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Alisertib and Romidepsin in Treating Patients With Relapsed or Refractory B-Cell or T-Cell Lymphomas | Clinical Trials | Clareo Health

COMPLETEDPHASE1

Alisertib and Romidepsin in Treating Patients With Relapsed or Refractory B-Cell or T-Cell Lymphomas

A Phase 1 Trial of MLN8237 Plus Romidepsin for Relapsed/Refractory Aggressive B-Cell and T-Cell Lymphomas

NCT01897012•National Cancer Institute (NCI)

View on ClinicalTrials.gov

Summary

This phase I trial studies the side effects and best dose of alisertib and romidepsin in treating patients with B-cell or T-cell lymphomas that have returned after a period of improvement (relapsed) or have not responded to treatment (refractory). Alisertib and romidepsin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Patients must have histologically or cytologically confirmed Hodgkin lymphoma, Burkitt's lymphoma, double-hit lymphoma, other c-Myc positive B-cell lymphoma, diffuse large-B cell lymphoma including those patients with history of transformed follicular lymphoma, mantle cell lymphoma, or peripheral T-cell lymphoma
•Patients must have at least one 1.5 cm bidimensional measurable lesion
•Relapsed or refractory after at least 1 front-line therapy
•Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
•Life expectancy of greater than 12 weeks
•Absolute neutrophil count \>= 1,500/mcL
•Platelets \>= 75,000/mcL
•Direct bilirubin =\< 1 mg/dL
•Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal
•Creatinine =\< 2 x institutional upper limits of normal
+3 more criteria

Exclusion Criteria

•Patients who have had chemotherapy, radiation therapy, or other investigational agents within 3 weeks prior to entering study, 6 weeks for nitrosoureas or mitomycin
•Patients with known brain metastases should be excluded from this clinical trial
•History of allergic reactions attributed to compounds of similar chemical or biologic composition to MLN8237, including but not limited to established allergic reaction to benzodiazepines, or romidepsin; agents that alter gastric pH may change MLN8237 absorption are not permitted; proton pump inhibitors need to be stopped 4 days prior to the first dose of MLN8237; histamine-2 (H2) receptor antagonists are not permitted from the day prior (day -1) through to the end of MLN8237 dosing; antacid preparations are not permitted for 2 hours before or 2 hours after administration of MLN8237
•Co-administration of enzyme-inducing antiepileptic drugs, rifampin, rifabutin, rifapentine, or St. John's wort is not permitted; concurrent bisphosphonate therapy is allowed if it was started before study entry and is maintained at recommended dosing intervals; bisphosphonate therapy may not be initiated after study entry
•Any serious active disease or co-morbid condition, which in the opinion of the principal investigator, will interfere with the safety or compliance of the trial
•Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with MLN8237 and/or romidepsin
•Ejection fraction (EF) \< 40% or myocardial infarction (MI) within the past 3 months; known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen; or any conditions that could result in excessive toxicity associated with the benzodiazepine-like effects of MLN8237
•Requirement for constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes; intermittent uses of antacids or H2 antagonists are allowed
•Inability to swallow oral medication or to maintain a fast as required for 2 hours before and 1 hour after MLN8237 administration or any condition that would modify small bowel absorption of oral medications, including malabsorption, or resection of pancreas or upper bowel; treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine, oxcarbazepine, primidone or phenobarbital, or rifampin, rifabutin, rifapentine, or St. John's wort within 14 days prior to the first dose of MLN8237 and during the study; patients must be cautiously co-medicated with agents that cause corrected QT interval (QTc) prolongation and agents that are strong or moderate enzyme inhibitors during the study

Locations (1)

M D Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

July 17, 2013

Primary Completion Date

October 31, 2018

Completion Date

November 30, 2018

Last Updated

January 28, 2019

Enrollment

ACTUAL participants

Conditions

MYC PositiveRecurrent B-Cell Non-Hodgkin LymphomaRecurrent Burkitt LymphomaRecurrent Diffuse Large B-Cell LymphomaRecurrent Follicular LymphomaRecurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 RearrangementsRecurrent Hodgkin LymphomaRecurrent Mantle Cell LymphomaRecurrent Mature T- and NK-Cell Non-Hodgkin LymphomaRefractory B-Cell Non-Hodgkin LymphomaRefractory Burkitt LymphomaRefractory Diffuse Large B-Cell LymphomaRefractory Follicular LymphomaRefractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 RearrangementsRefractory Hodgkin LymphomaRefractory Mantle Cell LymphomaRefractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma

Interventions

Alisertib

DRUG

Laboratory Biomarker Analysis

OTHER

Romidepsin

DRUG

Nivolumab and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

NCT03015896

Grade 3a Follicular LymphomaRecurrent Burkitt Lymphoma+13 more

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ACTIVE_NOT_RECRUITINGPHASE1

An Early Phase Study of Venetoclax, Lenalidomide, and Rituximab/Hyaluronidase in Slow-Growing Lymphomas That Have Come Back After Treatment or Have Not Responded to Treatment

NCT04447716

Recurrent B-Cell Non-Hodgkin LymphomaRecurrent Follicular Lymphoma+6 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: January 28, 2019Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Alisertib and Romidepsin in Treating Patients With Relapsed or Refractory B-Cell or T-Cell Lymphomas

Inclusion Criteria

Exclusion Criteria

Nivolumab and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

An Early Phase Study of Venetoclax, Lenalidomide, and Rituximab/Hyaluronidase in Slow-Growing Lymphomas That Have Come Back After Treatment or Have Not Responded to Treatment

TTI-622 in Combination With Pembrolizumab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Gene Therapy in Treating Patients With Human Immunodeficiency Virus-Related Lymphoma Receiving Stem Cell Transplant

R-ICE and Lenalidomide in Treating Patients With First-Relapse/Primary Refractory Diffuse Large B-Cell Lymphoma

Dose Adjusted EPOCH Regimen in Combination With Ofatumumab or Rituximab in Treating Patients With Newly Diagnosed or Relapsed or Refractory Burkitt Lymphoma or Relapsed or Refractory Acute Lymphoblastic Leukemia