COG AINV18P1 (NCT03792256) — palbociclib is deliverable in children with relapsed ALL, at 50 mg/m² for 21 days
also called AINV18P1 · NCT03792256 · COG palbociclib ALL
A Children's Oncology Group study added the cell-cycle drug palbociclib to standard re-treatment chemotherapy in twelve children and young adults whose leukemia had come back. It was tolerated, it produced a dose that can be used in children, and five of them went into complete remission.
The same thing, for a scientist
Phase 1 of palbociclib with standard four-drug re-induction in 12 heavily pretreated children and young adults with relapsed/refractory B- and T-lymphoblastic leukemia and lymphoma. Palbociclib 50 mg/m²/dose orally once daily for 21 consecutive days, given first as a single agent on days 1-3 and then with chemotherapy, in a two-part design of dose determination followed by a pharmacokinetic expansion. One dose-limiting haematologic toxicity at the starting dose and none thereafter; grade 3/4 non-haematologic toxicity comparable to the chemotherapy platform alone; **recommended phase 2 dose 50 mg/m²/day for 21 days**; five complete responses (2 of 4 T-ALL, 3 of 7 B-ALL); similar pharmacokinetics for liquid and capsule formulations [E1]. This entry records what the trial does establish — feasibility, dose and formulation in children — and is explicit that it establishes nothing about KMT2A-rearranged disease.
What it establishes
The barrier to using an adult oncology drug in children is usually not biology but dose, formulation and tolerability in combination. This trial cleared all three: a defined recommended phase 2 dose, pharmacokinetic equivalence of a liquid formulation (which matters enormously for infants and small children), and a toxicity profile that did not exceed the chemotherapy backbone apart from one haematologic dose-limiting toxicity 1.
For this project that is the useful content. If a CDK4/6 inhibitor were ever to be tested in KMT2A-rearranged infant leukemia, this trial is the reason it could be, and the liquid formulation result is the specific fact that makes an infant study conceivable at all.
What it does not establish, stated plainly
- Not efficacy. n=12, phase 1, no control, and palbociclib was given with four-drug re-induction. Five complete responses in heavily pretreated relapsed ALL is a reasonable outcome for re-induction chemotherapy on its own, and nothing in the design attributes any of them to the added agent.
- Not fusion-selected. The abstract reports no KMT2A-rearranged subgroup. Whether any enrolled patient carried the rearrangement is unknown from what was read.
- Not infants. The population is children and young adults with relapsed disease.
The temptation this entry exists to resist is chaining 'CCND3 ranks 4 in a scan' to 'CDK4/6 inhibition has pediatric responses' and concluding something about KMT2A-rearranged infant leukemia. Those are three separate populations and the chain does not close.
The rest of the pediatric record
Two further pediatric palbociclib ALL studies are on the registry and neither delivered: NCT03515200 (St. Jude, phase 1 with chemotherapy) is recorded as terminated with 12 participants, and NCT04996160 (Stanford, RELPALL2) as completed with 2 2. A ribociclib trial in children and young adults with relapsed ALL, NCT03740334 (Dana-Farber, ribociclib with everolimus and dexamethasone, 45 enrolled), is recorded as active but not recruiting.
The pattern is a class that can be given to children but has struggled to accrue in single-centre relapsed-ALL studies. The cooperative-group route worked where the single-centre route did not, which is a practical lesson for any future design.
| nct | NCT03792256 |
|---|---|
| phase | Phase 1 |
| status | completed |
| sponsor | Children's Oncology Group |
| n | 12 |
| population | children and young adults with relapsed/refractory B- and T-lymphoblastic leukemia and lymphoma; not selected for fusion status |
| readout | maximum tolerated dose / recommended phase 2 dose, toxicity, pharmacokinetics; responses reported descriptively |
| result | RP2D 50 mg/m2/day x 21 days; 1 haematologic DLT at the starting dose; grade 3/4 non-haematologic toxicity comparable to the chemotherapy platform; 5 complete responses among 12; liquid and capsule formulations pharmacokinetically similar |
| relevance to kmt2a r | none directly; establishes pediatric dose, tolerability and a liquid formulation, which are the practical prerequisites for any future fusion-selected or infant study |
| entered graph via | followed from the scan hit gene-ccnd3 |
arms
[ "palbociclib 50 mg/m2/day orally x 21 days, days 1-3 single agent then with four-drug re-induction (cytarabine, methotrexate, doxorubicin, vincristine, pegaspargase, corticosteroid, intrathecal therapy per the registry intervention list)" ]
related trials
[ "NCT03515200", "NCT04996160", "NCT03740334", "NCT02310243" ]
- A phase 1 with 5 complete responses in 12 patients is exactly the kind of result that gets over-read. There is no control arm, the backbone is a four-drug re-induction that produces remissions on its own, and no response here can be attributed to palbociclib.
