ClinicalTrials.gov
ClinicalTrials.gov Menu

Alisertib (MLN8237) or Investigator's Choice in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01482962
Recruitment Status : Completed
First Posted : December 1, 2011
Results First Posted : July 31, 2018
Last Update Posted : July 31, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Relapsed Peripheral T-Cell Lymphoma
Refractory Peripheral T-Cell Lymphoma
Interventions Drug: Alisertib
Drug: Pralatrexate
Drug: Gemcitabine
Drug: Romidepsin
Enrollment 271
Recruitment Details Participants took part in the study at 105 investigative sites in the United States including Puerto Rico, Canada, European Union, Russian Federation, Turkey, Israel, Australia, New Zealand and Latin America from 11 June 2012 to the end of study on 18 December 2017.
Pre-assignment Details Participants with a diagnosis of Relapsed or Refractory Peripheral T-Cell Lymphoma were randomized 1:1 to either alisertib or comparator (investigator’s choice of pralatrexate, romidepsin [USA only], or gemcitabine).
Arm/Group Title Alisertib Pralatrexate, or Romidepsin, or Gemcitabine
Hide Arm/Group Description Alisertib 50 mg, enteric-coated tablet formulation, orally, twice daily for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle (Up to 148 Weeks). Pralatrexate 30 mg/m^2, intravenous (IV) push over 3 to 5 minutes, once weekly, for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles were repeated every 7-weeks provided the participant continued to benefit from and tolerate the therapy (Up to 115 Weeks), or Gemcitabine 1,000 mg/m^2 over 30 minutes, intravenously, on Days 1, 8, and 15 of a 28-day cycle until the absence of disease progression or unacceptable toxicity (Up to 32 Weeks), or Romidepsin 14 mg/m^2, intravenously over a 4-hour period, on Days 1, 8, and 15 of a 28-cycle. Cycles were repeated every 28 days provided the patient continued to benefit from and tolerate the therapy (Up to 30 Weeks).
Period Title: Overall Study
Started 138 133
Safety Population: Received Study Drug 137 127
Completed 0 0
Not Completed 138 133
Reason Not Completed
Progressive Disease             65             53
Unsatisfactory Therapeutic Response             37             23
Adverse Event             18             22
Withdrawal by Participant             8             13
Hematopoietic Stem Cell Transplant             3             9
Other Reason             1             5
Study Terminated by Sponsor             5             2
Did not Receive Study Drug             1             6
Arm/Group Title Alisertib Pralatrexate, or Romidepsin, or Gemcitabine Total
Hide Arm/Group Description Alisertib 50 mg, enteric-coated tablet formulation, orally, twice daily for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle (Up to 148 Weeks). Pralatrexate 30 mg/m^2, intravenous (IV) push over 3 to 5 minutes, once weekly, for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles were repeated every 7-weeks provided the participant continued to benefit from and tolerate the therapy (Up to 115 Weeks), or Gemcitabine 1,000 mg/m^2 over 30 minutes, intravenously, on Days 1, 8, and 15 of a 28-day cycle until the absence of disease progression or unacceptable toxicity (Up to 32 Weeks), or Romidepsin 14 mg/m^2, intravenously over a 4-hour period, on Days 1, 8, and 15 of a 28-cycle. Cycles were repeated every 28 days provided the patient continued to benefit from and tolerate the therapy (Up to 30 Weeks). Total of all reporting groups
Overall Number of Baseline Participants 138 133 271
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population was defined as all participants who were randomized. The participants were analyzed according to the treatment they were randomized to receive, regardless of any errors of dosing.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 138 participants 133 participants 271 participants
61.1  (12.69) 61.4  (13.16) 61.3  (12.90)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 138 participants 133 participants 271 participants
Female
46
  33.3%
47
  35.3%
93
  34.3%
Male
92
  66.7%
86
  64.7%
178
  65.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 138 participants 133 participants 271 participants
Hispanic or Latino
25
  18.1%
21
  15.8%
46
  17.0%
Not Hispanic or Latino
105
  76.1%
107
  80.5%
212
  78.2%
Unknown or Not Reported
8
   5.8%
5
   3.8%
13
   4.8%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 138 participants 133 participants 271 participants
White 115 114 229
Black or African American 8 8 16
Asian 3 2 5
Other 7 7 14
Not Reported 5 2 7
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 138 participants 133 participants 271 participants
Australia 5 4 9
Austria 2 2 4
Belgium 5 3 8
Brazil 12 10 22
Bulgaria 0 1 1
Canada 3 0 3
Czech Republic 5 2 7
Denmark 3 2 5
France 5 3 8
Germany 6 1 7
Hungary 9 7 16
Israel 0 3 3
Italy 6 6 12
Mexico 3 1 4
Netherlands 0 1 1
New Zealand 3 2 5
Peru 1 3 4
Poland 7 3 10
Portugal 1 1 2
Puerto Rico 0 1 1
Romania 2 1 3
Russia 4 4 8
Spain 14 11 25
Sweden 0 3 3
Turkey 10 11 21
United Kingdom 3 8 11
United States 29 39 68
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 138 participants 133 participants 271 participants
170.3  (9.80) 168.2  (8.99) 169.3  (9.45)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 138 participants 133 participants 271 participants
76.85  (17.242) 74.63  (19.601) 75.76  (18.437)
Body Surface Area (BSA)   [1] 
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 138 participants 133 participants 271 participants
1.897  (0.2465) 1.855  (0.2562) 1.877  (0.2517)
[1]
Measure Analysis Population Description: Body surface area (m^2)=square root [height (cm)*weight (kg)/3600].
