Ignite Creation Date:
2024-05-06 @ 2:46 AM
Last Modification Date:
2024-10-26 @ 11:23 AM
Study NCT ID:
NCT02129101
Status:
COMPLETED
Last Update Posted:
2019-10-30
First Post:
2014-04-30
Brief Title:
Azacitidine and Sonidegib or Decitabine in Treating Patients With Myeloid Malignancies
Sponsor:
Mayo Clinic
Organization:
Mayo Clinic
Study Overview
Official Title:
Phase IIb Study of Azacitidine or Decitabine With Hedgehog Pathway Inhibition in Myeloid Malignancies
Status:
COMPLETED
Status Verified Date:
2019-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase IIb trial studies the side effects and best dose of azacitidine and sonidegib or decitabine and so see how well they work in treating patients with myeloid malignancies The hedgehog Hh signaling pathway plays an important role in cellular growth differentiation and repair Inappropriate activation of Hh pathway signaling and uncontrolled cellular proliferation may be associated with mutations in the Hh-ligand cell surface receptor Smo Sonidegib binds to the Hh cell surface receptor Smo which may result in the suppression of the Hh signaling pathway and the inhibition of cancer cells Azacitidine and decitabine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth Giving azacitidine together with sonidegib or decitabine may be a safe and successful treatment for patients with myeloid malignancies
Detailed Description:
PRIMARY OBJECTIVES
I To estimate the maximally tolerated dose MTD of LDE225 sonidegib days 1-28 in combination with azacitidine overall LDE225 days 1-7 in combination with azacitidine overall and LDE225 days 1-28 in combination with decitabine overall Phase I II To estimate the efficacy of LDE225 days 1-28 in combination with azacitidine in the following subgroups untreated acute myeloid leukemia AMLchronic myelomonocytic leukemia CMMLmyelodysplastic syndrome MDSmyeloproliferative neoplasm MPN overlap relapsedrefractory AMLCMMLMDSMPN overlap and myelofibrosis MF only Phase Ib
SECONDARY OBJECTIVES
I To estimate the duration of response time to progression overall survival and time to AML or death for MDS subjects of LDE225 days 1-28 in combination with azacitidine overall and by cohort Phase I1b
TERTIARY OBJECTIVES
I To conduct correlative studies to measure HH pathway activation and inhibition and explore biomarkers of response
II To evaluate quality of life QOL and patient-reported symptoms using the Myeloproliferative Neoplasm Symptom Assessment Form MPN-SAF and European Organization for Research and Treatment of Cancer EORTC Quality of Life Questionnaire QLQ-Core C30 in subjects treated with LDE225 in combination with azacitidine or decitabine
OUTLINE This is a dose-escalation study of erismodegib
Patients receive azacitidine subcutaneously SC or intravenously IV on days 1-7 sonidegib orally PO once daily QD on days 1-28 or 1-7 or decitabine IV on days 1-5 Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
NOTE Sonidegib PO QD is given on days 1-7 if in combination with azacitidine or on days 1-28 is given if in combination with decitabine
After completion of study treatment patients are followed up every 3 months until progressive disease and then every 6 months for 2 years
I To estimate the maximally tolerated dose MTD of LDE225 sonidegib days 1-28 in combination with azacitidine overall LDE225 days 1-7 in combination with azacitidine overall and LDE225 days 1-28 in combination with decitabine overall Phase I II To estimate the efficacy of LDE225 days 1-28 in combination with azacitidine in the following subgroups untreated acute myeloid leukemia AMLchronic myelomonocytic leukemia CMMLmyelodysplastic syndrome MDSmyeloproliferative neoplasm MPN overlap relapsedrefractory AMLCMMLMDSMPN overlap and myelofibrosis MF only Phase Ib
SECONDARY OBJECTIVES
I To estimate the duration of response time to progression overall survival and time to AML or death for MDS subjects of LDE225 days 1-28 in combination with azacitidine overall and by cohort Phase I1b
TERTIARY OBJECTIVES
I To conduct correlative studies to measure HH pathway activation and inhibition and explore biomarkers of response
II To evaluate quality of life QOL and patient-reported symptoms using the Myeloproliferative Neoplasm Symptom Assessment Form MPN-SAF and European Organization for Research and Treatment of Cancer EORTC Quality of Life Questionnaire QLQ-Core C30 in subjects treated with LDE225 in combination with azacitidine or decitabine
OUTLINE This is a dose-escalation study of erismodegib
Patients receive azacitidine subcutaneously SC or intravenously IV on days 1-7 sonidegib orally PO once daily QD on days 1-28 or 1-7 or decitabine IV on days 1-5 Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
NOTE Sonidegib PO QD is given on days 1-7 if in combination with azacitidine or on days 1-28 is given if in combination with decitabine
After completion of study treatment patients are followed up every 3 months until progressive disease and then every 6 months for 2 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2014-00866 | REGISTRY | None | None |
| Mod13-009003-08 | None | None | None |
| MC1389 | OTHER | None | None |
| P30CA015083 | NIH | Mayo Clinic | httpsreporternihgovquickSearchP30CA015083 |