Clinical trial NCT01466881: Alisertib in Treating Patients With Relapsed or Refractory Peripheral T-Cell Non-Hodgkin Lymphoma
Official title: Phase II Trial of the Aurora Kinase A Inhibitor MLN8237, in Relapsed or Refractory Peripheral T-Cell Non-Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Nasal Type Extranodal NK/T-Cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-Cell Lymphoma
Hepatosplenic T-Cell Lymphoma
Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
Recurrent Adult Non-Hodgkin Lymphoma
Recurrent Adult T-Cell Leukemia/Lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2011-11-08
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial studies how well alisertib works in treating patients with peripheral T-cell non-Hodgkin lymphoma that has come back after a period of improvement or has not responded to treatment. Alisertib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed description: PRIMARY OBJECTIVES:

I. To estimate the objective response rate (complete responses + partial responses) after treatment with alisertib (MLN8237) in patients with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma.

II. To assess overall survival (OS) and progression-free survival (PFS) in this patient population.

III. To evaluate the safety and tolerability of MLN8237 treatment for this patient population.

IV. To explore the association between pre-treatment aurora kinase A expression in tumor biopsies as measured by fluorescence in situ hybridization (FISH) and objective response rate in patients with peripheral T-cell lymphomas (PTCL) treated with MLN8237.

IV. To investigate the copy number, mutational status, expression of aurora kinase (A, B, and C) and associated signaling pathways in PTCL utilizing tissue microarray analysis (TMA) before and after treatment with MLN8237.

V. To investigate changes in the serum cytokine profile pre- and post- aurora kinase Inhibitor treatment.

VI. To evaluate serum markers of apoptosis pre- and post- aurora kinase inhibitor treatment as pharmacodynamic markers of efficacy.

OUTLINE:

Patients receive alisertib orally (PO) twice daily (BID) on days 1-7. Treatment repeats every 21 days for 17 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 months for 2 years.

Eligibility criteria: Inclusion Criteria:

* Patients must have histologically or cytologically confirmed relapsed/refractory non-Hodgkin lymphoma (NHL) having progressed after a minimum of one systemic therapy with any of the following T-cell histologies:

  * Peripheral T-cell NHL (PTCL) not otherwise specified (NOS)
  * Anaplastic large cell T-cell lymphoma (ALCL) that is anaplastic lymphoma kinase either positive or negative
  * Angioimmunoblastic T-cell NHL
  * Subcutaneous panniculitis-like T-cell lymphoma
  * Enteropathy-associated T-cell NHL
  * Hepatosplenic T-cell lymphomas
  * Extranodal natural killer (NK)/T-cell lymphoma, nasal type
  * Adult T-cell leukemia/lymphoma
  * Unclassifiable PTCL
  * Transformed cutaneous T-cell lymphoma (CTCL) to PTCL with systemic involvement (not local skin transformation)
  * No other histologies are eligible; examples of ineligible histologies include: T-cell prolymphocytic leukemia, T-cell large granular lymphocytic leukemia, NK-cell leukemia, mycosis fungoides, Sezary syndrome, lymphomatoid papulosis, and primary CTCL
* Patients must have received at least one course of prior systemic therapy which may include chemotherapy, antibody therapy, or immunotherapy; for all forms of systemic therapy, patients must have completed therapy at least 21 days prior to registration; patients must not be within 84 days of radioimmunotherapy; steroids at a low dose for control of itching (up to the equivalent of 20 mg of prednisone daily) are allowed
* Patients may have received prior radiation in combination with systemic therapy; patients must not be within 21 days of external beam radiation therapy
* Patients must not have received a previous allogeneic stem cell transplant or be within 90 days of an autologous stem cell transplant
* Adequate sections and a paraffin block from the relapsed/refractory specimen must be submitted for review by the lymphoma pathology group; an adequate biopsy requires sufficient tissue to establish the architecture and a Revised European American Lymphoma (REAL) or World Health Organization (WHO) histologic subtype with certainty; thus, core biopsies, especially multiple core biopsies MAY be adequate; whereas, needle aspirations or cytologies are not adequate
* Patients must have bidimensionally measurable disease within 28 days prior to registration; a diagnostic quality computed tomography (CT) scan of the chest abdomen, pelvis, neck and positron emission tomography (PET)/CT must be performed within 28 days of registration (PET/CT scan can be done instead of separate PET and CT scans only if the CT component is a diagnostic CT with contrast); patients who also have non-measurable disease in addition to measurable disease must have all non-measurable disease assessed within 42 days prior to registration
* Patients must have a bilateral or unilateral bone marrow aspirate and biopsy performed within 42 days prior to registration
* Patients must not have clinical evidence of central nervous system involvement by lymphoma; any laboratory tests that are performed to assess clinical signs of central nervous system involvement must have been performed within 42 days prior to registration, and the results must be negative
* Patients must be able to swallow tablets
* Patients known to be human immunodeficiency virus (HIV)-positive must not have multi-drug resistant HIV infection, CD4 counts \< 150/mcL, or other concurrent acquired immunodeficiency syndrome (AIDS)-defining conditions
* Patients must be offered the opportunity to consent to the banking of specimens for future use
* Absolute granulocyte count \>= 1,500 cells/mcL; patients with documented marrow involvement may be transfused to this value
* Platelet count \>= 75,000 cells/mcL; patients with documented marrow involvement may be transfused to this value
* Serum creatinine (mg/dL) =\< institutional upper limit of normal (IULN) obtained within 14 days prior to registration
* Calculated creatinine clearance \> 50 ml/min; the serum creatinine value used in the calculation must have been obtained within 14 days prior to registration
* Serum bilirubin =\< 2 times institutional upper limit of normal
* Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =\< 2.5 x IULN
* Serum lactate dehydrogenase (LDH) obtained within 14 days prior to registration
* Patients must have a Zubrod performance status of 0, 1, or 2
* Patients must NOT have New York Heart Association (NYHA) class II-IV heart failure
* No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
* Pregnant or nursing women are not eligible; women/men of reproductive potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for 4 months after completion of MLN8237 administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the patient should inform the treating physician immediately
* All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