1.Primary Outcome
Title Overall Response Rate (ORR) Based on Independent Review Committee (IRC) Assessment
Hide Description ORR was defined as the percentage of participants who achieve Complete Response (CR) or Partial Response (PR) as assessed by the IRC using International Working Group (IWG) criteria. CR=Disappearance of all evidence of disease and PR=Regression of measurable disease and no new sites.
Time Frame Every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until progressive disease. Duration is approximately 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Response-evaluable population, participants with peripheral T-cell lymphoma confirmed by an independent hematopathology central review, with measurable disease at Baseline, who received at least 1 dose of alisertib or comparator and had postbaseline response assessment of CR, PR, stable disease (SD) or progressive disease (PD) by the IRC.
Arm/Group Title Alisertib Pralatrexate, or Romidepsin, or Gemcitabine
Hide Arm/Group Description:
Alisertib 50 mg, enteric-coated tablet formulation, orally, twice daily for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle (Up to 148 Weeks).
Pralatrexate 30 mg/m^2, intravenous (IV) push over 3 to 5 minutes, once weekly, for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles were repeated every 7-weeks provided the participant continued to benefit from and tolerate the therapy (Up to 115 Weeks), or Gemcitabine 1,000 mg/m^2 over 30 minutes, intravenously, on Days 1, 8, and 15 of a 28-day cycle until the absence of disease progression or unacceptable toxicity (Up to 32 Weeks), or Romidepsin 14 mg/m^2, intravenously over a 4-hour period, on Days 1, 8, and 15 of a 28-cycle. Cycles were repeated every 28 days provided the patient continued to benefit from and tolerate the therapy (Up to 30 Weeks).
Overall Number of Participants Analyzed 102 92
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
33
(24 to 43)
45
(34 to 55)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib, Pralatrexate, or Romidepsin, or Gemcitabine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.038
Comments P-value was stratified using disease type, International Prognostic Index (IPI) Score and region as stratification factors.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.33 to 1.08
Estimation Comments [Not Specified]
2.Primary Outcome
Title Progression-Free Survival (PFS) Based on IRC Assessment
Hide Description PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death due to any cause, whichever occurred first.
Time Frame Every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until progressive disease. Duration is approximately 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population was defined as all participants who were randomized. The participants were analyzed according to the treatment they were randomized to receive, regardless of any errors of dosing.
Arm/Group Title Alisertib Pralatrexate, or Romidepsin, or Gemcitabine
Hide Arm/Group Description:
Alisertib 50 mg, enteric-coated tablet formulation, orally, twice daily for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle (Up to 148 Weeks).
Pralatrexate 30 mg/m^2, intravenous (IV) push over 3 to 5 minutes, once weekly, for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles were repeated every 7-weeks provided the participant continued to benefit from and tolerate the therapy (Up to 115 Weeks), or Gemcitabine 1,000 mg/m^2 over 30 minutes, intravenously, on Days 1, 8, and 15 of a 28-day cycle until the absence of disease progression or unacceptable toxicity (Up to 32 Weeks), or Romidepsin 14 mg/m^2, intravenously over a 4-hour period, on Days 1, 8, and 15 of a 28-cycle. Cycles were repeated every 28 days provided the patient continued to benefit from and tolerate the therapy (Up to 30 Weeks).
