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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01466881
• Collaborator: (none)
• Enrollment: 42
• Locations: 161
• Arm: 1
• Duration (Months): 41
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Alisertib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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.

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

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

4. 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.

5. To investigate the copy number, mutational status, expression of aurora kinase (A, B, and

1. and associated signaling pathways in PTCL utilizing tissue microarray analysis (TMA) before and after treatment with MLN8237.

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

1. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of the Aurora Kinase A Inhibitor MLN8237, in Relapsed or Refractory Peripheral T-Cell Non-Hodgkin Lymphoma
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (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.	Drug: Alisertib; Given PO; Other Names: Aurora A Kinase Inhibitor MLN8237 MLN-8237 MLN8237 ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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.

Other Outcome Measures

1. Aurora Kinase A Expression [Baseline]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Providence Hospital	Mobile	Alabama	United States	36608
2	The University of Arizona Cancer Center-Orange Grove Campus	Tucson	Arizona	United States	85704
3	The University of Arizona Cancer Center-North Campus	Tucson	Arizona	United States	85719
4	The University of Arizona Medical Center-University Campus	Tucson	Arizona	United States	85724
5	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California	United States	94704
6	Mills - Peninsula Hospitals	Burlingame	California	United States	94010
7	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
8	Sutter Cancer Research Consortium	Novato	California	United States	94945
9	California Pacific Medical Center-Pacific Campus	San Francisco	California	United States	94118
10	Sutter Pacific Medical Foundation	Santa Rosa	California	United States	95403
11	Sutter Solano Medical Center/Cancer Center	Vallejo	California	United States	94589
12	Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
13	Beebe Medical Center	Lewes	Delaware	United States	19958
14	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
15	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
16	Emory University/Winship Cancer Institute	Atlanta	Georgia	United States	30322
17	Oncare Hawaii Inc-Pali Momi	Aiea	Hawaii	United States	96701
18	Pali Momi Medical Center	Aiea	Hawaii	United States	96701
19	Oncare Hawaii Inc-POB II	Honolulu	Hawaii	United States	96813
20	Queen's Medical Center	Honolulu	Hawaii	United States	96813
21	Straub Clinic and Hospital	Honolulu	Hawaii	United States	96813
22	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
23	OnCare Hawaii-Liliha	Honolulu	Hawaii	United States	96817-3169
24	Kuakini Medical Center	Honolulu	Hawaii	United States	96817
25	Oncare Hawaii Inc-Kuakini	Honolulu	Hawaii	United States	96817
26	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
27	Castle Medical Center	Kailua	Hawaii	United States	96734
28	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii	United States	96766
29	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
30	Hematology and Oncology Associates	Chicago	Illinois	United States	60611
31	Northwestern University	Chicago	Illinois	United States	60611
32	Hematology Oncology Associates of Illinois-Highland Park	Highland Park	Illinois	United States	60035
33	Presence Saint Mary's Hospital	Kankakee	Illinois	United States	60901
34	North Shore Hematology Oncology	Libertyville	Illinois	United States	60048
35	Loyola University Medical Center	Maywood	Illinois	United States	60153
36	Illinois Cancer Specialists-Niles	Niles	Illinois	United States	60714
37	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois	United States	60076
38	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa	United States	50010
39	Ottumwa Regional Health Center	Ottumwa	Iowa	United States	52501
40	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
41	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
42	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
43	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
44	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
45	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
46	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
47	Cancer Center of Kansas-Liberal	Liberal	Kansas	United States	67901
48	Cancer Center of Kansas - McPherson	McPherson	Kansas	United States	67460
49	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
50	Menorah Medical Center	Overland Park	Kansas	United States	66209
51	Saint Luke's South Hospital	Overland Park	Kansas	United States	66213
52	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
53	Kansas City CCOP	Prairie Village	Kansas	United States	66208
54	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
55	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
56	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
57	Associates In Womens Health	Wichita	Kansas	United States	67208
58	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
59	Cancer Center of Kansas - Main Office	Wichita	Kansas	United States	67214
60	Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
61	Wichita CCOP	Wichita	Kansas	United States	67214
62	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
63	Hematology/Oncology Clinic LLP	Baton Rouge	Louisiana	United States	70809
64	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
65	Louisiana State University Health Sciences Center Shreveport	Shreveport	Louisiana	United States	71103
66	Union Hospital of Cecil County	Elkton MD	Maryland	United States	21921
67	University of Massachusetts Medical School	Worcester	Massachusetts	United States	01655
68	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
