Alisertib and Romidepsin in Treating Patients With Relapsed or Refractory B-Cell or T-Cell Lymphomas
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|ClinicalTrials.gov Identifier: NCT01897012|
Recruitment Status : Completed
First Posted : July 11, 2013
Last Update Posted : January 28, 2019
|Condition or disease||Intervention/treatment||Phase|
|MYC Positive Recurrent B-Cell Non-Hodgkin Lymphoma Recurrent Burkitt Lymphoma Recurrent Diffuse Large B-Cell Lymphoma Recurrent Follicular Lymphoma Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements Recurrent Hodgkin Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma Refractory B-Cell Non-Hodgkin Lymphoma Refractory Burkitt Lymphoma Refractory Diffuse Large B-Cell Lymphoma Refractory Follicular Lymphoma Refractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements Refractory Hodgkin Lymphoma Refractory Mantle Cell Lymphoma Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma||Drug: Alisertib Other: Laboratory Biomarker Analysis Drug: Romidepsin||Phase 1|
I. To assess the safety profile of alisertib (MLN8237) plus romidepsin. II. To determine the maximum tolerated dose (MTD), if reached, of MLN8237 administered in combination with romidepsin.
I. To evaluate objective response rate (ORR) and complete response (CR) of the combined regimen.
II. To assess whether higher levels of expression of aurora kinase A correlate with outcomes.
III. To determine if this combination results in downregulation of targets of v-myc myelocytomatosis viral oncogene homolog (avian) (C-Myc) in C-Myc positive patients, induces mitotic catastrophe, changes immune system or other host responses, or upregulates markers for apoptosis.
OUTLINE: This is a dose-escalation study.
Patients receive alisertib orally (PO) twice daily (BID) on days 1-7 (dose levels 1-4) or days 1-3, 8-10, and 15-17 (dose levels 5-8). Patients also receive romidepsin intravenously (IV) over 4 hours on days 1 and 8 (dose levels 1-4) or 2, 9, and 16 (dose levels 5-8). Treatment repeats every 21 days (dose levels 1-4) or 28 days (dose levels 5-8) for up to 8 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Trial of MLN8237 Plus Romidepsin for Relapsed/Refractory Aggressive B-Cell and T-Cell Lymphomas|
|Actual Study Start Date :||July 17, 2013|
|Actual Primary Completion Date :||October 31, 2018|
|Actual Study Completion Date :||November 30, 2018|
Experimental: Treatment (alisertib, romidepsin)
Patients receive alisertib PO BID on days 1-7 (dose levels 1-4) or days 1-3, 8-10, and 15-17 (dose levels 5-8). Patients also receive romidepsin IV over 4 hours on days 1 and 8 (dose levels 1-4) or 2, 9, and 16 (dose levels 5-8). Treatment repeats every 21 days (dose levels 1-4) or 28 days (dose levels 5-8) for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Incidence of adverse events as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (utilized for adverse event reporting beginning April 1, 2018) [ Time Frame: Up to 4 weeks post-treatment ]
- Maximum tolerated dose graded according to NCI CTCAE version 5.0 [ Time Frame: Up to 28 days ]Maximum tolerated dose is defined as the highest dose level at which 6 patients have been treated with fewer than 2 instances of dose-limiting toxicities.
- Overall response rate [ Time Frame: Up to 4 weeks post-treatment ]Point estimates along with 95% confidence intervals will be provided.
- Complete response [ Time Frame: Up to 4 weeks post-treatment ]Point estimates along with 95% confidence intervals will be provided.
- Aurora A kinase expression intensity, assessed by immunohistochemistry [ Time Frame: Baseline ]Will be correlated with response.
- Change in gene expression profiles [ Time Frame: Baseline to up to 28 days (course 1) ]Will be correlated with response.
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): NCT01897012
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Hun Lee||M.D. Anderson Cancer Center|