Registry sweep: is there any CXCR4-directed trial in KMT2A-rearranged or infant leukaemia? There is not, and the one paediatric attempt closed with a single patient
also called CXCR4 trial landscape sweep · plerixafor in KMT2A-rearranged leukaemia registry search
We searched the public register of clinical trials for any study that blocks the CXCR4 receptor in children with this genetic type of leukaemia, or in infants at all. There is none — the nearest thing is a trial that opened in 2012, enrolled one child, and closed for lack of patients.
The same thing, for a scientist
A raw ClinicalTrials.gov v2 API sweep on 2026-09-19 for CXCR4-directed interventions (plerixafor, AMD3100, motixafortide/BL-8040, ulocuplumab/BMS-936564, mavorixafor, LY2510924, POL6326, POL5551, burixafor, balixafortide, or the bare term CXCR4) against KMT2A/MLL/mixed-lineage-leukaemia terms returned **one** record, and it is a donor stem-cell mobilization study in which 'Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities' appears only as one of 80-odd condition terms; it was TERMINATED with n=1 and whyStopped 'Funding withdrawal' [E1]. The same interventions against paediatric AML (maximum age <=21 years) returned **two** records, both transplant-conditioning or mobilization studies, neither therapeutic against KMT2A-rearranged disease [E2]. Against acute lymphoblastic leukaemia generally there are 23 records, overwhelmingly donor mobilization and transplant conditioning; the therapeutic ones are adult (motixafortide plus nelarabine in T-ALL, TERMINATED for low accrual; ulocuplumab phase 1 in adult relapsed AML) [E2]. The only completed paediatric therapeutic study is POE 10-03 (`trial-poe-10-03-plerixafor-paediatric`), whose minimum age was 3 years. **Conclusion: the CXCR4 hypothesis in KMT2A-rearranged and infant leukaemia has never been tested clinically.** The closest attempt, NCT01655875, a pilot of AMD3100 as a sensitizing agent in myeloablative allogeneic transplant for chemotherapy-resistant paediatric acute leukaemia, was TERMINATED with **one patient enrolled** and whyStopped **'lack of patient enrollment'** [E3].
Method
All queries went to the raw v2 API (https://clinicaltrials.gov/api/v2/studies), not the MCP tool, because the MCP tool does not return whyStopped and this project has previously written 'the registry gives no reason' about a record where the registry gives the reason plainly.
Fields requested: identification, status (including whyStopped), design, conditions, eligibility and arms/interventions. Intervention half held constant across queries as the CXCR4-directed agent list above; condition/term half varied.
| query | result |
|---|---|
| CXCR4 agents x term KMT2A/MLL/'mixed lineage leukemia' | 1 record, NCT01076270, donor PBSC mobilization, TERMINATED n=1, whyStopped 'Funding withdrawal'; the MLL term is one of ~80 condition strings |
| CXCR4 agents x condition AML, max age <=21 y | 2 records: NCT01068301 (plerixafor-containing regimen, second allo-SCT, COMPLETED n=12) and NCT01621477 (haplo-HSCT + NK cells with plerixafor among nine interventions, TERMINATED, 'replaced by a new study') |
| CXCR4 agents x condition acute lymphoblastic leukaemia | 23 records, mostly donor mobilization and transplant conditioning |
No query returned a therapeutic trial of CXCR4 blockade in KMT2A-rearranged leukaemia, in infant leukaemia, or in any paediatric population outside the transplant setting except POE 10-03.
The withdrawn-and-terminated records, which are where the information is
Three whyStopped strings were read and none of them appears in any paper:
- NCT01655875 — A Pilot Study of AMD3100 as a Sensitizing Agent in Myeloablative Allogeneic Blood and Marrow Transplantation for Chemotherapy Resistant Pediatric Acute Leukemia, Emory University, ages 2-22, started 2012-06, completed 2014-04. TERMINATED, actual enrolment 1, whyStopped: 'lack of patient enrollment' 3. This is the closest anyone has come to testing niche disruption in chemotherapy-resistant paediatric leukaemia, and it closed with one patient.
- NCT02763384 — motixafortide (BL-8040) plus nelarabine in relapsed/refractory T-ALL, adults, TERMINATED, whyStopped 'Low accrual' 2.
- NCT01076270 — plerixafor and filgrastim for donor PBSC mobilization, TERMINATED n=1, whyStopped 'Funding withdrawal' 1.
The pattern is consistent and is itself the finding: CXCR4-directed trials in leukaemia fail to accrue. Two of the three closures are accrual failures and one is funding. None is a safety or efficacy signal. That distinction matters, because 'CXCR4 antagonism has not worked in leukaemia' and 'CXCR4 antagonism has not been adequately tested in leukaemia' lead to different decisions, and the registry says the second.
What this means for the beat's question
The dispatch asked whether CXCR4 inhibition is a real option in KMT2A-rearranged or infant leukaemia. The registry answer is that it is an untested one, and that the two attempts to test something adjacent to it both closed for want of patients rather than for want of effect.
