Phase I and pharmacokinetic (PK) study of lenalidomide (LEN) in pediatric patients with relapsed/refractory solid tumors or myelodysplastic syndrome (MDS): A Children's Oncology Group Phase I Consortium study

Abstract

10023 Background: LEN, which has immunomodulatory, antiangiogenic, and antiproliferative effects, is indicated for the treatment of adults with MDS and multiple myeloma. We report the final results of a phase 1 and PK study of LEN in children with recurrent or refractory solid tumors (ST) or MDS. Methods: LEN was administered by mouth once daily for 21 of 28 days. Cohorts of 3 to 12 children with ST were enrolled at 15, 25, 40, 55 and 70 mg/m2/d dose levels. Children with MDS received a fixed dose of 5 mg/m2/d. PK and correlative biology studies were performed in cycle 1. Results: 49 patients (23 female), median age 16 years (range, 1–21) were enrolled and received a median of 1 cycle (range 1–11). 39/46 ST patients and 3/3 MDS patients were fully evaluable for toxicity. 0/3 patients with MDS had DLT. At 15 mg/m2/d, 1/6 ST patients developed DLT (Gr 3 hypercalcemia). At 25 mg/m2/d 1 patient had a cerebrovascular ischemic event of uncertain relationship to LEN; future subjects were screened for thromboembolic risk factors prior to enrollment. At 40 mg/m2/d 3/12 patients developed DLTs (Gr 3 hypophosphatemia/hypokalemia; Gr 4 neutropenia delaying the start of the next cycle for > 7 days; Gr 3 somnolence); at 55 mg/m2/d 1/6 patients developed DLT (Gr 3 urticaria). At 70 mg/m2/d 0/6 patients had DLT. No further dose escalation was attempted. No objective responses were observed. LEN enhanced IL-2 and IL-15 concentrations; NK expansion and activation; and NK and LAK cytotoxicity (Ayello, ASH, 2008). The median apparent LEN clearance and half-life were 135 ± 45 ml/min/m2 and 2.3 ± 1.1 hr. Conclusions: LEN is well tolerated at doses up to 70 mg/m2/d x 21d of 28 days in children with recurrent or refractory ST. Enhancement of immune function is significant. PK parameters in children are similar to those in adults. No significant financial relationships to disclose.