Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma
This phase I trial studies the side effects and the best dose of alisertib when given together with vorinostat in treating patients with Hodgkin lymphoma, B-cell non-Hodgkin lymphoma, or peripheral T-cell lymphoma that has come back. Alisertib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
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:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
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 ] [ Designated as safety issue: Yes ]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.
- Incidence of toxicities produced by alisertib in combination with vorinostat assessed by the NCI CTCAE version 4.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]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 ] [ Designated as safety issue: No ]Summarized by exact binomial confidence intervals.
- Degree of apoptosis, described using IHC and flow cytometry [ Time Frame: Baseline to up to 2 years ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]All correlative study data summaries will be descriptive.
- Change in AURKA expression in tissue samples by IHC and FISH [ Time Frame: Baseline to up to 2 years ] [ Designated as safety issue: No ]All correlative study data summaries will be descriptive.
|Study Start Date:||April 2012|
|Estimated Primary Completion Date:||April 2015 (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:Drug: Vorinostat
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesOther: Pharmacological Study
Other Name: pharmacological studies
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||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Tanya Siddiqi 626-256-4673 email@example.com|
|Principal Investigator: Tanya Siddiqi|
|USC / Norris Comprehensive Cancer Center||Recruiting|
|Los Angeles, California, United States, 90033|
|Contact: Kevin R. Kelly 323-224-7371 firstname.lastname@example.org|
|Principal Investigator: Kevin R. Kelly|
|University of California Davis Comprehensive Cancer Center||Recruiting|
|Sacramento, California, United States, 95817|
|Contact: Joseph M. Tuscano 916-734-3771 email@example.com|
|Principal Investigator: Joseph M. Tuscano|
|United States, Pennsylvania|
|Penn State Milton S Hershey Medical Center||Recruiting|
|Hershey, Pennsylvania, United States, 17033-0850|
|Contact: W. C. Ehmann 717-531-5059 firstname.lastname@example.org|
|Principal Investigator: W. C. Ehmann|
|University of Pittsburgh Cancer Institute||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15232|
|Contact: Jan H. Beumer 412-623-3216 email@example.com|
|Principal Investigator: Jan H. Beumer|
|Principal Investigator:||Tanya Siddiqi||Beckman Research Institute|