- The one dose-limiting toxicity was haematologic, in a disease whose central problem is marrow failure. In infants, whose marrow reserve and infection risk are worse, that is the toxicity that would set the ceiling.
- Did any AINV18P1 patient carry a KMT2A rearrangement, and if so what happened? Twelve patients is small enough that a single case report would be informative, and the COG banks the data.
- Does the liquid formulation reach infant-appropriate dosing? This is the practical gate on whether a CDK4/6 inhibitor could ever be given in infant KMT2A-rearranged ALL, and the pharmacokinetic cohort here is the closest existing data.
- What were the haematologic recovery kinetics? Adding a myelosuppressive agent to re-induction in infants is the toxicity that would decide feasibility, and the abstract does not give it.
- E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper
In the Children's Oncology Group AINV18P1 phase 1 trial, palbociclib 50 mg/m2/dose orally once daily for 21 consecutive days — first as a single agent on days 1-3 and then combined with standard four-drug re-induction chemotherapy — was evaluated in 12 heavily pretreated children and young adults with relapsed/refractory B- and T-lymphoblastic leukemia and lymphoma; one dose-limiting haematologic toxicity occurred at the starting dose with no additional dose-limiting toxicities in the dose determination or pharmacokinetic expansion cohorts; overall rates of grade 3/4 non-haematologic toxicity were comparable to the chemotherapy platform alone; five complete responses were observed (2 of 4 patients with T-ALL and 3 of 7 with B-ALL); pharmacokinetic profiles were similar for liquid and capsule formulations; and the recommended phase 2 dose was 50 mg/m2/day for 21 days.
Palbociclib in combination with chemotherapy in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia and lymphoma: A Children's Oncology Group study (AINV18P1) · Raetz EA, Teachey DT, Minard C, Liu X, Norris RE, Denic KZ, Reid J, Evensen NA, Gore L, Fox E, Loh ML, Weigel BJ, Carroll WL · Pediatric Blood & Cancer 70:e30609 2023What this evidence cannot show
Read as abstract only. Phase 1, n=12, no control arm, no reported selection or subgroup analysis by fusion status, no infants. Responses occurred within a four-drug re-induction combination and cannot be attributed to palbociclib. The trial's stated rationale is cyclin D in ALL generally, not KMT2A rearrangement.
Evidence that argues against this (1)
- The one trial that was selected for MLL rearrangement, and was single-agent, and therefore could have attributed an effect, completed in 2019 and posted no results. University of Ulm; Pfizer; National Center for Tumor Diseases et al. 2015
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registry
A St. Jude phase 1 study of palbociclib with chemotherapy in pediatric relapsed/refractory ALL (NCT03515200) is recorded as terminated with 12 participants, and a Stanford phase 1 study of the same combination (NCT04996160, RELPALL2) is recorded as completed with 2 participants; a Dana-Farber phase 1 of ribociclib with everolimus and dexamethasone in children and young adults with relapsed ALL (NCT03740334) is recorded as active, not recruiting, with 45 enrolled.
A Phase I Study of Palbociclib in Combination With Chemotherapy in Pediatric Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia · St. Jude Children's Research Hospital · ClinicalTrials.gov 2018What this evidence cannot show
Registry summary fields read via the ClinicalTrials.gov API on 2026-09-18. Reasons for termination are not given in the fields read, and none of these studies was selected for KMT2A rearrangement. Enrolment figures in a registry summary are the recorded value, which for terminated studies may be actual and for others may be target.
Evidence that argues against this (1)
- Low accrual in single-centre relapsed pediatric ALL studies is the norm rather than a signal about the drug, and the cooperative-group version of essentially the same study completed its dose finding without difficulty. Raetz EA et al. 2023
establishes the pediatric dose, liquid formulation and tolerability of the class, unselected for fusion
Children's Oncology Group phase 1 (AINV18P1)