Ignite Creation Date:
2024-05-06 @ 7:37 AM
Last Modification Date:
2024-10-26 @ 11:50 AM
Study NCT ID:
NCT02564536
Status:
WITHDRAWN
Last Update Posted:
2017-05-08
First Post:
2015-09-29
Brief Title:
Pacritinib in Combination With Low Dose Decitabine in Intermediate-High Risk Myelofibrosis or Myeloproliferative Neoplasm MPNMyelodysplastic Syndrome MDS
Sponsor:
Washington University School of Medicine
Organization:
Washington University School of Medicine
Study Overview
Official Title:
A Pilot Study of Pacritinib in Combination With Low Dose Decitabine in Patients With Intermediate-High Risk Myelofibrosis or MPNMDS Syndromes
Status:
WITHDRAWN
Status Verified Date:
2017-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Lack of funding following full FDA clinical hold
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
For the first 28 day cycle all patients will be treated with single agent pacritinib at 200 mg twice daily The investigators chose this starting dose based on the previous three phase I studies of pacritinib as a single agent which showed that the maximum tolerated dose MTD to be 500 mg and subsequently the dose of 400 mg daily was recommended for the phase II studies
Recently the results of the phase III PERSIST-1 trial comparing pacritinib to best available therapy BAT in patients with MF was reported at the 2015 American Society of Clinical Oncology ASCO annual meeting Pacritinib was found to be significantly more effective than BAT at reducing spleen volume at 24 weeks of therapy and improving constitutional symptoms
Low dose decitabine has demonstrated depletion of DNMT1 in normal hematopoietic stem cells HSC without cytotoxicity and subcutaneous SC instead of intravenous IV administration may avoid high peak levels that can cause apoptosis Furthermore the low toxicity associated with low dose decitabine would allow for more frequent 1 to 3 times weekly administration of the drug which would catch more cells in S-phase via greater exposure time Based on these findings a starting dose of decitabine 5 mgm2 SC twice weekly should be well tolerated and effective in patients with MF and MPNMDS syndromes when combined with pacritinib 400 mg daily
Recently the results of the phase III PERSIST-1 trial comparing pacritinib to best available therapy BAT in patients with MF was reported at the 2015 American Society of Clinical Oncology ASCO annual meeting Pacritinib was found to be significantly more effective than BAT at reducing spleen volume at 24 weeks of therapy and improving constitutional symptoms
Low dose decitabine has demonstrated depletion of DNMT1 in normal hematopoietic stem cells HSC without cytotoxicity and subcutaneous SC instead of intravenous IV administration may avoid high peak levels that can cause apoptosis Furthermore the low toxicity associated with low dose decitabine would allow for more frequent 1 to 3 times weekly administration of the drug which would catch more cells in S-phase via greater exposure time Based on these findings a starting dose of decitabine 5 mgm2 SC twice weekly should be well tolerated and effective in patients with MF and MPNMDS syndromes when combined with pacritinib 400 mg daily
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None