69	Michigan Cancer Research Consortium CCOP	Ann Arbor	Michigan	United States	48106
70	Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48124
71	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
72	Hurley Medical Center	Flint	Michigan	United States	48502
73	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
74	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan	United States	48532
75	Genesys Regional Medical Center	Grand Blanc	Michigan	United States	48439
76	Allegiance Health	Jackson	Michigan	United States	49201
77	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
78	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
79	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
80	Sparrow Hospital	Lansing	Michigan	United States	48912
81	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
82	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
83	Saint Joseph Mercy Port Huron	Port Huron	Michigan	United States	48060
84	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
85	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
86	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
87	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
88	Fairview-Southdale Hospital	Edina	Minnesota	United States	55435
89	Unity Hospital	Fridley	Minnesota	United States	55432
90	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
91	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
92	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
93	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
94	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
95	New Ulm Medical Center	New Ulm	Minnesota	United States	56073
96	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
97	Metro-Minnesota NCI Community Oncology Research Program	Saint Louis Park	Minnesota	United States	55416
98	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
99	Regions Hospital	Saint Paul	Minnesota	United States	55101
100	United Hospital	Saint Paul	Minnesota	United States	55102
101	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
102	Lakeview Hospital	Stillwater	Minnesota	United States	55082
103	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
104	Rice Memorial Hospital	Willmar	Minnesota	United States	56201
105	Minnesota Oncology and Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
106	Saint Luke's Cancer Institute	Kansas City	Missouri	United States	64111
107	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
108	Saint Joseph Health Center	Kansas City	Missouri	United States	64114
109	North Kansas City Hospital	Kansas City	Missouri	United States	64116
110	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri	United States	64118
111	Research Medical Center	Kansas City	Missouri	United States	64132
112	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
113	Liberty Radiation Oncology Center	Liberty	Missouri	United States	64068
114	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
115	Saint Joseph Oncology Inc	Saint Joseph	Missouri	United States	64507
116	Saint Louis University Hospital	Saint Louis	Missouri	United States	63110
117	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
118	Cancer Research for the Ozarks NCORP	Springfield	Missouri	United States	65804
119	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
120	CoxHealth South Hospital	Springfield	Missouri	United States	65807
121	Montana Cancer Consortium CCOP	Billings	Montana	United States	59101
122	Saint Vincent Healthcare	Billings	Montana	United States	59101
123	Frontier Cancer Center and Blood Institute-Billings	Billings	Montana	United States	59102
124	Billings Clinic Cancer Center	Billings	Montana	United States	59107
125	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
126	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
127	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
128	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
129	Big Sky Oncology	Great Falls	Montana	United States	59405
130	Great Falls Clinic	Great Falls	Montana	United States	59405
131	Northern Montana Hospital	Havre	Montana	United States	59501
132	Saint Peter's Community Hospital	Helena	Montana	United States	59601
133	Glacier Oncology PLLC	Kalispell	Montana	United States	59901
134	Kalispell Medical Oncology	Kalispell	Montana	United States	59901
135	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
136	Montana Cancer Specialists	Missoula	Montana	United States	59802
137	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
138	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
139	Laura and Issac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
140	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
141	Weill Medical College of Cornell University	New York	New York	United States	10065
142	University of Rochester	Rochester	New York	United States	14642
143	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
144	Mid Dakota Clinic	Bismarck	North Dakota	United States	58501
145	Saint Alexius Medical Center	Bismarck	North Dakota	United States	58501
146	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
147	University of Cincinnati	Cincinnati	Ohio	United States	45267
148	Salem Hospital	Salem	Oregon	United States	97301
149	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
150	Roper Hospital	Charleston	South Carolina	United States	29401
151	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
152	Audie L Murphy Veterans Affairs Hospital	San Antonio	Texas	United States	78209
153	Cancer Therapy and Research Center at The UT Health Science Center at San Antonio	San Antonio	Texas	United States	78229
154	University Hospital	San Antonio	Texas	United States	78229
155	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
156	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin	United States	53038
157	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
158	Cancer Center of Western Wisconsin	New Richmond	Wisconsin	United States	54017
159	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
160	Welch Cancer Center	Sheridan	Wyoming	United States	82801
161	BCCA-Vancouver Cancer Centre	Vancouver	British Columbia	Canada	V5Z 4E6

