Trials / Completed

CompletedNCT02129101

Azacitidine and Sonidegib or Decitabine in Treating Patients With Myeloid Malignancies

Phase I/Ib Study of Azacitidine or Decitabine With Hedgehog Pathway Inhibition in Myeloid Malignancies

Status: Completed
Phase: Phase 1
Study type: Interventional
Enrollment: 63 (actual)

Sponsor: Mayo Clinic · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase I/Ib 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 (AML)/chronic myelomonocytic leukemia (CMML)/myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) overlap; relapsed/refractory AML/CMML/MDS/MPN 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 I/1b) 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 (C)30 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.

Conditions

Interventions

Type	Name	Description
DRUG	Azacitidine	Given SC or IV
DRUG	Decitabine	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Quality-of-Life Assessment	Ancillary studies
DRUG	Sonidegib	Given PO

Timeline

Start date: 2014-05-01
Primary completion: 2016-12-31
Completion: 2019-10-25
First posted: 2014-05-02
Last updated: 2019-10-30

Locations

1 site across 1 country: United States

Source: ClinicalTrials.gov record NCT02129101. Inclusion in this directory is not an endorsement.