Interfant-21 (NCT05327894) — the randomised test of blinatumomab in infant KMT2A-rearranged ALL, open now
also called Interfant-21 · NCT05327894
Interfant-21 is the worldwide trial running right now for babies under one year with KMT2A-rearranged leukemia. It is the experiment that will show whether the striking blinatumomab results were real.
The same thing, for a scientist
Interfant-21 is a phase 3 international protocol (Princess Máxima Center, 124 sites, target enrolment 160, opened 15 December 2022, primary completion September 2027) for infants under 1 year with KMT2A-rearranged ALL or mixed phenotype acute leukemia, with blinatumomab as the investigational intervention. It is the randomised successor to the 30-patient single-arm Interfant-06+blinatumomab study whose 4-year DFS of 83.3% versus 44.0% historical control is currently the field's headline number. Until Interfant-21 reads out, that number rests on a selected historical comparison.
Why this is the most important open trial in the disease
Two prior randomised questions in infant ALL — late intensification in Interfant-99 and myeloid-style consolidation in Interfant-06 — were both negative, across more than 1,100 infants. Interfant-21 is the first randomised protocol in this population built around a mechanism that is not cytotoxic dose intensity.
Status as of 2026-09-18: RECRUITING. Phase 3. Target enrolment 160. 124 locations. Primary completion September 2027 1.
Pediatric-eligible: yes, by definition — the population is infants under one year, the narrowest and hardest-to-enrol group in oncology. 160 patients in a disease with roughly this incidence is a multi-year international undertaking, which is why the trial spans 124 sites.
What it cannot answer
Interfant-21 tests blinatumomab on the Interfant-06 backbone. It does not test menin inhibition, and it does not test the combination. That is a structural gap in the field's plan: by the time Interfant-21 reports in 2027-2028, revumenib and ziftomenib will have been approved for several years, and the frontline infant question 'menin inhibitor, T-cell engager, or both' will still be unanswered by any randomised trial.
The partial exceptions are NCT06317662 (NCI/COG, blinatumomab + chemotherapy for newly diagnosed infants, with KMT2A-rearranged patients randomised to the addition of venetoclax; recruiting, n=153, 115 sites) and TINI 2, NCT05848687 (St. Jude/Stanford, phase 1/2, n=90, recruiting, which includes both blinatumomab and ziftomenib in a total-therapy design) 2. Between them, the frontline infant landscape in 2026 is testing blinatumomab±venetoclax and blinatumomab+ziftomenib — but no trial anywhere randomises a menin inhibitor in frontline infant ALL.
| nct | NCT05327894 |
|---|---|
| phase | Phase 3 |
| status | RECRUITING as of 2026-09-18 |
| open now | true |
| pediatric eligible | true |
| n | 160 |
| locations count | 124 |
| sponsor | Princess Máxima Center for Pediatric Oncology |
| start date | 2022-12-15 |
| primary completion date | 2027-09 |
| population | Infants <1 year with KMT2A-rearranged ALL or mixed phenotype acute leukemia |
| readout | Pending; will determine whether the single-arm blinatumomab benefit survives randomisation |
interventions
[ "blinatumomab", "Interfant-06-derived chemotherapy backbone" ]
- Lineage switch: randomising blinatumomab into frontline infant therapy applies CD19 pressure to the genotype most prone to myeloid escape, and a switched relapse is harder to treat than the original disease.
- Antigen exhaustion of the pipeline: using CD19 upfront removes CD19 CAR-T as a salvage option for some children, and no equally effective second antigen is established in infants.
- Delivery: continuous infusion in infants across 124 international sites is an operational burden that may itself limit protocol adherence and generate per-site outcome heterogeneity.
- Late effects: B-cell aplasia and hypogammaglobulinaemia imposed during the first year of life overlap the primary immunisation schedule; long-term vaccine responsiveness in these children is unmeasured.
- Will the effect survive randomisation? A 4-year DFS gap of 83.3% versus 44.0% would be the largest treatment effect ever seen in this disease; effects that large against historical controls usually shrink.
- Should Interfant-21 have included a menin-inhibitor arm? By its readout date, menin inhibitors will have been approved for years with no frontline infant randomised data, and the opportunity to answer both questions in one protocol will have passed.
- What happens to infants who relapse on Interfant-21? If lineage switch to AML is the dominant post-blinatumomab failure mode, the trial must be powered to detect it as a distinct event class rather than as generic relapse.
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.trial_registry
Interfant-21 (NCT05327894) is a recruiting phase 3 international protocol sponsored by the Princess Máxima Center for infants under one year with KMT2A-rearranged ALL or mixed phenotype acute leukemia, with blinatumomab as intervention, target enrolment 160 across 124 locations, started 15 December 2022 with primary completion September 2027.
