Pediatric Cancer Clinical Trials 2026: Childhood Leukemia, Brain Tumors, and Solid Tumors

Pediatric oncology has produced the most dramatic survival improvement in cancer medicine — acute lymphoblastic leukemia that killed roughly 90% of affected children in the 1960s now has 5-year survival rates above 90% in high-resource settings. That was achieved almost entirely through clinical trial participation and systematic comparison of treatment approaches in cooperative group studies. The field has been its own best argument for clinical research. What makes the current moment genuinely different is that DIPG — diffuse intrinsic pontine glioma, historically one of the most hopeless diagnoses in all of pediatric medicine — now has drugs showing actual tumor regression. That hasn't happened before.

The Children's Oncology Group: How It Works

COG is the infrastructure through which most pediatric oncology progress happens in the US, Canada, Europe, and Australia. Over 200 member institutions participate, and when a child is diagnosed at a COG center, their oncologist can offer enrollment in active COG protocols. This is important: many COG frontline protocols aren't "experimental" in the sense people usually mean — they represent the current best standard of care for newly diagnosed patients, refined through decades of systematic trial data. Participating in a COG study for newly diagnosed ALL, for example, is participating in the process that has driven survival from 10% to over 90%.

• Finding a COG center: childrensoncologygroup.org lists all member institutions. If your local hospital is not a COG member, requesting a second opinion at a major children's cancer center — St. Jude, CHOP, Children's Hospital Los Angeles, Dana-Farber/Boston Children's — is the most important single step a family can take early in diagnosis.
• Active COG studies in 2026 span ALL, AML, brain tumors, neuroblastoma, Wilms tumor, rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, and lymphoma.
• Protocol types: Frontline treatment protocols (newly diagnosed), salvage protocols (relapsed/refractory), biology studies (no treatment change, contributes tumor biospecimens), and long-term follow-up studies tracking late effects of successful treatment.

CAR-T Cell Therapy: Beyond the First Generation

Tisagenlecleucel (Kymriah) was the first FDA-approved CAR-T therapy — authorized in 2017 for children and young adults up to age 25 with relapsed/refractory B-cell ALL. The pivotal ELIANA trial (NCT02435849) showed an 81% overall remission rate in a population where standard options were exhausted. That's a remarkable number for a disease that kills most patients who relapse twice. By 2026, the landscape has expanded considerably beyond CD19-directed first-generation products.

• CD22-targeted CAR-T: A meaningful fraction of B-ALL patients who respond to CD19 CAR-T relapse because the leukemia loses CD19 expression — antigen escape. CD22-directed products and dual CD19/CD22 targeting constructs are in Phase 1/2 trials specifically designed to address this resistance mechanism.
• T-cell ALL: CAR-T for T-lineage leukemia faces the fratricide problem — T-cells killing each other because the target antigen is expressed on the therapeutic cells themselves. Allogeneic CAR-T products from healthy donors and gene-edited approaches are in early trials working around this barrier.
• Comparator CAR-T trials: With multiple approved and investigational products now available, trials comparing different CAR-T constructs head-to-head are beginning — the kind of data that will eventually guide clinical decision-making about which product to use for which patient.

DIPG and Pediatric Brain Tumors: A Genuine Inflection Point

Diffuse Intrinsic Pontine Glioma — now classified as a subtype of Diffuse Midline Glioma with H3K27M mutation — has had essentially no treatment options for decades. Radiation provides temporary symptom relief. Median survival has been 9–11 months. That has been the honest answer for fifty years. The H3K27M mutation discovery changed the scientific framing by providing a specific molecular target, and the drugs that followed are producing results that weren't seen before.

• ONC201 (dordaviprone): A DRD2/DRD3 antagonist and ClpP agonist with striking activity in H3K27M-mutant DMG. The drug received FDA accelerated approval in April 2024 for recurrent H3K27M+ DMG based on response data. The pivotal ACTION trial (NCT05580562) is now testing it in the frontline setting following radiation — the first time a drug has been advanced to a frontline Phase 3 in DIPG. This is what a genuine breakthrough in a previously untreatable cancer looks like.
• GD2-directed CAR-T for DIPG: The MSKCC Phase 1 trial (NCT04196413) delivers CAR-T cells directly into the tumor via intracranial catheter, bypassing the blood-brain barrier. Preliminary results have shown tumor regression in some patients with extended survival compared to historical controls — early data, small numbers, but unprecedented for this disease.
• Convection-enhanced delivery (CED): Direct infusion of therapeutic agents into the brainstem via stereotactically placed catheter, used to deliver immunotoxins and small molecules. The approach bypasses the blood-brain barrier mechanically. Multiple CED trials are active at specialist centers.
• Medulloblastoma molecular stratification: COG ACNS1422 and successor studies now risk-stratify treatment based on molecular subgroup — WNT, SHH, Group 3, Group 4 — with trials reducing treatment intensity in low-risk groups to decrease long-term toxicity and intensifying in high-risk groups. This is precision oncology applied to a tumor type that wasn't amenable to it until recently.

