminated | 88 | none stated | none stated |
| NCT02520011 | CDK9 | terminated | 104 | Due to slow enrollment, the extensive time projected to conclude the study hypothesis rendered the study no longer reasonably feasible to complete. | accrual / financial |
| NCT03484520 | CDK9 | terminated | 48 | Strategic considerations | business / strategy |
| NCT03547115 | CDK9 | terminated | 84 | Business reasons, not related to safety or efficacy results. | business / strategy |
| NCT03593915 | CDK9 | terminated | 20 | The sponsor decided not to continue the study based on the overall company strategy in AML. | business / strategy |
| NCT03969420 | CDK9 | terminated | 11 | Business decision to terminate the development of alvocidib program on 17 November 2020. Patients permitted on treatment until April 22, 2021. The last end-of-treatment follow-up completed on May 14, 2021. | business / strategy |
| NCT04493099 | CDK9 | withdrawn | 0 | The original sponsor was acquired by a new company and has elected to end funding for all Investigator Sponsored Trials (ISTs) | business / strategy |
| NCT05168904 | CDK9 | suspended | 210 | Slow enrollment and financial limitations | accrual / financial |
| NCT02177812 | LSD1 | terminated | 41 | The risk benefit in relapsed refractory AML does not favor continuation of the study. | risk-benefit |
| NCT02929498 | LSD1 | terminated | 7 | The risk benefit in the study population does not favor continuation of the study | risk-benefit |
| NCT04748848 | LSD1 | terminated | 1 | Business objectives have changed. | business / strategy |
| NCT06514261 | LSD1 | suspended | 45 | Other - Pending amendment for study expansion. | administrative |
Three ways the filter was wrong before it was right
(1) Matching 'leuk' or 'myeloid' alone admitted chronic lymphocytic leukaemia, lymphoma and myeloma trials of the same drugs. (2) A bare 'blast' matched glioblastoma, putting a birabresib glioblastoma trial in the acute-leukaemia set. (3) A regex patched through a shell layer had its \b turned into a backspace character, so it matched no text at all and silently dropped real AML trials - including the dinaciclib+venetoclax trial and the CC-90011 trial. The filter now carries a self-test (it must accept 'Acute Myeloid Leukemia' and reject 'Recurrent Glioblastoma', and its pattern may not contain a backspace) and stops the run if it fails.
What this implies for an infant programme
The dominant way these programmes ended is the least biological. Two CDK9 trials in adult myeloid disease ended for slow enrolment (one with financial limitations); five CDK9 trials and one LSD1 trial ended on business or strategy, one of them because its sponsor was acquired and funded no investigator-sponsored trials. The largest characterised series holds about 1,200 infants accrued over twenty years through referral, which is far harder to enrol than adult AML, so sponsor continuity and enrolment feasibility are the first-order risks to plan for, ahead of any toxicity this registry records.
| script | analyses/q200-how-neighbouring-epigenetic-drug-classes-stopped-in-acute-leukaemia/pull.py then classify.py |
|---|---|
| n stopped | 21 |
per class — the numbers behind the chart
{
"BET bromodomain": {
"relevant": 5,
"stopped": 2,
"completed": 2,
"reasons": {
"none stated": 1,
"efficacy / futility": 1
}
},
"CDK9": {
"relevant": 19,
"stopped": 8,
"completed": 11,
"reasons": {
"none stated": 1,
"accrual / financial": 2,
"business / strategy": 5
}
},
"LSD1": {
"relevant": 10,
"stopped": 4,
"completed": 1,
"reasons": {
"risk-benefit": 2,
"business / strategy": 1,
"administrative": 1
}
},
"menin + DOT1L (q198)": {
"relevant": 62,
"stopped": 7,
"completed": 10,
"reasons": {
"business / strategy": 4,
"efficacy / futility": 1,
"administrative": 2
}
}
}pooled — the numbers behind the chart
{
"none stated": 2,
"efficacy / futility": 2,
"accrual / financial": 2,
"business / strategy": 10,
"risk-benefit": 2,
"administrative": 3
}reason by nct — the numbers behind the chart
{
"NCT02303782": {
"category": "none stated",
"class": "BET bromodomain",
"why_stopped": null,
"enrollment": 0,
"status": "WITHDRAWN",
"title": "A Study Assessing tOTX015 in Combination With Azacitidine (AZA) or AZA Single Agent in Patients With Newly-diagnosed Acute Myeloid Leukemia (AML) Not Candidate for Standard Intensive Induction Therapy (SIIT)"
},
"NCT02698189": {
"category": "efficacy / futility",
"class": "BET bromodomain",
"why_stopped": "This study was terminated due to limited efficacy and not due to safety reasons",
