In:
Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_2 ( 2020-11-09), p. ii51-ii51
Abstract:
Ruxolitinib is a novel, potent, and selective inhibitor of JAK1 (Janus kinase 1) and JAK2 with modest to marked selectivity against TYK2 (tyrosine kinase 2) and JAK3, respectively. Dysregulation of the JAK/STAT pathway has been associated with several types of cancer and increased proliferation and survival of malignant cells. METHODS Newly diagnosed patients with unmethylated MGMT Glioblastoma or grade III glioma were recruited to Arm I. Every patient received ruxolitinib and 60 Gy radiation for 6 weeks over 6 weeks (2Gy x 30). The dose of Ruxolitinib was administered given the 3 + 3 design. Level 1 or starting dose was 10 mg twice daily, level 2 was 15 mg twice daily, level 3 was 20 mg twice daily and level -1 was 5 mg twice daily. Arm two was started once safe dose was established for Arm 1 for each dose level. Patients with methylated MGMT glioblastoma or grade III glioma were eligible for Arm 2. Every patient received ruxolitinib + radiation x 60 Gy + daily temozolomide at 75 mg/m2 for 6 weeks over 6 weeks. RESULTS 30 patients were randomized to Arm I and 16 to arm II. There was one partial response in the methylated Arm and one partial response in the unmethylated arm. The maximum tolerated dose of Ruxolitinib was 20 mg BID in both methylated and unmethylated arm. There were 14 incidences of Grade 3 toxicity including respiratory distress, seizure, gait disturbance, weakness, thrombocytopenia, cognitive disturbance, urinary retention, and bacterial meningitis. There were 4 incidences of Grade 4 toxicity including seizure, respiratory distress, somnolence and thromboembolic events. CONCLUSION This is an ongoing clinical trial and final results will be presented once the trial is complete. We will perform single cell sequencing on good and poor responders, that data will be presented in the meeting.
Type of Medium:
Online Resource
ISSN:
1522-8517
,
1523-5866
DOI:
10.1093/neuonc/noaa215.207
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2020
detail.hit.zdb_id:
2094060-9
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