Overall Number of Participants Analyzed 138 133
Median (95% Confidence Interval)
Unit of Measure: days
115
(83 to 174)
104
(61 to 114)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib, Pralatrexate, or Romidepsin, or Gemcitabine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.177
Comments [Not Specified]
Method Stratified Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.637 to 1.178
Estimation Comments Hazard ratio (HR) was based on a stratified Cox’s proportional hazard regression model with stratification factors: disease type, IPI Score and region with treatment as a factor in the model.
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from the date of randomization to the date of death. Participants without documentation of death were censored at the date last known to be alive.
Time Frame Participants were followed for survival for 2 years from date of last participant off study treatment, or death, whichever occurs first. Contacts were every 4 months (Median follow-up 519 days in the alisertib arm and 586 days in the comparative arm)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population was defined as all participants who were randomized. The participants were analyzed according to the treatment they were randomized to receive, regardless of any errors of dosing.
Arm/Group Title Alisertib Pralatrexate, or Romidepsin, or Gemcitabine
Hide Arm/Group Description:
Alisertib 50 mg, enteric-coated tablet formulation, orally, twice daily for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle (Up to 148 Weeks).
Pralatrexate 30 mg/m^2, intravenous (IV) push over 3 to 5 minutes, once weekly, for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles were repeated every 7-weeks provided the participant continued to benefit from and tolerate the therapy (Up to 115 Weeks), or Gemcitabine 1,000 mg/m^2 over 30 minutes, intravenously, on Days 1, 8, and 15 of a 28-day cycle until the absence of disease progression or unacceptable toxicity (Up to 32 Weeks), or Romidepsin 14 mg/m^2, intravenously over a 4-hour period, on Days 1, 8, and 15 of a 28-cycle. Cycles were repeated every 28 days provided the patient continued to benefit from and tolerate the therapy (Up to 30 Weeks).
Overall Number of Participants Analyzed 138 133
Median (95% Confidence Interval)
Unit of Measure: days
415
(263 to 514)
367
(258 to 572)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib, Pralatrexate, or Romidepsin, or Gemcitabine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.338
Comments [Not Specified]
Method Stratified Log-rank Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.707 to 1.369
Estimation Comments Hazard ratio (HR) was based on a stratified Cox’s proportional hazard regression model with stratification factors: disease type, IPI Score and region with treatment as a factor in the model.
4.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Hide Description An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. A SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/ birth defect or is a medically important event.
Time Frame First dose to 30 days after last dose of study drug or comparator (Up to 152 Weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all participants who received at least 1 dose of alisertib, or one of the comparator drugs. Participants were analyzed according to the treatment actually received.
Arm/Group Title Alisertib Pralatrexate, or Romidepsin, or Gemcitabine
Hide Arm/Group Description:
Alisertib 50 mg, enteric-coated tablet formulation, orally, twice daily for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle (Up to 148 Weeks).
Pralatrexate 30 mg/m^2, intravenous (IV) push over 3 to 5 minutes, once weekly, for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles were repeated every 7-weeks provided the participant continued to benefit from and tolerate the therapy (Up to 115 Weeks), or Gemcitabine 1,000 mg/m^2 over 30 minutes, intravenously, on Days 1, 8, and 15 of a 28-day cycle until the absence of disease progression or unacceptable toxicity (Up to 32 Weeks), or Romidepsin 14 mg/m^2, intravenously over a 4-hour period, on Days 1, 8, and 15 of a 28-cycle. Cycles were repeated every 28 days provided the patient continued to benefit from and tolerate the therapy (Up to 30 Weeks).
Overall Number of Participants Analyzed 137 127
Measure Type: Number
Unit of Measure: participants
TEAE 136 126
SAE 75 69
5.Secondary Outcome
Title Number of Participants With Clinically Important Abnormal Laboratory Values Reported as AEs
Hide Description Clinical laboratory tests included chemistry, hematology and urinalysis test. Clinically significant treatment-emergent laboratory abnormalities were reported by the investigator as TEAEs.
Time Frame First dose to 30 days after last dose of study drug or comparator (Up to 152 Weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all participants who received at least 1 dose of alisertib, or one of the comparator drugs. Participants were analyzed according to the treatment actually received.