Primary outcomes:
measure: Objective Response Rate (Complete Responses (CR) + Partial Responses (PR))
timeFrame: Up to 1 year after registration
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 2 years after registration
measure: Progression Free Survival (PFS)
timeFrame: Up to 2 years after registration
measure: To Evaluate the Safety and Tolerability of MLN8237 (Number of With Grade 3 Through Grade 5 Adverse Events That Are Related to MLN8237)
timeFrame: Up to 1 year after registration
Other outcomes:
measure: Aurora Kinase A Expression
timeFrame: Baseline
Locations:
city: Mobile
country: United States
facility: Providence Hospital
state: Alabama
city: Tucson
country: United States
facility: The University of Arizona Cancer Center-Orange Grove Campus
state: Arizona
city: Tucson
country: United States
facility: The University of Arizona Cancer Center-North Campus
state: Arizona
city: Tucson
country: United States
facility: The University of Arizona Medical Center-University Campus
state: Arizona
city: Berkeley
country: United States
facility: Alta Bates Summit Medical Center-Herrick Campus
state: California
city: Burlingame
country: United States
facility: Mills - Peninsula Hospitals
state: California
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Novato
country: United States
facility: Sutter Cancer Research Consortium
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center-Pacific Campus
state: California
city: Santa Rosa
country: United States
facility: Sutter Pacific Medical Foundation
state: California
city: Vallejo
country: United States
facility: Sutter Solano Medical Center/Cancer Center
state: California
city: Hartford
country: United States
facility: Saint Francis Hospital and Medical Center
state: Connecticut
city: Lewes
country: United States
facility: Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University/Winship Cancer Institute
state: Georgia
city: Aiea
country: United States
facility: Oncare Hawaii Inc-Pali Momi
state: Hawaii
city: Aiea
country: United States
facility: Pali Momi Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: Oncare Hawaii Inc-POB II
state: Hawaii
city: Honolulu
country: United States
facility: Queen's Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: Straub Clinic and Hospital
state: Hawaii
city: Honolulu
country: United States
facility: University of Hawaii Cancer Center
state: Hawaii
city: Honolulu
country: United States
facility: OnCare Hawaii-Liliha
state: Hawaii
city: Honolulu
country: United States
facility: Kuakini Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: Oncare Hawaii Inc-Kuakini
state: Hawaii
city: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children
state: Hawaii
city: Kailua
country: United States
facility: Castle Medical Center
state: Hawaii
city: Lihue
country: United States
facility: Wilcox Memorial Hospital and Kauai Medical Clinic
state: Hawaii
city: Boise
country: United States
facility: Saint Alphonsus Cancer Care Center-Boise
state: Idaho
city: Chicago
country: United States
facility: Hematology and Oncology Associates
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Highland Park
country: United States
facility: Hematology Oncology Associates of Illinois-Highland Park
state: Illinois
city: Kankakee
country: United States
facility: Presence Saint Mary's Hospital
state: Illinois
city: Libertyville
country: United States
facility: North Shore Hematology Oncology
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Niles
country: United States
facility: Illinois Cancer Specialists-Niles
state: Illinois
city: Skokie
country: United States
facility: Hematology Oncology Associates of Illinois - Skokie
state: Illinois
city: Ames
country: United States
facility: McFarland Clinic PC-William R Bliss Cancer Center
state: Iowa
city: Ottumwa
country: United States
facility: Ottumwa Regional Health Center
state: Iowa
city: Chanute
country: United States
facility: Cancer Center of Kansas - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas - El Dorado
state: Kansas
city: Fort Scott
country: United States
facility: Cancer Center of Kansas - Fort Scott
state: Kansas
city: Independence
country: United States
facility: Cancer Center of Kansas-Independence
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas-Kingman
