Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma
Adult B Acute Lymphoblastic Leukemia
Adult T Acute Lymphoblastic Leukemia
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-Cell Lymphoma
Chronic Lymphocytic Leukemia
Cutaneous B-Cell Non-Hodgkin Lymphoma
Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue
Hepatosplenic T-Cell Lymphoma
Lymphomatous Involvement of Non-Cutaneous Extranodal Site
Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
Nodal Marginal Zone Lymphoma
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-Cell Leukemia/Lymphoma
Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides and Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Hairy Cell Leukemia
Small Intestinal Lymphoma
Splenic Marginal Zone Lymphoma
T-Cell Large Granular Lymphocyte Leukemia
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Phase I Study of the Aurora Kinase a Inhibitor MLN8237 in Combination With the Histone Deacetylase Inhibitor Vorinostat in Lymphoid Malignancies|
- MTD of alisertib defined as the highest dose tested in which less than 33% of patients experienced dose-limiting toxicity (DLT) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v.)4.0 [ Time Frame: 21 days ]The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 4.0) and nadir or maximum values for the laboratory measures, time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.
- Clinical response rate [ Time Frame: Up to 2 years ]Summarized by exact binomial confidence intervals.
- Incidence of toxicities produced by alisertib in combination with vorinostat assessed by the NCI CTCAE version 4.0 [ Time Frame: Up to 2 years ]The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 4.0) and nadir or maximum values for the laboratory measures, time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.
- Change in AURKA expression in tissue samples by IHC and FISH [ Time Frame: Baseline to up to 2 years ]All correlative study data summaries will be descriptive.
- Degree of apoptosis, described using IHC and flow cytometry [ Time Frame: Baseline to up to 2 years ]All correlative study data summaries will be descriptive.
- Degree of proliferation described using IHC and flow cytometry [ Time Frame: Baseline to up to 2 years ]All correlative study data summaries will be descriptive.
|Actual Study Start Date:||April 16, 2012|
|Estimated Primary Completion Date:||December 31, 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (alisertib, vorinostat)
Patients receive alisertib PO BID on days 1-7 or days 1-3 and 8-10, and vorinostat PO BID on days 1-14 or days 1-5 and 8-12. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesOther: Pharmacological Study
Correlative studiesDrug: Vorinostat
I. To determine the maximum-tolerated dose (MTD) of MLN8237 (alisertib) when given in combination with vorinostat and to select a dose and schedule for further testing (recommended Phase 2 dose: RP2D) in patients with lymphoid malignancies.
II. To describe the toxicities of MLN8237 when given in combination with vorinostat on a 21-day schedule.
III. To determine any clinical responses with MLN8237 in combination with vorinostat.
IV. To compare the plasma pharmacokinetics of MLN8237 when given alone and in combination with vorinostat.
V. To perform immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis to determine aurora kinase A (AURKA) expression in archival formalin-fixed paraffin-embedded sections from the most recent available tumor specimens of patients.
VI. To perform correlative studies for apoptosis and proliferation on bone marrow and lymph node specimens, where available, obtained from patients in the expanded cohort at RP2D.
OUTLINE: This is a dose-escalation study of alisertib.
Patients receive alisertib orally (PO) twice daily (BID) on days 1-7 or days 1-3 and 8-10, and vorinostat PO BID on days 1-14 or days 1-5 and 8-12. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for at least 30 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01567709
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010|
|USC / Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|University of California Davis Comprehensive Cancer Center|
|Sacramento, California, United States, 95817|
|United States, Pennsylvania|
|Penn State Milton S Hershey Medical Center|
|Hershey, Pennsylvania, United States, 17033-0850|
|University of Pittsburgh Cancer Institute (UPCI)|
|Pittsburgh, Pennsylvania, United States, 15232|
|Principal Investigator:||Tanya Siddiqi||City of Hope Comprehensive Cancer Center|