Alisertib in Treating Patients With Relapsed or Refractory Peripheral T-Cell Non-Hodgkin Lymphoma

Phase 2

Completed

Conditions: Hepatosplenic T-Cell Lymphoma
Recurrent Adult T-Cell Leukemia/Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-Cell Lymphoma
Recurrent Adult Non-Hodgkin Lymphoma
Adult Nasal Type Extranodal NK/T-Cell Lymphoma
Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma

Interventions: Drug: Alisertib
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study

Registration Number: NCT01466881

Lead Sponsor: National Cancer Institute (NCI)

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 42

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (alisertib)	Laboratory Biomarker Analysis	Patients receive alisertib PO BID on days 1-7. Treatment repeats every 21 days for 17 courses in the absence of disease progression or unacceptable toxicity.
Treatment (alisertib)	Pharmacological Study	Patients receive alisertib PO BID on days 1-7. Treatment repeats every 21 days for 17 courses in the absence of disease progression or unacceptable toxicity.
Treatment (alisertib)	Alisertib	Patients receive alisertib PO BID on days 1-7. Treatment repeats every 21 days for 17 courses in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (Complete Responses (CR) + Partial Responses (PR))	Up to 1 year after registration	Objective disease status is evaluated according to the 2007 revised Cheson et al. criteria. Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow (BM) must be negative if positive at baseline. Normalization of markers. Partial Response(PR) is a 50% decrease in the SPD for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Up to 2 years after registration	Measure from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Progression Free Survival (PFS)	Up to 2 years after registration	Measured from date of registration to date of first observation of progressive disease or death due to any cause. Patients last known to be alive and without report of progressive disease are censored at date of last contact. Progressive disease is at least 50% increase in the sum of the product of the diameters (SPD) of target measurable nodal lesions over the smallest sum observed or ≥ 50% increase in the greatest transverse diameter (GTD) of any node \> 1 cm in shortest axis, or ≥ 50% increase in the SPD of other target measurable lesions over the smallest sum observed. New bone marrow involvement. New lesion \> 1.5 cm in longest axis, or ≥ 50% increase in GTD of any previously involved node with a diameter ≤ 1.0 cm in the short axis such that its longest axis is now \> 1.5 cm. Lymph nodes with long axis is \> 1.5 cm, or if the both the long and short axes are \> 1 cm. PET should be positive if positive PET at baseline.
To Evaluate the Safety and Tolerability of MLN8237 (Number of With Grade 3 Through Grade 5 Adverse Events That Are Related to MLN8237)	Up to 1 year after registration	Incidence of toxicity as assessed by the Common Terminology Criteria for Adverse Events version 4.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.