NTRK Inhibitors: A Tumor-Agnostic Approval That Matters Most in Pediatrics

NTRK gene fusions involving NTRK1, NTRK2, or NTRK3 occur across many tumor types but are particularly enriched in certain pediatric cancers. Larotrectinib (Vitrakvi) and entrectinib (Rozlytrek) received FDA approval in 2018 and 2019 respectively — the first approvals based on a molecular marker rather than a specific tumor type or histology. Response rates in TRK fusion-positive tumors are approximately 75–80%, with durable responses in many patients. These drugs work regardless of where the cancer started, as long as the tumor harbors an NTRK fusion.

• Tumor types with high NTRK fusion prevalence: Infantile fibrosarcoma (~90% harbor ETV6-NTRK3), secretory carcinomas, congenital mesoblastic nephroma, and certain pontine glioma subtypes. These are tumors where the first question after diagnosis should be: has NTRK fusion status been tested?
• Next-generation TRK inhibitors: Selitrectinib (LOXO-195) and repotrectinib target the resistance mutations that emerge after first-generation TRK inhibitor progression. Pediatric expansion cohorts are enrolling. The goal is to extend the duration of benefit by sequencing inhibitors as resistance emerges.
• Testing caveat: Standard DNA-based next-generation sequencing panels miss NTRK fusions at high rates. RNA-based fusion testing is the preferred approach. If your institution is not routinely doing RNA-based fusion testing, this is a specific conversation to have with the pathologist or oncologist.

Neuroblastoma, Ewing, and the Tumors That Still Lack Progress

High-risk neuroblastoma is one of the most challenging solid tumors in pediatric oncology despite multimodal treatment — high-dose chemotherapy, autologous stem cell transplant, surgery, dinutuximab immunotherapy, and isotretinoin maintenance. Long-term survival for high-risk disease is approximately 50%. Active 2026 trials include:

• GD2-targeted approaches: Naxitamab (Danyelza), an anti-GD2 antibody, was approved for relapsed/refractory high-risk neuroblastoma in 2020. Combination trials with DFMO (difluoromethylornithine) as maintenance therapy after dinutuximab are testing whether polyamine synthesis inhibition extends remission.
• Ewing sarcoma: There is no approved second-line treatment for relapsed Ewing — this is a gap that has persisted for decades. Phase 2 trials evaluating lurbinectedin (which inhibits oncogenic transcription), cabozantinib, and combination immunotherapy approaches are active. Response rates in the relapsed setting remain poor, but the molecular biology of EWSR1 fusion proteins is now better understood and is generating rational drug targets.
• Osteosarcoma: The standard chemotherapy regimen — MAP (methotrexate, doxorubicin, cisplatin) — has been essentially unchanged since the 1970s. AOST trials are testing cabozantinib plus nivolumab and other novel combinations, but osteosarcoma remains one of the most frustratingly slow areas for new approvals in all of pediatric oncology.

How Families Navigate Pediatric Cancer Trial Access

• Get to a COG center from diagnosis. Don't wait until relapse. Frontline COG protocols are available to newly diagnosed patients and often represent the best available care, not experimental last resorts.
• Request comprehensive genomic profiling at diagnosis. RNA-based fusion testing plus DNA sequencing of the tumor identifies NTRK fusions, BRAF V600E, ALK, ROS1, and other targetable alterations. This is the molecular roadmap for trial eligibility — and it needs to be done early, before the window for enrollment in frontline trials closes.
• Alex's Lemonade Stand Foundation maintains a pediatric-specific clinical trial finder and patient navigation services that are more useful than general ClinicalTrials.gov searches for families navigating pediatric oncology.
• The Pediatric Brain Tumor Atlas (PBTA) and St. Jude Cloud data sharing initiatives help match patients with rare brain tumor variants to trials by identifying molecular alterations in tumor specimens contributed by participating institutions.