The preclinical case is genuinely strong and genuinely specific to this genotype: primary infant KMT2A-rearranged ALL is differentially protected by stroma relative to non-rearranged ALL, and CXCR4 antagonism reverses it (recorded in mechanism-kmt2a-r-tissue-localization). The clinical case is one phase 1 in older children that engaged its target and produced three responses in eighteen, none in ALL (trial-poe-10-03-plerixafor-paediatric).
And there is a mechanistic reason for caution that is independent of the trials: in murine MLL-AF9 AML, CXCR4 is essential independently of CXCL12, and Cxcr4 deletion eradicates leukaemia without impairing marrow homing (mechanism-cxcl12-cxcr4-marrow-retention). If the requirement is cell-intrinsic signalling rather than niche retention, a ligand-blocking antagonist like plerixafor may not reproduce the genetic phenotype at all — which would explain a trial that mobilised cells successfully and did little else.
| script | ad hoc raw ClinicalTrials.gov v2 API queries; parameters recorded in the Method section |
|---|---|
| status | run |
| run date | 2026-09-19 |
| result summary | No CXCR4-directed trial exists in KMT2A-rearranged or infant leukaemia. One record matches KMT2A/MLL terms and it is an incidental condition string on a terminated donor-mobilization study. Paediatric CXCR4 use is confined to transplant mobilization and conditioning, plus the single completed therapeutic study POE 10-03 (minimum age 3 years). The three terminations read all cite accrual or funding, never safety or efficacy. |
| conclusion | the CXCR4 hypothesis in KMT2A-rearranged and infant leukaemia is untested, not refuted |
| method note | raw v2 API used throughout so that whyStopped was returned; the Clinical_Trials MCP tool omits that field |
inputs
[ "https://clinicaltrials.gov/api/v2/studies (API v2)", "intervention terms: plerixafor, AMD3100, CXCR4, motixafortide, BL-8040, ulocuplumab, mavorixafor, balixafortide, LY2510924, POL6326, POL5551, burixafor", "term/condition halves: KMT2A OR MLL OR 'mixed lineage leukemia'; acute myeloid leukemia (max age 21 y); acute lymphoblastic leukemia" ]
records of note — the numbers behind the chart
[
{
"nct": "NCT01319864",
"status": "COMPLETED",
"n": 20,
"note": "POE 10-03; the only completed paediatric therapeutic study; min age 3 y",
"why_stopped": null
},
{
"nct": "NCT01655875",
"status": "TERMINATED",
"n": 1,
"note": "AMD3100 sensitisation before allo-BMT in chemoresistant paediatric acute leukaemia",
"why_stopped": "lack of patient enrollment"
},
{
"nct": "NCT02763384",
"status": "TERMINATED",
"n": 12,
"note": "BL-8040 plus nelarabine, adult R/R T-ALL",
"why_stopped": "Low accrual"
},
{
"nct": "NCT01076270",
"status": "TERMINATED",
"n": 1,
"note": "plerixafor/filgrastim donor mobilization; MLL term incidental among ~80 conditions",
"why_stopped": "Funding withdrawal"
},
{
"nct": "NCT01120457",
"status": "COMPLETED",
"n": 96,
"note": "ulocuplumab (BMS-936564) anti-CXCR4 phase 1, adult relapsed AML and B-cell malignancies",
"why_stopped": null
},
{
"nct": "NCT01068301",
"status": "COMPLETED",
"n": 12,
"note": "paediatric plerixafor-containing regimen, second allo-SCT",
"why_stopped": null
}
]- A registry sweep can only find what sponsors registered and labelled; an absence here is weaker evidence than an absence in a literature search, and this entry should not be cited as proof that nobody has tried.
- If a CXCR4 trial were opened in infants it would mobilise blasts in a population already at risk of hyperleukocytosis and leukostasis, and the safety case would have to be made before the efficacy case.
- The repeated accrual failures suggest that even a well-designed CXCR4 study in this population may be undeliverable outside a large cooperative group, which is a practical constraint on any recommendation this graph makes.
- Would an Interfant-style cooperative-group trial be able to accrue a CXCR4 arm in infant KMT2A-rearranged ALL, given that the two single-centre attempts in paediatric leukaemia both closed for accrual?
- Do any of the 23 ALL records enrol KMT2A-rearranged patients without listing the genotype? Registry condition strings rarely carry fusion genotypes, so the absence measured here is an upper bound.
- Is motixafortide, now further developed than plerixafor, a better candidate for a paediatric therapeutic trial, and has anyone filed a paediatric investigation plan for it?
- The three terminations are all accrual or funding. Is there any unpublished safety signal for CXCR4 antagonism in children that would explain the field's reluctance, or is this simply a drug whose commercial owner had no reason to develop it therapeutically?
- E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registry
A ClinicalTrials.gov v2 API query with intervention terms plerixafor, AMD3100, CXCR4, motixafortide, BL-8040, ulocuplumab, mavorixafor, balixafortide, LY2510924, POL6326 or burixafor and term KMT2A OR MLL OR 'mixed lineage leukemia' returns a single record, NCT01076270, a donor peripheral-blood-stem-cell mobilization study using plerixafor and filgrastim in which 'Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities' is one of approximately eighty listed conditions; the record is TERMINATED with an actual enrolment of 1 and whyStopped 'Funding withdrawal'.