Trial Locations

Locations (161): Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
United Hospital
🇺🇸
Saint Paul, Minnesota, United States
Sparrow Hospital
🇺🇸
Lansing, Michigan, United States
Minnesota Oncology and Hematology PA-Woodbury
🇺🇸
Woodbury, Minnesota, United States
Saint Patrick Hospital - Community Hospital
🇺🇸
Missoula, Montana, United States
Mercy Hospital Springfield
🇺🇸
Springfield, Missouri, United States
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
Queen's Medical Center
🇺🇸
Honolulu, Hawaii, United States
Straub Clinic and Hospital
🇺🇸
Honolulu, Hawaii, United States
University of Hawaii Cancer Center
🇺🇸
Honolulu, Hawaii, United States
OnCare Hawaii-Liliha
🇺🇸
Honolulu, Hawaii, United States
Roper Hospital
🇺🇸
Charleston, South Carolina, United States
Providence Hospital
🇺🇸
Mobile, Alabama, United States
Alta Bates Summit Medical Center-Herrick Campus
🇺🇸
Berkeley, California, United States
Sutter Pacific Medical Foundation
🇺🇸
Santa Rosa, California, United States
Emory University/Winship Cancer Institute
🇺🇸
Atlanta, Georgia, United States
Hematology and Oncology Associates
🇺🇸
Chicago, Illinois, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
Presence Saint Mary's Hospital
🇺🇸
Kankakee, Illinois, United States
Illinois Cancer Specialists-Niles
🇺🇸
Niles, Illinois, United States
Hematology Oncology Associates of Illinois - Skokie
🇺🇸
Skokie, Illinois, United States
McFarland Clinic PC-William R Bliss Cancer Center
🇺🇸
Ames, Iowa, United States
Ottumwa Regional Health Center
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Ottumwa, Iowa, United States
Cancer Center of Kansas - McPherson
🇺🇸
McPherson, Kansas, United States
Cancer Center of Kansas - Newton
🇺🇸
Newton, Kansas, United States
City of Hope Comprehensive Cancer Center
🇺🇸
Duarte, California, United States
Sutter Solano Medical Center/Cancer Center
🇺🇸
Vallejo, California, United States
Sutter Cancer Research Consortium
🇺🇸
Novato, California, United States
Hematology Oncology Associates of Illinois-Highland Park
🇺🇸
Highland Park, Illinois, United States
North Shore Hematology Oncology
🇺🇸
Libertyville, Illinois, United States
Saint Joseph Oncology Inc
🇺🇸
Saint Joseph, Missouri, United States
Hurley Medical Center
🇺🇸
Flint, Michigan, United States
Genesys Regional Medical Center-West Flint Campus
🇺🇸
Flint, Michigan, United States
Borgess Medical Center
🇺🇸
Kalamazoo, Michigan, United States
Allegiance Health
🇺🇸
Jackson, Michigan, United States
Saint Mary Mercy Hospital
🇺🇸
Livonia, Michigan, United States
Saint John Macomb-Oakland Hospital
🇺🇸
Warren, Michigan, United States
Saint Francis Regional Medical Center
🇺🇸
Shakopee, Minnesota, United States
Saint Luke's East - Lee's Summit
🇺🇸
Lee's Summit, Missouri, United States
Heartland Regional Medical Center
🇺🇸
Saint Joseph, Missouri, United States
Liberty Radiation Oncology Center
🇺🇸
Liberty, Missouri, United States
Saint Louis University Hospital
🇺🇸
Saint Louis, Missouri, United States
Cancer Research for the Ozarks NCORP
🇺🇸
Springfield, Missouri, United States
CoxHealth South Hospital
🇺🇸
Springfield, Missouri, United States
Montana Cancer Consortium CCOP
🇺🇸
Billings, Montana, United States
Frontier Cancer Center and Blood Institute-Billings
🇺🇸
Billings, Montana, United States
Bozeman Deaconess Hospital
🇺🇸
Bozeman, Montana, United States
Billings Clinic Cancer Center
🇺🇸
Billings, Montana, United States
California Pacific Medical Center-Pacific Campus
🇺🇸
San Francisco, California, United States
Abbott-Northwestern Hospital
🇺🇸
Minneapolis, Minnesota, United States
Audie L Murphy Veterans Affairs Hospital
🇺🇸
San Antonio, Texas, United States
University Hospital
🇺🇸
San Antonio, Texas, United States
Oncare Hawaii Inc-POB II
🇺🇸
Honolulu, Hawaii, United States
Saint Luke's South Hospital
