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

Anaplastic Large Cell Lymphoma Clinical Trial

Official title:

Phase II Trial of the Aurora Kinase A Inhibitor MLN8237, in Relapsed or Refractory Peripheral T-Cell Non-Hodgkin Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01466881
• Other study ID #: NCI-2011-03551
• Secondary ID: NCI-2011-03551SW
• Status: Completed
• Phase: Phase 2
• First received: November 3, 2011
• Last updated: February 9, 2016
• Start date: October 2011
• Est. completion date: March 2015

Study information

• Verified date: January 2015
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: March 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Alisertib
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Pharmacological Study
Correlative studies

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Aurora Kinase A Expression	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 PTCL treated with MLN8237	Baseline	No
Primary	Objective Response Rate (Complete Responses (CR) + Partial Responses (PR))	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.	Up to 1 year after registration	No
Secondary	Overall Survival (OS)	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.	Up to 2 years after registration	No
Secondary	Progression Free Survival (PFS)	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.	Up to 2 years after registration	No
Secondary	To Evaluate the Safety and Tolerability of MLN8237 (Number of With Grade 3 Through Grade 5 Adverse Events That Are Related to MLN8237)	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.	Up to 1 year after registration	Yes