Interfant-21 International Collaborative Treatment Protocol for Infants Under One Year With KMT2A-rearranged Acute Lymphoblastic Leukemia or Mixed Phenotype Acute Leukemia · Princess Maxima Center for Pediatric Oncology · ClinicalTrials.gov 2026What this evidence cannot show
Registry records are sponsor-maintained and update irregularly; recruitment status and site counts can lag reality by months. The registry entry lists blinatumomab twice as an intervention without making the randomised comparison explicit in the summary fields, so the exact randomisation structure should be confirmed from the protocol before being described in detail.
Evidence that argues against this (1)
- The result Interfant-21 is testing was generated in 30 infants in a single-arm add-on study whose comparator was the historical Interfant-06 cohort, so the effect size being carried into the randomised trial may be inflated by patient selection and by supportive-care era effects. The specific structural risk for a CD19-directed agent in this genotype is escape by lineage switch: KMT2A-rearranged B-ALL has been shown to relapse after CD19-directed therapy as clonally related CD19-negative acute myeloid leukaemia, an event a blinatumomab EFS endpoint counts as a failure but which no amount of blinatumomab intensity would prevent. Gardner R et al. 2016
- E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.trial_registry
Two other frontline infant leukemia trials are recruiting as of September 2026: NCT06317662 (NCI, phase 2, n=153, blinatumomab plus chemotherapy with randomisation of KMT2A-rearranged patients to addition of venetoclax, 115 sites) and NCT05848687 (TINI 2, phase 1/2, n=90, including blinatumomab and ziftomenib, 24 sites).
A Phase 2 Study of Blinatumomab in Combination With Chemotherapy for Infants With Newly Diagnosed Acute Lymphoblastic Leukemia With Randomization of KMT2A-Rearranged Patients to Addition of Venetoclax · National Cancer Institute (NCI) · ClinicalTrials.gov 2026What this evidence cannot show
Registry data only. TINI 2 is NCT05848687. Neither trial has reported results, and NCT06317662 opened only in June 2025.
Evidence that argues against this (1)
- Neither of these recruiting trials is a randomised test of a menin inhibitor in frontline infant ALL, so the pair cannot be cited as evidence that the question is being answered. Raw ClinicalTrials.gov v2 API, retrieved 2026-09-19: in NCT06317662 the randomisation is of VENETOCLAX, not of a menin inhibitor, and its primary outcomes are dose-limiting toxicity incidence in the safety and expansion phases plus MRD-negative remission rate at the end of induction, with primary completion 2028-12-31. TINI 2 (NCT05848687) is a Stanford-sponsored phase 1/2 with estimated n=90, a maximum age of 1 year, a SINGLE primary outcome of 'Minimal Residual Disease' with a time frame of 5 years and 2 months, primary completion 2028-12 and study completion 2033-12; ziftomenib is one of nine listed interventions in a total-therapy backbone and is not separately randomised, so its contribution will not be estimable from this design. Stanford University 2023
full dosing from 6 months reverted after excess infectious deaths in induction
the contemporaneous cohort a concurrent external control would draw on
- tests →Blinatumomab in infant KMT2A-rearranged ALL — the largest single outcome gain in thirty years
the randomised test of adding blinatumomab up front
infant randomised trial context
the randomised successor adding blinatumomab to this backbone
the trial now running that could close this reporting gap if it pre-specifies partner
- ← related toBlinatumomab in infant KMT2A-rearranged ALL — the largest single outcome gain in thirty years
Counter-evidence (Vieira Martins 2026, PMID 41505662): the 30-infant blinatumomab benefit rests on a historical Interfant-06-SELECTED control (4-year DFS 83.3% vs 44.0%, OS 93.3% vs 60.2%) and IVIg was given to 19/30; the authors state the frontline benefit awaits confirmation in ongoing randomised trials
Counter-evidence (ClinicalTrials.gov v2 API, NCT05848687, retrieved 2026-09-19): TINI 2 already gives the menin inhibitor ziftomenib to infants frontline (max age 1 year, n=90 estimated) -- the absence is of a RANDOMISATION, not of frontline infant exposure; and NCT07211958 opens at 12 years, so the 3,091-patient phase 3 total is not exclusively adult
- tests →Blinatumomab in infant KMT2A-rearranged ALL — the largest single outcome gain in thirty years
the randomised test of the single-arm blinatumomab result
- related to →Interfant-06 — 651 infants, and the definitive answer that myeloid-style consolidation does not help
successor protocol; uses the Interfant-06 backbone and risk model
listed as recruiting, phase 3, n=160, 124 sites