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Paul Barr, Southwest Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01466881
• Other Study ID Numbers: NCI-2011-03551; NCI-2011-03551; SWOG-S1108; CDR0000714328; S1108; S1108; U10CA180888; U10CA032102
• First Posted: Nov 8, 2011
• Last Update Posted: Mar 10, 2016
• Last Verified: Jan 1, 2015

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Leukemia, T-Cell; Leukemia-Lymphoma, Adult T-Cell; Lymphoma, Large-Cell, Anaplastic; Lymphoma, Extranodal NK-T-Cell; Immunoblastic Lymphadenopathy; Recurrence

Study Results

Participant Flow

Arm/Group Title	MLN8237
Arm/Group Description	Patients receive MLN8237 (alisertib) PO BID on days 1-7. Treatment repeats every 21 days for 17 courses in the absence of disease progression or unacceptable toxicity
Period Title: Overall Study
STARTED	42
Eligible and Treated	37
COMPLETED	2
NOT COMPLETED	40

Baseline Characteristics

Arm/Group Title	MLN8237
Arm/Group Description	Patients receive MLN8237 (alisertib) PO BID on days 1-7. Treatment repeats every 21 days for 17 courses in the absence of disease progression or unacceptable toxicity
Overall Participants	37
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62.0
Sex: Female, Male (Count of Participants)
Female	13 35.1%
Male	24 64.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 10.8%
Not Hispanic or Latino	32 86.5%
Unknown or Not Reported	1 2.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 2.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	10 27%
White	24 64.9%
More than one race	0 0%
Unknown or Not Reported	2 5.4%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (Complete Responses (CR) + Partial Responses (PR))
Description	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.
Time Frame	Up to 1 year after registration

Outcome Measure Data

Analysis Population Description

All eligible patients who started treatment were included in assessing response estimates.

Arm/Group Title	MLN8237
Arm/Group Description	Patients receive MLN8237 (alisertib) PO BID on days 1-7. Treatment repeats every 21 days for 17 courses in the absence of disease progression or unacceptable toxicity
Measure Participants	37
Complete Response	2 5.4%
Partial Response	7 18.9%
No response	28 75.7%

2. Secondary Outcome

Title	Overall Survival (OS)
Description	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.
Time Frame	Up to 2 years after registration

Outcome Measure Data

Analysis Population Description

Only eligible patients were included in the analysis.

Arm/Group Title	MLN8237
Arm/Group Description	Patients receive MLN8237 (alisertib) PO BID on days 1-7. Treatment repeats every 21 days for 17 courses in the absence of disease progression or unacceptable toxicity
Measure Participants	37
Median (95% Confidence Interval) [Months]	8

3. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	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.
Time Frame	Up to 2 years after registration

Outcome Measure Data

Analysis Population Description

Only eligible patients were included in the analysis

Arm/Group Title	MLN8237
Arm/Group Description	Patients receive MLN8237 (alisertib) PO BID on days 1-7. Treatment repeats every 21 days for 17 courses in the absence of disease progression or unacceptable toxicity
Measure Participants	37
Mean (95% Confidence Interval) [Months]	3

4. Secondary Outcome

Title	To Evaluate the Safety and Tolerability of MLN8237 (Number of With Grade 3 Through Grade 5 Adverse Events That Are Related to MLN8237)
Description	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.
Time Frame	Up to 1 year after registration

Outcome Measure Data

Analysis Population Description

Eligible patients who had received any treatment were included in the adverse event summaries. Any CTCAE 4.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which deemed to be related to protocol treatment are included.

