Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma
Phase I Study of the Aurora Kinase a Inhibitor MLN8237 in Combination With the Histone Deacetylase Inhibitor Vorinostat in Lymphoid Malignancies
9 other identifiers
interventional
34
1 country
5
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Apr 2012
Longer than P75 for phase_1
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 29, 2012
CompletedFirst Posted
Study publicly available on registry
March 30, 2012
CompletedStudy Start
First participant enrolled
April 16, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 29, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
March 29, 2018
CompletedApril 11, 2018
April 1, 2018
6 years
March 29, 2012
April 10, 2018
Conditions
Outcome Measures
Primary Outcomes (1)
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
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.
21 days
Secondary Outcomes (2)
Incidence of toxicities produced by alisertib in combination with vorinostat assessed by the NCI CTCAE version 4.0
Up to 2 years
Clinical response rate
Up to 2 years
Other Outcomes (3)
Degree of apoptosis, described using IHC and flow cytometry
Baseline to up to 2 years
Degree of proliferation described using IHC and flow cytometry
Baseline to up to 2 years
Change in AURKA expression in tissue samples by IHC and FISH
Baseline to up to 2 years
Study Arms (1)
Treatment (alisertib, vorinostat)
EXPERIMENTALPatients 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.
Interventions
Given PO
Given PO
Eligibility Criteria
You may qualify if:
- Patients must have a histologically or cytologically confirmed lymphoid malignancy (like Hodgkin lymphoma or one of the mature B- or T-cell non-Hodgkin lymphomas as classified by World Health Organization \[WHO\]) for which standard curative or palliative measures do not exist or are no longer effective
- Patients must have measurable disease in two dimensions and \>= 2 cm is acceptable (or 1.5 cm if 0.5 slices are used, as in spiral computed tomography \[CT\] scans); lesions that are considered intrinsically non-measurable include the following:
- Bone lesions
- Leptomeningeal disease
- Ascites
- Pleural/pericardial effusion
- Inflammatory breast disease
- Lymphangitis cutis/pulmonis
- Abdominal masses that are not confirmed and followed by imaging techniques
- Cystic lesions
- Lesions that are situated in a previously irradiated area
- Patients must have had at least 1 prior systemic chemotherapy (not just steroids or local radiation); last chemotherapy or radiation must be at least 4 weeks prior to enrollment on this study; patients who decline other potentially curative therapy may be eligible; prior radiation therapy must not have been to more than 25% of the bone marrow; whole pelvic radiation is considered to be over 25%
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Life expectancy of greater than 12 weeks
- Absolute neutrophil count \>= 1,500/mcL
- +8 more criteria
You may not qualify if:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients who are receiving any other investigational agents
- 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
- Treatment with valproic acid within 14 days prior to initiation of study and during the study
- Prior use of valproic acid or any other histone deacetylase (HDAC) inhibitor for lymphoma treatment
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with MLN8237
- Human Immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
- 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, histamine (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 with New York Heart Association (NYHA) class II-IV heart failure
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Related Publications (1)
Siddiqi T, Frankel P, Beumer JH, Kiesel BF, Christner S, Ruel C, Song JY, Chen R, Kelly KR, Ailawadhi S, Kaesberg P, Popplewell L, Puverel S, Piekarz R, Forman SJ, Newman EM. Phase 1 study of the Aurora kinase A inhibitor alisertib (MLN8237) combined with the histone deacetylase inhibitor vorinostat in lymphoid malignancies. Leuk Lymphoma. 2020 Feb;61(2):309-317. doi: 10.1080/10428194.2019.1672052. Epub 2019 Oct 16.
PMID: 31617432DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Tanya Siddiqi
City of Hope Comprehensive Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 29, 2012
First Posted
March 30, 2012
Study Start
April 16, 2012
Primary Completion
March 29, 2018
Study Completion
March 29, 2018
Last Updated
April 11, 2018
Record last verified: 2018-04