Non Hodgkin Lymphoma Clinical Trial
Alisertib in Treating Patients With Relapsed or Refractory Peripheral T-Cell Non-Hodgkin Lymphoma
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.
Full 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
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There are 132 Locations for this study
Mobile Alabama, 36608, United States
Tucson Arizona, 85704, United States
Tucson Arizona, 85719, United States
Tucson Arizona, 85724, United States
Berkeley California, 94704, United States
Burlingame California, 94010, United States
Duarte California, 91010, United States
Novato California, 94945, United States
San Francisco California, 94118, United States
Santa Rosa California, 95403, United States
Vallejo California, 94589, United States
Hartford Connecticut, 06105, United States
Lewes Delaware, 19958, United States
Newark Delaware, 19718, United States
Washington District of Columbia, 20007, United States
Atlanta Georgia, 30322, United States
Aiea Hawaii, 96701, United States
Aiea Hawaii, 96701, United States
Honolulu Hawaii, 96813, United States
Honolulu Hawaii, 96813, United States
Honolulu Hawaii, 96813, United States
Honolulu Hawaii, 96813, United States
Honolulu Hawaii, 96817, United States
Honolulu Hawaii, 96817, United States
Honolulu Hawaii, 96817, United States
Honolulu Hawaii, 96826, United States
Kailua Hawaii, 96734, United States
Lihue Hawaii, 96766, United States
Boise Idaho, 83706, United States
Chicago Illinois, 60611, United States
Chicago Illinois, 60611, United States
Highland Park Illinois, 60035, United States
Kankakee Illinois, 60901, United States
Libertyville Illinois, 60048, United States
Maywood Illinois, 60153, United States
Niles Illinois, 60714, United States
Skokie Illinois, 60076, United States
Ames Iowa, 50010, United States
Ottumwa Iowa, 52501, United States
Chanute Kansas, 66720, United States
Dodge City Kansas, 67801, United States
El Dorado Kansas, 67042, United States
Fort Scott Kansas, 66701, United States
Independence Kansas, 67301, United States
Kingman Kansas, 67068, United States
Lawrence Kansas, 66044, United States
Liberal Kansas, 67901, United States
McPherson Kansas, 67460, United States
Newton Kansas, 67114, United States
Overland Park Kansas, 66209, United States
Overland Park Kansas, 66213, United States
Parsons Kansas, 67357, United States
Prairie Village Kansas, 66208, United States
Pratt Kansas, 67124, United States
Salina Kansas, 67401, United States
Wellington Kansas, 67152, United States
Wichita Kansas, 67208, United States
Wichita Kansas, 67208, United States
Wichita Kansas, 67214, United States
Wichita Kansas, 67214, United States
Wichita Kansas, 67214, United States
Winfield Kansas, 67156, United States
Baton Rouge Louisiana, 70809, United States
New Orleans Louisiana, 70112, United States
Shreveport Louisiana, 71103, United States
Elkton MD Maryland, 21921, United States
Worcester Massachusetts, 01655, United States
Ann Arbor Michigan, 48106, United States
Ann Arbor Michigan, 48106, United States
Dearborn Michigan, 48124, United States
Detroit Michigan, 48236, United States
Flint Michigan, 48502, United States
Flint Michigan, 48503, United States
Flint Michigan, 48532, United States
Grand Blanc Michigan, 48439, United States
Jackson Michigan, 49201, United States
Kalamazoo Michigan, 49001, United States
Kalamazoo Michigan, 49007, United States
Kalamazoo Michigan, 49007, United States
Lansing Michigan, 48912, United States
Livonia Michigan, 48154, United States
Pontiac Michigan, 48341, United States
Port Huron Michigan, 48060, United States
Saginaw Michigan, 48601, United States
Warren Michigan, 48093, United States
Burnsville Minnesota, 55337, United States
Coon Rapids Minnesota, 55433, United States
Edina Minnesota, 55435, United States
Fridley Minnesota, 55432, United States
Hutchinson Minnesota, 55350, United States
Maplewood Minnesota, 55109, United States
Maplewood Minnesota, 55109, United States
Minneapolis Minnesota, 55407, United States
Minneapolis Minnesota, 55415, United States
New Ulm Minnesota, 56073, United States
Robbinsdale Minnesota, 55422, United States
Saint Louis Park Minnesota, 55416, United States
Saint Louis Park Minnesota, 55416, United States
Saint Paul Minnesota, 55101, United States
Saint Paul Minnesota, 55102, United States
Shakopee Minnesota, 55379, United States
Stillwater Minnesota, 55082, United States
Waconia Minnesota, 55387, United States
Willmar Minnesota, 56201, United States
Woodbury Minnesota, 55125, United States
Kansas City Missouri, 64111, United States
Kansas City Missouri, 64111, United States
Kansas City Missouri, 64114, United States
Kansas City Missouri, 64116, United States
Kansas City Missouri, 64118, United States
Kansas City Missouri, 64132, United States
Lee's Summit Missouri, 64086, United States
Liberty Missouri, 64068, United States
Saint Joseph Missouri, 64506, United States
Saint Joseph Missouri, 64507, United States
Saint Louis Missouri, 63110, United States
Saint Louis Missouri, 63110, United States
Springfield Missouri, 65804, United States
Springfield Missouri, 65804, United States
Springfield Missouri, 65807, United States
Billings Montana, 59101, United States
Billings Montana, 59101, United States
Billings Montana, 59102, United States
Billings Montana, 59107, United States
Bozeman Montana, 59715, United States
Bozeman Montana, 59715, United States
Butte Montana, 59701, United States
Great Falls Montana, 59405, United States
Great Falls Montana, 59405, United States
Great Falls Montana, 59405, United States
Havre Montana, 59501, United States
Helena Montana, 59601, United States
Kalispell Montana, 59901, United States
Kalispell Montana, 59901, United States
Kalispell Montana, 59901, United States
Missoula Montana, 59802, United States
Missoula Montana, 59802, United States
Camden New Jersey, 08103, United States
New York New York, 10016, United States
New York New York, 10065, United States
New York New York, 10065, United States
Rochester New York, 14642, United States
Statesville North Carolina, 28677, United States
Bismarck North Dakota, 58501, United States
Bismarck North Dakota, 58501, United States
Bismarck North Dakota, 58501, United States
Cincinnati Ohio, 45267, United States
Salem Oregon, 97301, United States
Allentown Pennsylvania, 18103, United States
Charleston South Carolina, 29401, United States
Sioux Falls South Dakota, 57105, United States
San Antonio Texas, 78209, United States
San Antonio Texas, 78229, United States
San Antonio Texas, 78229, United States
San Antonio Texas, 78229, United States
Johnson Creek Wisconsin, 53038, United States
Madison Wisconsin, 53792, United States
New Richmond Wisconsin, 54017, United States
Casper Wyoming, 82609, United States
Sheridan Wyoming, 82801, United States
Vancouver British Columbia, V5Z 4, Canada
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