🇺🇸
Overland Park, Kansas, United States
Mercy Hospital
🇺🇸
Coon Rapids, Minnesota, United States
Cancer Center of Kansas - Fort Scott
🇺🇸
Fort Scott, Kansas, United States
Cancer Center of Kansas - Wellington
🇺🇸
Wellington, Kansas, United States
Metro-Minnesota NCI Community Oncology Research Program
🇺🇸
Saint Louis Park, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸
Saint Louis Park, Minnesota, United States
Cancer Center of Kansas - Pratt
🇺🇸
Pratt, Kansas, United States
Fairview Ridges Hospital
🇺🇸
Burnsville, Minnesota, United States
Ridgeview Medical Center
🇺🇸
Waconia, Minnesota, United States
Cancer Center of Kansas - Parsons
🇺🇸
Parsons, Kansas, United States
Cancer Center of Kansas-Independence
🇺🇸
Independence, Kansas, United States
Menorah Medical Center
🇺🇸
Overland Park, Kansas, United States
Cancer Center of Kansas-Liberal
🇺🇸
Liberal, Kansas, United States
Cancer Center of Kansas - Dodge City
🇺🇸
Dodge City, Kansas, United States
Cancer Center of Kansas - El Dorado
🇺🇸
El Dorado, Kansas, United States
Cancer Center of Kansas-Kingman
🇺🇸
Kingman, Kansas, United States
Kansas City CCOP
🇺🇸
Prairie Village, Kansas, United States
Cancer Center of Kansas - Winfield
🇺🇸
Winfield, Kansas, United States
New Ulm Medical Center
🇺🇸
New Ulm, Minnesota, United States
Regions Hospital
🇺🇸
Saint Paul, Minnesota, United States
Associates In Womens Health
🇺🇸
Wichita, Kansas, United States
Via Christi Regional Medical Center
🇺🇸
Wichita, Kansas, United States
Wichita CCOP
🇺🇸
Wichita, Kansas, United States
Fairview-Southdale Hospital
🇺🇸
Edina, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸
Maplewood, Minnesota, United States
Lawrence Memorial Hospital
🇺🇸
Lawrence, Kansas, United States
Cancer Center of Kansas - Salina
🇺🇸
Salina, Kansas, United States
Cancer Center of Kansas - Chanute
🇺🇸
Chanute, Kansas, United States
Rice Memorial Hospital
🇺🇸
Willmar, Minnesota, United States
Cancer Center of Kansas-Wichita Medical Arts Tower
🇺🇸
Wichita, Kansas, United States
Cancer Center of Kansas - Main Office
🇺🇸
Wichita, Kansas, United States
Saint John's Hospital - Healtheast
🇺🇸
Maplewood, Minnesota, United States
Unity Hospital
🇺🇸
Fridley, Minnesota, United States
Hutchinson Area Health Care
🇺🇸
Hutchinson, Minnesota, United States
North Memorial Medical Health Center
🇺🇸
Robbinsdale, Minnesota, United States
Hennepin County Medical Center
🇺🇸
Minneapolis, Minnesota, United States
Lakeview Hospital
🇺🇸
Stillwater, Minnesota, United States
Castle Medical Center
🇺🇸
Kailua, Hawaii, United States
Oncare Hawaii Inc-Pali Momi
🇺🇸
Aiea, Hawaii, United States
Wilcox Memorial Hospital and Kauai Medical Clinic
🇺🇸
Lihue, Hawaii, United States
Pali Momi Medical Center
🇺🇸
Aiea, Hawaii, United States
Louisiana State University Health Sciences Center Shreveport
🇺🇸
Shreveport, Louisiana, United States
The University of Arizona Medical Center-University Campus
🇺🇸
Tucson, Arizona, United States
Oakwood Hospital and Medical Center
🇺🇸
Dearborn, Michigan, United States
Union Hospital of Cecil County
🇺🇸
Elkton MD, Maryland, United States
Christiana Care Health System-Christiana Hospital
🇺🇸
Newark, Delaware, United States
Hematology/Oncology Clinic LLP
🇺🇸
Baton Rouge, Louisiana, United States
Genesys Hurley Cancer Institute
🇺🇸
Flint, Michigan, United States
The University of Arizona Cancer Center-Orange Grove Campus
🇺🇸
Tucson, Arizona, United States
Saint Francis Hospital and Medical Center
🇺🇸
Hartford, Connecticut, United States
The University of Arizona Cancer Center-North Campus
🇺🇸
Tucson, Arizona, United States
Saint Joseph Mercy Port Huron
🇺🇸
Port Huron, Michigan, United States
Saint Alphonsus Cancer Care Center-Boise
🇺🇸
Boise, Idaho, United States
Bronson Methodist Hospital
🇺🇸
Kalamazoo, Michigan, United States
Saint Vincent Healthcare
🇺🇸
