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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)
  • +10
  • Elizabeth Raetz,
  • David T. Teachey,
  • Charles Minard,
  • Xiaowei Liu,
  • Robin Norris,
  • Kristina Z. Denic,
  • Joel Reid,
  • Nikki Evensen,
  • Lia Gore,
  • Elizabeth Fox,
  • Mignon Loh,
  • Brenda Weigel,
  • William Carroll
Elizabeth Raetz
NYU Langone Health

Corresponding Author:[email protected]

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David T. Teachey
The Children's Hospital of Philadelphia Center for Childhood Cancer Research
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Charles Minard
Baylor College of Medicine
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Xiaowei Liu
Children's Oncology Group
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Robin Norris
Cincinnati Children's Hospital Medical Center Cancer and Blood Diseases Institute
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Kristina Z. Denic
Mayo Clinic Department of Oncology
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Joel Reid
Mayo Clinic Department of Oncology
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Nikki Evensen
NYU Langone Health
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Lia Gore
UC Health University of Colorado Hospital
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Elizabeth Fox
St Jude Children's Research Hospital Department of Oncology
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Mignon Loh
University of Washington
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Brenda Weigel
University of Minnesota Masonic Cancer Center
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William Carroll
NYU Langone Health
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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 reinduction chemotherapy in children and young adults with relapsed/refractory B- and T-cell lymphoblastic leukemia (ALL) and lymphoma. Palbociclib (50 mg/m 2/dose) was administered orally once daily for 21 consecutive days, first as a single agent (days 1-3) and subsequently combined with reinduction 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 (PK) 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/m 2/dose orally for 21 days. No additional DLTs were observed in the dose determination or PK expansion cohorts and overall rates of grade 3/4 non-hematologic 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 reinduction chemotherapy was well tolerated with a RP2D of 50 mg/m 2/day for 21 days. Complete responses were observed among heavily pretreated patients.
20 Mar 2023Submitted to Pediatric Blood & Cancer
20 Mar 2023Submission Checks Completed
20 Mar 2023Assigned to Editor
27 Mar 2023Review(s) Completed, Editorial Evaluation Pending
28 Mar 2023Reviewer(s) Assigned
17 May 2023Editorial Decision: Revise Minor
11 Jun 20231st Revision Received
11 Jun 2023Assigned to Editor
11 Jun 2023Submission Checks Completed
13 Jun 2023Review(s) Completed, Editorial Evaluation Pending
13 Jun 2023Reviewer(s) Assigned
14 Jul 2023Editorial Decision: Revise Minor
19 Jul 20232nd Revision Received
19 Jul 2023Submission Checks Completed
19 Jul 2023Assigned to Editor
19 Jul 2023Review(s) Completed, Editorial Evaluation Pending
21 Jul 2023Editorial Decision: Accept