"enrollment": 9,
"status": "TERMINATED",
"title": "A Dose Exploration Study With Birabresib (MK-8628) in Participants With Selected Hematologic Malignancies (MK-8628-005)"
},
"NCT00101231": {
"category": "none stated",
"class": "CDK9",
"why_stopped": null,
"enrollment": 88,
"status": "TERMINATED",
"title": "Flavopiridol in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia"
},
"NCT02520011": {
"category": "accrual / financial",
"class": "CDK9",
"why_stopped": "Due to slow enrollment, the extensive time projected to conclude the study hypothesis rendered the study no longer reasonably feasible to complete.",
"enrollment": 104,
"status": "TERMINATED",
"title": "Alvocidib Biomarker-driven Phase 2 AML Study"
},
"NCT03484520": {
"category": "business / strategy",
"class": "CDK9",
"why_stopped": "Strategic considerations",
"enrollment": 48,
"status": "TERMINATED",
"title": "A Study of Venetoclax and Dinaciclib (MK7965) in Patients With Relapsed/Refractory Acute Myeloid Leukemia"
},
"NCT03547115": {
"category": "business / strategy",
"class": "CDK9",
"why_stopped": "Business reasons, not related to safety or efficacy results.",
"enrollment": 84,
"status": "TERMINATED",
"title": "A Study of Voruciclib Alone or in Combination With Venetoclax in Subjects With B-Cell Malignancies or AML"
},
"NCT03593915": {
"category": "business / strategy",
"class": "CDK9",
"why_stopped": "The sponsor decided not to continue the study based on the overall company strategy in AML.",
"enrollment": 20,
"status": "TERMINATED",
"title": "A Phase 1b/2 Study of Alvocidib Plus Decitabine or Azacitidine in Patients With MDS"
},
"NCT03969420": {
"category": "business / strategy",
"class": "CDK9",
"why_stopped": "Business decision to terminate the development of alvocidib program on 17 November 2020. Patients permitted on treatment until April 22, 2021. The last end-of-treatment follow-up completed on May 14, 2021.",
"enrollment": 11,
"status": "TERMINATED",
"title": "Study of Alvocidib in Patients With Relapsed/Refractory AML Following Treatment With Venetoclax Combination Therapy"
},
"NCT04493099": {
"category": "business / strategy",
"class": "CDK9",
"why_stopped": "The original sponsor was acquired by a new company and has elected to end funding for all Investigator Sponsored Trials (ISTs)",
"enrollment": 0,
"status": "WITHDRAWN",
"title": "Alvocidib in Combination With Decitabine and Venetoclax in Patients With Relapsed or Refractory AML or as Frontline Therapy in Unfit Patients With AML"
},
"NCT05168904": {
"category": "accrual / financial",
"class": "CDK9",
"why_stopped": "Slow enrollment and financial limitations",
"enrollment": 210,
"status": "SUSPENDED",
"title": "A Study to Investigate Fadraciclib (CYC065), in Subjects With Leukemia or Myelodysplastic Syndrome (MDS)"
},
"NCT02177812": {
"category": "risk-benefit",
"class": "LSD1",
"why_stopped": "The risk benefit in relapsed refractory AML does not favor continuation of the study.",
"enrollment": 41,
"status": "TERMINATED",
"title": "A Phase I Dose Escalation Study of GSK2879552 in Subjects With Acute Myeloid Leukemia (AML)"
},
"NCT02929498": {
"category": "risk-benefit",
"class": "LSD1",
"why_stopped": "The risk benefit in the study population does not favor continuation of the study",
"enrollment": 7,
"status": "TERMINATED",
"title": "Safety, Clinical Activity, Pharmacokinetics (PK) and Pharmacodynamics Study of GSK2879552, Alone or With Azacitidine, in Subjects With High Risk Myelodysplastic Syndromes (MDS)"
},
"NCT04748848": {
"category": "business / strategy",
"class": "LSD1",
"why_stopped": "Business objectives have changed.",
"enrollment": 1,
"status": "TERMINATED",
"title": "A Safety, Tolerability and Preliminary Efficacy Study of CC-90011 in Combination With Venetoclax and Azacitidine in R/R Acute Myeloid Leukemia and Treatment-naïve Participants Not Eligible for Intensive Therapy"
},
"NCT06514261": {
"category": "administrative",
"class": "LSD1",
"why_stopped": "Other - Pending amendment for study expansion.",
"enrollment": 45,
"status": "SUSPENDED",
"title": "Testing the Combination of an Anti-Cancer Drug, Iadademstat, With Other Anti-Cancer Drugs (Venetoclax and Azacitidine) for Treating AML"
}
}- Plan for the structural failure first. An infant KMT2A-rearranged programme dependent on one industry sponsor and one enrolling network has the profile of the CDK9 programmes that ended in 'strategy' and 'slow enrollment'; a cooperative-group fallback and multi-country enrolment are mitigations, and neither is evidence-backed here.