Billings, Montana, United States
Saint Joseph Mercy Oakland
🇺🇸
Pontiac, Michigan, United States
University of Massachusetts Medical School
🇺🇸
Worcester, Massachusetts, United States
MedStar Georgetown University Hospital
🇺🇸
Washington, District of Columbia, United States
West Michigan Cancer Center
🇺🇸
Kalamazoo, Michigan, United States
Genesys Regional Medical Center
🇺🇸
Grand Blanc, Michigan, United States
Bozeman Deaconess Cancer Center
🇺🇸
Bozeman, Montana, United States
Saint Mary's of Michigan
🇺🇸
Saginaw, Michigan, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Saint John Hospital and Medical Center
🇺🇸
Detroit, Michigan, United States
Cooper Hospital University Medical Center
🇺🇸
Camden, New Jersey, United States
Saint James Community Hospital and Cancer Treatment Center
🇺🇸
Butte, Montana, United States
Big Sky Oncology
🇺🇸
Great Falls, Montana, United States
Glacier Oncology PLLC
🇺🇸
Kalispell, Montana, United States
Kalispell Regional Medical Center
🇺🇸
Kalispell, Montana, United States
Montana Cancer Specialists
🇺🇸
Missoula, Montana, United States
Benefis Healthcare- Sletten Cancer Institute
🇺🇸
Great Falls, Montana, United States
University of Rochester
🇺🇸
Rochester, New York, United States
Northern Montana Hospital
🇺🇸
Havre, Montana, United States
Saint Peter's Community Hospital
🇺🇸
Helena, Montana, United States
Great Falls Clinic
🇺🇸
Great Falls, Montana, United States
Kalispell Medical Oncology
🇺🇸
Kalispell, Montana, United States
Weill Medical College of Cornell University
🇺🇸
New York, New York, United States
Avera Cancer Institute
🇺🇸
Sioux Falls, South Dakota, United States
Saint Alexius Medical Center
🇺🇸
Bismarck, North Dakota, United States
Laura and Issac Perlmutter Cancer Center at NYU Langone
🇺🇸
New York, New York, United States
Iredell Memorial Hospital
🇺🇸
Statesville, North Carolina, United States
Mid Dakota Clinic
🇺🇸
Bismarck, North Dakota, United States
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
🇺🇸
San Antonio, Texas, United States
Salem Hospital
🇺🇸
Salem, Oregon, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸
New York, New York, United States
BCCA-Vancouver Cancer Centre
🇨🇦
Vancouver, British Columbia, Canada
Welch Cancer Center
🇺🇸
Sheridan, Wyoming, United States
Sanford Bismarck Medical Center
🇺🇸
Bismarck, North Dakota, United States
Lehigh Valley Hospital-Cedar Crest
🇺🇸
Allentown, Pennsylvania, United States
University of Texas Health Science Center at San Antonio
🇺🇸
San Antonio, Texas, United States
Rocky Mountain Oncology
🇺🇸
Casper, Wyoming, United States
UW Cancer Center Johnson Creek
🇺🇸
Johnson Creek, Wisconsin, United States
Cancer Center of Western Wisconsin
🇺🇸
New Richmond, Wisconsin, United States
Saint Joseph Mercy Hospital
🇺🇸
Ann Arbor, Michigan, United States
Michigan Cancer Research Consortium CCOP
🇺🇸
Ann Arbor, Michigan, United States
Oncare Hawaii Inc-Kuakini
🇺🇸
Honolulu, Hawaii, United States
Kuakini Medical Center
🇺🇸
Honolulu, Hawaii, United States
Kapiolani Medical Center for Women and Children
🇺🇸
Honolulu, Hawaii, United States
Tulane University Health Sciences Center
🇺🇸
New Orleans, Louisiana, United States
Saint Luke's Cancer Institute
🇺🇸
Kansas City, Missouri, United States
Saint Luke's Hospital of Kansas City
🇺🇸
Kansas City, Missouri, United States
Saint Joseph Health Center
🇺🇸
Kansas City, Missouri, United States
North Kansas City Hospital
🇺🇸
Kansas City, Missouri, United States
Heartland Hematology and Oncology Associates Incorporated
🇺🇸
Kansas City, Missouri, United States
Research Medical Center
🇺🇸
Kansas City, Missouri, United States
University of Wisconsin Hospital and Clinics
🇺🇸
Madison, Wisconsin, United States
Mills - Peninsula Hospitals
🇺🇸
Burlingame, California, United States
Beebe Medical Center
🇺🇸
Lewes, Delaware, United States