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Liberal
country: United States
facility: Cancer Center of Kansas-Liberal
state: Kansas
city: McPherson
country: United States
facility: Cancer Center of Kansas - McPherson
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas - Newton
state: Kansas
city: Overland Park
country: United States
facility: Menorah Medical Center
state: Kansas
city: Overland Park
country: United States
facility: Saint Luke's South Hospital
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas - Parsons
state: Kansas
city: Prairie Village
country: United States
facility: Kansas City CCOP
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates In Womens Health
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas-Wichita Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas - Main Office
state: Kansas
city: Wichita
country: United States
facility: Via Christi Regional Medical Center
state: Kansas
city: Wichita
country: United States
facility: Wichita CCOP
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas - Winfield
state: Kansas
city: Baton Rouge
country: United States
facility: Hematology/Oncology Clinic LLP
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center Shreveport
state: Louisiana
city: Elkton MD
country: United States
facility: Union Hospital of Cecil County
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Hospital
state: Michigan
city: Ann Arbor
country: United States
facility: Michigan Cancer Research Consortium CCOP
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Hospital and Medical Center
state: Michigan
city: Detroit
country: United States
facility: Saint John Hospital and Medical Center
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Genesys Regional Medical Center-West Flint Campus
state: Michigan
city: Grand Blanc
country: United States
facility: Genesys Regional Medical Center
state: Michigan
city: Jackson
country: United States
facility: Allegiance Health
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Lansing
country: United States
facility: Sparrow Hospital
state: Michigan
city: Livonia
country: United States
facility: Saint Mary Mercy Hospital
state: Michigan
city: Pontiac
country: United States
facility: Saint Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: Saint Joseph Mercy Port Huron
state: Michigan
city: Saginaw
country: United States
facility: Saint Mary's of Michigan
state: Michigan
city: Warren
country: United States
facility: Saint John Macomb-Oakland Hospital
state: Michigan
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy Hospital
state: Minnesota
city: Edina
country: United States
facility: Fairview-Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Unity Hospital
state: Minnesota
city: Hutchinson
country: United States
facility: Hutchinson Area Health Care
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology PA-Maplewood
state: Minnesota
city: Maplewood
country: United States
facility: Saint John's Hospital - Healtheast
state: Minnesota
city: Minneapolis
country: United States
facility: Abbott-Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: New Ulm
country: United States
facility: New Ulm Medical Center
state: Minnesota
city: Robbinsdale
country: United States
facility: North Memorial Medical Health Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: Metro-Minnesota NCI Community Oncology Research Program
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Clinic - Saint Louis Park
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Shakopee
country: United States
facility: Saint Francis Regional Medical Center
state: Minnesota
city: Stillwater
country: United States
facility: Lakeview Hospital
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Willmar
country: United States
facility: Rice Memorial Hospital
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology and Hematology PA-Woodbury
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Kansas City
country: United States
facility: Saint Joseph Health Center
state: Missouri
city: Kansas City
country: United States
facility: North Kansas City Hospital
state: Missouri
city: Kansas City
country: United States
facility: Heartland Hematology and Oncology Associates Incorporated
state: Missouri
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Lee's Summit
