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Phase II Randomized Trial of Lenalidomide in Children With Pilocytic Astrocytomas and Optic Pathway Gliomas: A Report
Katherine E Warren1, Gilbert Vezina2, Mark Krailo3
1Dana Farber Cancer Institute/Boston Children's Hospital, Boston, MA.
Purpose:
Children with low-grade glioma often require long-term therapy and suffer from treatment morbidity. Although targeted agents are promising, tumor targets often encompass normal developmental pathways and long-term effects of inhibition are unknown. Lenalidomide is an immunomodulatory agent with wide-ranging properties. Phase I studies indicated greater tolerability of lenalidomide in children compared with adults and a potential dose-response effect.
Patients And Methods:
We performed a phase II trial of lenalidomide in children with pilocytic astrocytomas and optic pathway gliomas who failed initial therapy. Primary objectives included determination of objective response rate of children randomly assigned to regimen A, low-dose (20 mg/m2/dose), or regimen B, high-dose (115 mg/m2/dose) lenalidomide, and assessment for early progression. Secondary objectives included estimation of event-free survival, overall survival, incidence of toxic events, and assessment of plasma lenalidomide concentrations. Lenalidomide was administered once daily × 21 days of each 28-day cycle for each regimen.
Results:
Seventy-four eligible patients were enrolled (n = 37, each arm). The predefined activity level of interest was achieved for both arms. Four objective responses were observed in each arm, and the number of early progressors was low. Eighteen patients completed 26 cycles of therapy (regimen A, n = 12; regimen B, n = 6). The median number of cycles was 14 (range, 2-26) for regimen A and 11 for regimen B (range, 1-26). Of 74 eligible patients who received study drug, 30 required dose reduction for toxicity (regimen A, n = 6; regimen B, n = 24) and 16 discontinued because of toxicity (regimen A, n = 2; regimen B, n = 14).
Conclusion:
Lenalidomide demonstrates a sufficient level of activity in children with low-grade glioma to warrant further exploration. Low-dose (20 mg/m2/dose administered once daily × 21 days of each 28-day cycle) lenalidomide appears to have better tolerability with comparable activity.
Insights
Lenalidomide shows promise for treating pediatric low-grade gliomas. The low-dose regimen (20 mg/m² daily) offers better tolerability with similar effectiveness compared to higher doses.
Area of Science:
- Pediatric Oncology
- Neuro-oncology
Background:
- Low-grade gliomas in children necessitate long-term treatment with significant morbidity.
- Targeted therapies face challenges due to effects on normal developmental pathways.
- Lenalidomide, an immunomodulatory agent, shows potential tolerability and dose-response in pediatric studies.
Purpose of the Study:
- To evaluate the efficacy and safety of lenalidomide in children with pilocytic astrocytomas and optic pathway gliomas.
- To compare a low-dose (20 mg/m²) regimen with a high-dose (115 mg/m²) regimen of lenalidomide.
- To assess objective response rates, progression, survival, and toxicity.
Main Methods:
- A Phase II trial was conducted with 74 pediatric patients.
- Patients were randomized to receive lenalidomide at 20 mg/m² (Regimen A) or 115 mg/m² (Regimen B) daily for 21 days of each 28-day cycle.
- Primary endpoints included objective response rate and early progression; secondary endpoints included survival and toxicity.
Main Results:
- Both regimens showed activity, with four objective responses in each arm and a low number of early progressors.
- Eighteen patients completed 26 cycles; median cycles were 14 (Regimen A) and 11 (Regimen B).
- Dose reductions were required for 30 patients (6 in A, 24 in B), and 16 discontinued due to toxicity (2 in A, 14 in B).
Conclusions:
- Lenalidomide demonstrates sufficient activity in pediatric low-grade gliomas for further investigation.
- The low-dose lenalidomide regimen (20 mg/m²) shows comparable activity with improved tolerability.
- Further research is warranted to optimize lenalidomide treatment for pediatric glioma patients.
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