Arm/Group Title Alisertib Pralatrexate, or Romidepsin, or Gemcitabine
Hide Arm/Group Description:
Alisertib 50 mg, enteric-coated tablet formulation, orally, twice daily for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle (Up to 148 Weeks).
Pralatrexate 30 mg/m^2, intravenous (IV) push over 3 to 5 minutes, once weekly, for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles were repeated every 7-weeks provided the participant continued to benefit from and tolerate the therapy (Up to 115 Weeks), or Gemcitabine 1,000 mg/m^2 over 30 minutes, intravenously, on Days 1, 8, and 15 of a 28-day cycle until the absence of disease progression or unacceptable toxicity (Up to 32 Weeks), or Romidepsin 14 mg/m^2, intravenously over a 4-hour period, on Days 1, 8, and 15 of a 28-cycle. Cycles were repeated every 28 days provided the patient continued to benefit from and tolerate the therapy (Up to 30 Weeks).
Overall Number of Participants Analyzed 137 127
Measure Type: Number
Unit of Measure: participants
Neutrophil Count Decreased 18 14
White Blood Cell Count Decreased 17 10
Lymphocyte Count Decreased 6 5
Monocyte Count Decreased 2 1
Lymphocyte Count Increased 1 0
Monocyte Count Increased 1 0
White Blood Cell Count Increased 1 0
Platelet Count Decreased 15 22
Alanine Aminotransferase Increased 8 11
Aspartate Aminotransferase Increased 5 11
Gamma-glutamyltransferase Increased 6 3
Blood Bilirubin Increased 2 1
Hepatic Enzyme Increased 2 0
Liver Function Test Abnormal 0 1
Transaminases Increased 0 1
Blood Alkaline Phosphatase Increased 9 7
Blood Lactate Dehydrogenase Increased 5 1
Blood Creatinine Increased 3 7
Blood Creatinine Decreased 0 1
Blood Urea Increased 1 0
Blood Potassium Decreased 1 4
Blood Magnesium Decreased 1 2
Blood Bicarbonate Decreased 0 1
Blood Calcium Decreased 0 1
Blood Calcium Increased 1 0
Blood Phosphorus Decreased 0 1
Calcium Ionised Increased 1 0
Haemoglobin Decreased 1 3
Haematocrit Increased 1 2
Haematocrit Decreased 1 0
Coagulation Factor XIII Level Decreased 1 0
International Normalised Ratio Increased 1 0
Blood Albumin Decreased 0 2
Myocardial Necrosis Marker Increased 1 0
Troponin Increased 0 1
Blood Glucose Increased 0 1
Immunoglobulins Increased 1 0
Blood Uric Acid Increased 1 0
Enterovirus Test Positive 0 1
6.Secondary Outcome
Title Number of Participants With Clinically Important Vital Sign Measurements Reported as AEs
Hide Description Vital signs included blood pressure, heart rate and temperature. Individual clinically significant changes in vital signs were reported by the investigator as TEAEs.
Time Frame First dose to 30 days after last dose of study drug or comparator (Up to 152 Weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population was defined as all participants who received at least 1 dose of alisertib, or one of the comparator drugs. Participants were analyzed according to the treatment actually received.
Arm/Group Title Alisertib Pralatrexate, or Romidepsin, or Gemcitabine
Hide Arm/Group Description:
Alisertib 50 mg, enteric-coated tablet formulation, orally, twice daily for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle (Up to 148 Weeks).
Pralatrexate 30 mg/m^2, intravenous (IV) push over 3 to 5 minutes, once weekly, for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles were repeated every 7-weeks provided the participant continued to benefit from and tolerate the therapy (Up to 115 Weeks), or Gemcitabine 1,000 mg/m^2 over 30 minutes, intravenously, on Days 1, 8, and 15 of a 28-day cycle until the absence of disease progression or unacceptable toxicity (Up to 32 Weeks), or Romidepsin 14 mg/m^2, intravenously over a 4-hour period, on Days 1, 8, and 15 of a 28-cycle. Cycles were repeated every 28 days provided the patient continued to benefit from and tolerate the therapy (Up to 30 Weeks).
Overall Number of Participants Analyzed 137 127
Measure Type: Number
Unit of Measure: participants
Heart Rate Increased 1 0
Body Temperature Increased 0 1
Hypotension 4 6
Orthostatic Hypotension 2 1
Hypertension 5 7
Pyrexia 48 40
7.Secondary Outcome
Title Complete Response (CR) Rate
Hide Description Complete Response (CR) rate is defined as the percentage of participants with CR as assessed by the IRC using IWG criteria (2007 Cheson). CR= Disappearance of all evidence of disease.