country: United States
facility: Saint Luke's East - Lee's Summit
state: Missouri
city: Liberty
country: United States
facility: Liberty Radiation Oncology Center
state: Missouri
city: Saint Joseph
country: United States
facility: Heartland Regional Medical Center
state: Missouri
city: Saint Joseph
country: United States
facility: Saint Joseph Oncology Inc
state: Missouri
city: Saint Louis
country: United States
facility: Saint Louis University Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Springfield
country: United States
facility: Cancer Research for the Ozarks NCORP
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Springfield
country: United States
facility: CoxHealth South Hospital
state: Missouri
city: Billings
country: United States
facility: Montana Cancer Consortium CCOP
state: Montana
city: Billings
country: United States
facility: Saint Vincent Healthcare
state: Montana
city: Billings
country: United States
facility: Frontier Cancer Center and Blood Institute-Billings
state: Montana
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Cancer Center
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Hospital
state: Montana
city: Butte
country: United States
facility: Saint James Community Hospital and Cancer Treatment Center
state: Montana
city: Great Falls
country: United States
facility: Benefis Healthcare- Sletten Cancer Institute
state: Montana
city: Great Falls
country: United States
facility: Big Sky Oncology
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic
state: Montana
city: Havre
country: United States
facility: Northern Montana Hospital
state: Montana
city: Helena
country: United States
facility: Saint Peter's Community Hospital
state: Montana
city: Kalispell
country: United States
facility: Glacier Oncology PLLC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Medical Oncology
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists
state: Montana
city: Missoula
country: United States
facility: Saint Patrick Hospital - Community Hospital
state: Montana
city: Camden
country: United States
facility: Cooper Hospital University Medical Center
state: New Jersey
city: New York
country: United States
facility: Laura and Issac Perlmutter Cancer Center at NYU Langone
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Statesville
country: United States
facility: Iredell Memorial Hospital
state: North Carolina
city: Bismarck
country: United States
facility: Mid Dakota Clinic
state: North Dakota
city: Bismarck
country: United States
facility: Saint Alexius Medical Center
state: North Dakota
city: Bismarck
country: United States
facility: Sanford Bismarck Medical Center
state: North Dakota
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Salem
country: United States
facility: Salem Hospital
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Hospital-Cedar Crest
state: Pennsylvania
city: Charleston
country: United States
facility: Roper Hospital
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: San Antonio
country: United States
facility: Audie L Murphy Veterans Affairs Hospital
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
state: Texas
city: San Antonio
country: United States
facility: University Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Johnson Creek
country: United States
facility: UW Cancer Center Johnson Creek
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: New Richmond
country: United States
facility: Cancer Center of Western Wisconsin
state: Wisconsin
city: Casper
country: United States
facility: Rocky Mountain Oncology
state: Wyoming
city: Sheridan
country: United States
facility: Welch Cancer Center
state: Wyoming
city: Vancouver
country: Canada
facility: BCCA-Vancouver Cancer Centre
state: British Columbia
Study officials:
affiliation: SWOG Cancer Research Network
name: Paul Barr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Barr PM, Li H, Spier C, Mahadevan D, LeBlanc M, Ul Haq M, Huber BD, Flowers CR, Wagner-Johnston ND, Horwitz SM, Fisher RI, Cheson BD, Smith SM, Kahl BS, Bartlett NL, Friedberg JW. Phase II Intergroup Trial of Alisertib in Relapsed and Refractory Peripheral T-Cell Lymphoma and Transformed Mycosis Fungoides: SWOG 1108. J Clin Oncol. 2015 Jul 20;33(21):2399-404. doi: 10.1200/JCO.2014.60.6327. Epub 2015 Jun 15.