Abstract
Background: Cyclin D has been shown to play an essential role in acute lymphoblastic leukemia (ALL) initiation and progression, providing rationale for targeting the CDK4/6-cyclin D complex that regulates cell cycle progression. Procedure: The Children's Oncology Group AINV18P1 phase 1 trial evaluated the CDK4/6 inhibitor, palbociclib, in combination with standard four-drug re-induction chemotherapy in children and young adults with relapsed/refractory B- and T-cell lymphoblastic leukemia (ALL) and lymphoma. Palbociclib (50 mg/m2/dose) was administered orally once daily for 21 consecutive days, first as a single agent (Days 1–3) and subsequently combined with re-induction chemotherapy. This two-part study was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D), followed by an expansion pharmacokinetic cohort. Results: Twelve heavily pretreated patients enrolled, all of whom were evaluable for toxicity. One dose-limiting hematologic toxicity (DLT) occurred at the starting dose of 50 mg/m2/dose orally for 21 days. No additional DLTs were observed in the dose determination or pharmacokinetic expansion cohorts, and overall rates of grade 3/4 nonhematologic toxicities were comparable to those observed with the chemotherapy platform alone. Five complete responses were observed, two among four patients with T-ALL and three among seven patients with B-ALL. Pharmacokinetic studies showed similar profiles with both liquid and capsule formulations of palbociclib. Conclusions: Palbociclib in combination with re-induction chemotherapy was well tolerated with a RP2D of 50 mg/m2/day for 21 days. Complete responses were observed among heavily pretreated patients.
Original language | English (US) |
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Article number | e30609 |
Journal | Pediatric Blood and Cancer |
Volume | 70 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2023 |
Keywords
- acute lymphoblastic leukemia
- palbociclib
- pediatric
- relapse
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Hematology
- Oncology