ClinicalTrials.gov API v2 query: CXCR4-directed interventions intersected with KMT2A/MLL terms, returning NCT01076270 only · ClinicalTrials.gov (NIH/NLM) · ClinicalTrials.gov 2026What this evidence cannot show
Registry search depends on sponsor-supplied condition and intervention strings. A trial that enrolled KMT2A-rearranged patients without listing the genotype as a condition would be missed, and most paediatric leukaemia trials do not list fusion genotypes. This is therefore an upper bound on absence, not a proof of it, and it says nothing about unregistered or investigator-initiated work. Query run 2026-09-19 against the raw v2 API.
Evidence that argues against this (1)
- Registry absence is not literature absence, and the preclinical case in this exact genotype is strong: primary infant MLL-rearranged ALL is differentially protected by stroma relative to non-MLL-rearranged ALL, protection is conferred by soluble stromal factors alone, stroma protects both bulk blasts and the leukaemia stem cell fraction, and CXCR4 inhibition with AMD3100 markedly enhanced drug efficacy in a xenograft model. The gap is in trials, not in rationale. Read: abstract only. Sison EA et al. 2013
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registry
The same CXCR4-directed intervention list against condition 'acute myeloid leukemia' restricted to maximum age 21 years returns two records, NCT01068301 (a pediatric plerixafor-containing regimen in second allogeneic stem cell transplantation, COMPLETED, n=12) and NCT01621477 (T-cell replete haploidentical HSCT plus NK cells with plerixafor among nine interventions, TERMINATED, whyStopped 'Study was terminated in August 2016 due to replacement by a new study'); against condition 'acute lymphoblastic leukemia' it returns 23 records dominated by donor mobilization and transplant conditioning, whose therapeutic entries are adult - NCT02763384, BL-8040 plus nelarabine in relapsed/refractory T-ALL, TERMINATED with whyStopped 'Low accrual', and NCT01120457, a Bristol-Myers Squibb phase 1 of the anti-CXCR4 antibody BMS-936564 in relapsed AML and selected B-cell malignancies, COMPLETED n=96, adults only.
ClinicalTrials.gov API v2 queries: CXCR4-directed interventions by condition (paediatric AML, n=2; acute lymphoblastic leukaemia, n=23), with whyStopped read on every non-active record · ClinicalTrials.gov (NIH/NLM) · ClinicalTrials.gov 2026What this evidence cannot show
The paediatric filter used the registry's MaximumAge field, which many records leave unset or set inconsistently, so paediatric trials can be missed. Condition strings are sponsor-supplied. Counts are as of 2026-09-19 and will drift. Read: full registry records for the fields quoted.
Evidence that argues against this (1)
- A registry dominated by mobilization and transplant-conditioning uses of plerixafor is evidence about how the drug has been developed, not about whether the biology holds. Plerixafor's licensed indication is stem-cell mobilization, so commercial and investigator incentives have pushed it towards that use; the absence of therapeutic trials reflects development history at least as much as scientific judgement. The only completed paediatric therapeutic study, POE 10-03, showed the drug engages its target in children with leukaemia. Cooper TM et al. 2017
- E3established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registry
NCT01655875, 'A Pilot Study of AMD3100 as a Sensitizing Agent in Myeloablative Allogeneic Blood and Marrow Transplantation for Chemotherapy Resistant Pediatric Acute Leukemia', sponsored by Emory University, eligibility 2 to 22 years, started 2012-06 and completed 2014-04, is TERMINATED with an actual enrolment of 1 and whyStopped 'lack of patient enrollment'.
NCT01655875 - A Pilot Study of AMD3100 as a Sensitizing Agent in Myeloablative Allogeneic Blood and Marrow Transplantation for Chemotherapy Resistant Pediatric Acute Leukemia · Emory University · ClinicalTrials.gov 2014What this evidence cannot show
A single-patient termination tells you about feasibility at one centre in one period, not about the intervention. 'Lack of patient enrollment' is the sponsor's own wording and does not distinguish between an eligibility criterion too narrow to fill, a competing trial, or loss of investigator interest. Retrieved from the raw v2 API on 2026-09-19 so that whyStopped was visible. Read: full registry record.
Evidence that argues against this (1)
- Accrual failure in a transplant-conditioning pilot at a single centre does not generalise to a cooperative-group therapeutic trial: the POETIC consortium successfully enrolled 20 patients to a plerixafor chemosensitisation study across multiple sites in the same era. Feasibility is a function of design and network, not of the drug. Seattle Children's Hospital; POETIC consortium 2016
the only completed paediatric therapeutic record the sweep found
registry sweep: no CXCR4-directed trial exists in KMT2A-rearranged or infant leukaemia
the untested population; registry absence is an upper bound because condition strings rarely carry fusion genotypes
the drug behind this graph's CXCR4-directed trial census