Arm/Group Title	MLN8237
Arm/Group Description	Patients receive MLN8237 (alisertib) PO BID on days 1-7. Treatment repeats every 21 days for 17 courses in the absence of disease progression or unacceptable toxicity
Measure Participants	37
Abdominal pain	1 2.7%
Alkaline phosphatase increased	2 5.4%
Anemia	12 32.4%
Anorexia	1 2.7%
Back pain	1 2.7%
Blood bilirubin increased	1 2.7%
CD4 lymphocytes decreased	2 5.4%
Diarrhea	1 2.7%
Fatigue	1 2.7%
Febrile neutropenia	5 13.5%
Fever	1 2.7%
Gastrointestinal disorders - Other, specify	1 2.7%
Hypercalcemia	1 2.7%
Hyperglycemia	1 2.7%
Hypotension	1 2.7%
Infections and infestations - Other, specify	1 2.7%
Leukocytosis	1 2.7%
Lung infection	1 2.7%
Lymph gland infection	1 2.7%
Lymphocyte count decreased	8 21.6%
Mucositis oral	4 10.8%
Neutrophil count decreased	12 32.4%
Pain	2 5.4%
Platelet count decreased	9 24.3%
Rash maculo-papular	2 5.4%
Sepsis	1 2.7%
Skin and subcutaneous tissue disorders - Other	1 2.7%
Skin infection	1 2.7%
Toxic epidermal necrolysis	1 2.7%
Treatment related secondary malignancy	1 2.7%
White blood cell decreased	7 18.9%

5. Other Pre-specified Outcome

Title	Aurora Kinase A Expression
Description	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
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Eligible patients who consented for correlative studies and had Aurora kinase A expression measured.

Arm/Group Title	Non-responders	Responders
Arm/Group Description	Eligible patients who received protocol treatment and did not respond to the protocol treatment. Patients for whom response assessment was inadequate were considered non-responders.	Eligible Patients who received protocol treatment and achieved complete or partial response.
Measure Participants	19	3
Mean (Standard Deviation) [proportion of positivity]	0.121 (0.096)	0.063 (0.060)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MLN8237, Responders
	Comments	The null hypothesis is that there is no significant difference in Aurora kinase A expression between responders and non-responders.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2316
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments	Two-sided alpha level of 0.05