- How many of the sponsor exits were followed by another sponsor taking the molecule forward? A trial stopped for 'strategy' is a different loss if the drug lives on.
- Do cooperative groups (Interfant, COG) have a record of finishing trials that industry sponsors abandoned, which would argue for a non-industry fallback for infant protocols?
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
Searches of the raw ClinicalTrials.gov registry for BET, CDK9 and LSD1 inhibitors returned 71, 101 and 41 trials; under a declared rule (a named class drug as an intervention, and acute leukaemia or MDS in the title or a short condition list) 34 are relevant: BET 5, CDK9 19, LSD1 10.
ClinicalTrials.gov API v2 (raw, so whyStopped is present), pulled 2026-10-06 by analyses/q200-how-neighbouring-epigenetic-drug-classes-stopped-in-acute-leukaemia/pull.py · ClinicalTrials.gov 2026What this evidence cannot show
totalCount asserted equal to rows returned for each search. Excluded on purpose: solid-tumour, lymphoma, myeloma, CLL and myelofibrosis trials of the same drugs (e.g. pelabresib in myelofibrosis), and trials whose only acute-leukaemia tag sits in a condition list of more than eight entries (NCI-PDQ boilerplate).
Evidence that argues against this (1)
- The rule is mine and built on named drugs: a compound in the class that I did not name is missed, and a trial of a listed drug in a mixed 'haematological malignancies' population with no acute-leukaemia term in its title or short condition list is excluded. Counts describe REGISTERED trials only. ClinicalTrials.gov 2026
- E2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
Of 21 stopped trials across the five classes (menin, DOT1L, BET, CDK9, LSD1) in acute leukaemia and MDS, 10 cite business or strategy, 3 administrative reasons, 2 efficacy or futility, 2 accrual or finances, 2 give no reason and 2 state a risk-benefit judgement; 12 (57.1%) were therefore sponsor- or enrolment-driven.
ClinicalTrials.gov API v2 (raw, so whyStopped is present), pulled 2026-10-06 by analyses/q200-how-neighbouring-epigenetic-drug-classes-stopped-in-acute-leukaemia/pull.py · ClinicalTrials.gov 2026What this evidence cannot show
Each of the 21 verbatim strings was read and categorised by hand (14 here, 7 in q198). One string, 'Business reasons, not related to safety or efficacy results', explicitly denies the other two readings; most others are silent on them.
Evidence that argues against this (1)
- A stated business or strategy reason can sit on top of disappointing data that the sponsor does not record; only one of the ten explicitly rules safety and efficacy out. The classes also differ in era (CDK9 trials from 2004 to 2021) and sponsor type, and n = 21 gives no rate with a usable interval. ClinicalTrials.gov 2026
- E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
Two CDK9-inhibitor trials in adult myeloid disease were stopped for slow enrolment - the biomarker-driven alvocidib phase 2 in AML (n = 104, terminated) and fadraciclib in leukaemia or MDS (n = 210, suspended, 'slow enrollment and financial limitations').
ClinicalTrials.gov API v2 (raw, so whyStopped is present), pulled 2026-10-06 by analyses/q200-how-neighbouring-epigenetic-drug-classes-stopped-in-acute-leukaemia/pull.py · ClinicalTrials.gov 2026What this evidence cannot show
Verbatim: 'Due to slow enrollment, the extensive time projected to conclude the study hypothesis rendered the study no longer reasonably feasible to complete' and 'Slow enrollment and financial limitations'.
Evidence that argues against this (1)
- 'Slow enrolment' is the sponsor's summary, not a cause: it often reflects restrictive eligibility, a biomarker requirement or competing studies in a crowded adult-AML field. The inference that an infant-scale population would fare worse is mine and rests on the relative sizes of the populations, not on these trials. ClinicalTrials.gov 2026
LSD1 class stop reasons
CDK9 class stop reasons
- related to →BET bromodomain inhibition in KMT2A-rearranged leukemia — spectacular preclinically, stalled clinically
BET class stop reasons
menin class stop reasons (q198)
- related to →Pinometostat (EPZ-5676) — the DOT1L inhibitor, and the most instructive failure in this field
DOT1L class stop reason (q198)
CDK9 programmes ended by strategy and enrolment