Myelodysplastic Syndrome Clinical Trial
Official title:
Phase I/Ib Study of Azacitidine or Decitabine With Hedgehog Pathway Inhibition in Myeloid Malignancies
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.
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.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT04022785 -
PLX51107 and Azacitidine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
|
Phase 1 | |
Completed |
NCT01200355 -
Posaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome
|
Phase 4 | |
Active, not recruiting |
NCT02530463 -
Nivolumab and/or Ipilimumab With or Without Azacitidine in Treating Patients With Myelodysplastic Syndrome
|
Phase 2 | |
Completed |
NCT02057185 -
Occupational Status and Hematological Disease
|
||
Completed |
NCT01682226 -
Cord Blood With T-Cell Depleted Haplo-identical Peripheral Blood Stem Cell Transplantation for Hematological Malignancies
|
Phase 2 | |
Completed |
NCT02485535 -
Selinexor in Treating Patients With Intermediate- and High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome After Transplant
|
Phase 1 | |
Completed |
NCT03941769 -
2018-0674 - IL-7 for T-Cell Recovery Post Haplo and CB Transplant - Phase I/II
|
Phase 1/Phase 2 | |
Completed |
NCT00001637 -
Immunosuppressive Preparation Followed by Blood Cell Transplant for the Treatment of Blood Cancers in Older Adults
|
Phase 2 | |
Recruiting |
NCT06195891 -
Orca-T Following Chemotherapy and Total Marrow and Lymphoid Irradiation for the Treatment of Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia or Myelodysplastic Syndrome
|
Phase 1 | |
Active, not recruiting |
NCT04188678 -
Resiliency in Older Adults Undergoing Bone Marrow Transplant
|
N/A | |
Completed |
NCT00987480 -
Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine
|
Phase 2 | |
Recruiting |
NCT02356159 -
Study of Palifermin (Kepivance) in Persons Undergoing Unrelated Donor Allogeneic Hematopoietic Cell Transplantation
|
Phase 1/Phase 2 | |
Completed |
NCT04666025 -
SARS-CoV-2 Donor-Recipient Immunity Transfer
|
||
Completed |
NCT02756572 -
Early Allogeneic Hematopoietic Cell Transplantation in Treating Patients With Relapsed or Refractory High-Grade Myeloid Neoplasms
|
Phase 2 | |
Terminated |
NCT02877082 -
Tacrolimus, Bortezomib, & Thymoglobulin in Preventing Low Toxicity GVHD in Donor Blood Stem Cell Transplant Patients
|
Phase 2 | |
Completed |
NCT02543879 -
Study of a Novel BET Inhibitor FT-1101 in Patients With Relapsed or Refractory Hematologic Malignancies
|
Phase 1 | |
Completed |
NCT02262312 -
Iron Overload and Transient Elastography in Patients With Myelodysplastic Syndrome
|
Phase 0 | |
Completed |
NCT02188290 -
Transplant-Related Mortality in Patients Undergoing a Peripheral Blood Stem Cell Transplantation or an Umbilical Cord Blood Transplantation
|
N/A | |
Recruiting |
NCT02330692 -
Cohort Study of New Prognostic Factors With Peripheral Blood and Bone Marrow Evaluation at the Time of Diagnosis and Relapse in Myelodysplastic Syndrome
|
||
Completed |
NCT01684150 -
A Phase 1, Open-Label, Dose-Escalation & Expanded Cohort, Continuous IV Infusion, Multi-center Study of the Safety, Tolerability,PK & PD of EPZ-5676 in Treatment Relapsed/Refractory Patients With Leukemias Involving
|
Phase 1 |