Adverse Events

Time Frame	Up to 1 year after registration
Adverse Event Reporting Description	Eligible patients who had received any treatment were included. Incidence of toxicity as assessed by the Common Terminology Criteria for Adverse Events version 4.0.
Arm/Group Title	MLN8237
Arm/Group Description	Patients receive MLN8237 (alisertib) PO BID on days 1-7. Treatment repeats every 21 days for 17 courses in the absence of disease progression or unacceptable toxicity
All Cause Mortality
	MLN8237
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	MLN8237
	Affected / at Risk (%)	# Events
Total	19/37 (51.4%)
Blood and lymphatic system disorders
Anemia	1/37 (2.7%)
Febrile neutropenia	2/37 (5.4%)
Cardiac disorders
Cardiac disorders-Other	1/37 (2.7%)
Heart failure	1/37 (2.7%)
Supraventricular tachycardia	1/37 (2.7%)
Gastrointestinal disorders
Diarrhea	1/37 (2.7%)
Gastrointestinal disorders-Other	1/37 (2.7%)
Mucositis oral	1/37 (2.7%)
General disorders
Multi-organ failure	1/37 (2.7%)
Infections and infestations
Lung infection	1/37 (2.7%)
Lymph gland infection	1/37 (2.7%)
Sepsis	1/37 (2.7%)
Skin infection	1/37 (2.7%)
Investigations
Alanine aminotransferase increased	1/37 (2.7%)
Blood bilirubin increased	1/37 (2.7%)
Neutrophil count decreased	1/37 (2.7%)
Platelet count decreased	2/37 (5.4%)
Metabolism and nutrition disorders
Hypercalcemia	1/37 (2.7%)
Musculoskeletal and connective tissue disorders
Flank pain	1/37 (2.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified - Other	2/37 (5.4%)
Treatment related secondary malignancy	1/37 (2.7%)
Nervous system disorders
Encephalopathy	1/37 (2.7%)
Facial nerve disorder	1/37 (2.7%)
Seizure	1/37 (2.7%)
Renal and urinary disorders
Acute kidney injury	1/37 (2.7%)
Renal and urinary disorders-Other	1/37 (2.7%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/37 (2.7%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/37 (2.7%)
Skin and subcutaneous tissue disorders - Other	1/37 (2.7%)
Toxic epidermal necrolysis	1/37 (2.7%)
Vascular disorders
Hypotension	2/37 (5.4%)
Thromboembolic event	1/37 (2.7%)
Other (Not Including Serious) Adverse Events
	MLN8237
	Affected / at Risk (%)	# Events
Total	36/37 (97.3%)
Blood and lymphatic system disorders
Anemia	23/37 (62.2%)
Blood and lymphatic system disorders - Other	2/37 (5.4%)
Febrile neutropenia	4/37 (10.8%)
Cardiac disorders
Sinus tachycardia	2/37 (5.4%)
Gastrointestinal disorders
Abdominal pain	4/37 (10.8%)
Constipation	8/37 (21.6%)
Diarrhea	12/37 (32.4%)
Dysphagia	2/37 (5.4%)
Mucositis oral	7/37 (18.9%)
Nausea	7/37 (18.9%)
Oral pain	2/37 (5.4%)
Rectal hemorrhage	2/37 (5.4%)
Vomiting	6/37 (16.2%)
General disorders
Chills	2/37 (5.4%)
Edema limbs	8/37 (21.6%)
Fatigue	23/37 (62.2%)
Fever	11/37 (29.7%)
Pain	9/37 (24.3%)
Infections and infestations
Infections and infestations-Other	2/37 (5.4%)
Sinusitis	2/37 (5.4%)
Skin infection	2/37 (5.4%)
Upper respiratory infection	2/37 (5.4%)
Urinary tract infection	2/37 (5.4%)
Injury, poisoning and procedural complications
Fall	2/37 (5.4%)
Investigations
Alanine aminotransferase increased	5/37 (13.5%)
Alkaline phosphatase increased	8/37 (21.6%)
Aspartate aminotransferase increased	7/37 (18.9%)
Blood bilirubin increased	4/37 (10.8%)
CD4 lymphocytes decreased	2/37 (5.4%)
Creatinine increased	7/37 (18.9%)
Lymphocyte count decreased	14/37 (37.8%)
Neutrophil count decreased	15/37 (40.5%)
Platelet count decreased	19/37 (51.4%)
Weight loss	4/37 (10.8%)
White blood cell decreased	15/37 (40.5%)
Metabolism and nutrition disorders
Anorexia	8/37 (21.6%)
Dehydration	4/37 (10.8%)
Hypercalcemia	2/37 (5.4%)
Hyperglycemia	2/37 (5.4%)
Hypernatremia	2/37 (5.4%)
Hyperuricemia	2/37 (5.4%)
Hypoalbuminemia	9/37 (24.3%)
Hypocalcemia	7/37 (18.9%)
Hypoglycemia	2/37 (5.4%)
Hypokalemia	2/37 (5.4%)
Hyponatremia	9/37 (24.3%)
Musculoskeletal and connective tissue disorders
Back pain	5/37 (13.5%)
Pain in extremity	3/37 (8.1%)
Nervous system disorders
Headache	4/37 (10.8%)
Memory impairment	2/37 (5.4%)
Peripheral sensory neuropathy	2/37 (5.4%)
Somnolence	2/37 (5.4%)
Psychiatric disorders
Anxiety	2/37 (5.4%)
Insomnia	3/37 (8.1%)
Respiratory, thoracic and mediastinal disorders
Cough	5/37 (13.5%)
Dyspnea	3/37 (8.1%)
Nasal congestion	2/37 (5.4%)
Productive cough	3/37 (8.1%)
Skin and subcutaneous tissue disorders
Alopecia	9/37 (24.3%)
Pruritus	4/37 (10.8%)
Rash maculo-papular	5/37 (13.5%)
Skin and subcutaneous tissue disorders - Other	4/37 (10.8%)
Skin hyperpigmentation	2/37 (5.4%)
Skin ulceration	2/37 (5.4%)
Vascular disorders
Hypertension	2/37 (5.4%)
Hypotension	3/37 (8.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.