Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01567709|
Recruitment Status : Active, not recruiting
First Posted : March 30, 2012
Last Update Posted : December 12, 2017
|Condition or disease||Intervention/treatment||Phase|
|Adult B Acute Lymphoblastic Leukemia Adult T Acute Lymphoblastic Leukemia Anaplastic Large Cell Lymphoma Angioimmunoblastic T-Cell Lymphoma Chronic Lymphocytic Leukemia Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue Hepatosplenic T-Cell Lymphoma Intraocular Lymphoma Lymphomatous Involvement of Non-Cutaneous Extranodal Site Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma Nodal Marginal Zone Lymphoma Primary Cutaneous B-Cell Non-Hodgkin Lymphoma Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Burkitt 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 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 Non-Hodgkin Lymphoma Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma 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 Testicular Lymphoma Waldenstrom Macroglobulinemia||Drug: Alisertib Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Vorinostat||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of the Aurora Kinase a Inhibitor MLN8237 in Combination With the Histone Deacetylase Inhibitor Vorinostat in Lymphoid Malignancies|
|Actual Study Start Date :||April 16, 2012|
|Estimated Primary Completion Date :||December 31, 2017|
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
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|