Time Frame At the end of every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until PD (approximately 3 years)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Response-evaluable population was defined as participants with peripheral T-cell lymphoma confirmed by an independent hematopathology central review, with measurable disease at baseline, who receive at least 1 dose of alisertib or the comparator drug, and 1 postbaseline response assessment of CR, PR, SD or PD by the independent radiology committee.
Arm/Group Title Alisertib Pralatrexate, or Romidepsin, or Gemcitabine
Hide Arm/Group Description:
Alisertib 50 mg, enteric-coated tablet formulation, orally, twice daily for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle (Up to 148 Weeks).
Pralatrexate 30 mg/m^2, intravenous (IV) push over 3 to 5 minutes, once weekly, for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles were repeated every 7-weeks provided the participant continued to benefit from and tolerate the therapy (Up to 115 Weeks), or Gemcitabine 1,000 mg/m^2 over 30 minutes, intravenously, on Days 1, 8, and 15 of a 28-day cycle until the absence of disease progression or unacceptable toxicity (Up to 32 Weeks), or Romidepsin 14 mg/m^2, intravenously over a 4-hour period, on Days 1, 8, and 15 of a 28-cycle. Cycles were repeated every 28 days provided the patient continued to benefit from and tolerate the therapy (Up to 30 Weeks).
Overall Number of Participants Analyzed 102 92
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
18
(11 to 26)
27
(18 to 37)
8.Secondary Outcome
Title Time to Disease Progression (TTP)
Hide Description Time to Progression (TTP) was defined as the time from the date of randomization to the date of first documentation of PD/relapse.
Time Frame At the end of every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until progressive disease. Duration is approximately 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population was defined as all participants who were randomized. The participants were analyzed according to the treatment they were randomized to receive, regardless of any errors of dosing.
Arm/Group Title Alisertib Pralatrexate, or Romidepsin, or Gemcitabine
Hide Arm/Group Description:
Alisertib 50 mg, enteric-coated tablet formulation, orally, twice daily for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle (Up to 148 Weeks).
Pralatrexate 30 mg/m^2, intravenous (IV) push over 3 to 5 minutes, once weekly, for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles were repeated every 7-weeks provided the participant continued to benefit from and tolerate the therapy (Up to 115 Weeks), or Gemcitabine 1,000 mg/m^2 over 30 minutes, intravenously, on Days 1, 8, and 15 of a 28-day cycle until the absence of disease progression or unacceptable toxicity (Up to 32 Weeks), or Romidepsin 14 mg/m^2, intravenously over a 4-hour period, on Days 1, 8, and 15 of a 28-cycle. Cycles were repeated every 28 days provided the patient continued to benefit from and tolerate the therapy (Up to 30 Weeks).
Overall Number of Participants Analyzed 138 133
Median (95% Confidence Interval)
Unit of Measure: days
162
(114 to 231)
116
(101 to 227)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alisertib, Pralatrexate, or Romidepsin, or Gemcitabine
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.362
Comments [Not Specified]
Method Stratified Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.679 to 1.329
Estimation Comments Hazard ratio was based on a stratified Cox’s proportional hazard regression model with stratification factors: disease type, IPI Score and region with treatment as a factor in the model.
9.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR was defined as the time from the date of first documentation of a PR or better to the date of first documentation of progressive disease (PD)/relapse for responders as assessed by the IRC using IWG criteria. Responders without documentation of PD/relapse were censored at the date of last response assessment that was stable disease (SD) or better.
Time Frame At the end of every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until progressive disease. Duration is approximately 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All responders in response-evaluable population defined as participants with peripheral T-cell lymphoma confirmed by independent hematopathology central review with measurable disease at baseline who receive at least 1 dose of alisertib or comparator drug and 1 postbaseline response assessment of CR, PR, SD or PD by independent radiology committee.
Arm/Group Title Alisertib Pralatrexate, or Romidepsin, or Gemcitabine
Hide Arm/Group Description:
Alisertib 50 mg, enteric-coated tablet formulation, orally, twice daily for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle (Up to 148 Weeks).
Pralatrexate 30 mg/m^2, intravenous (IV) push over 3 to 5 minutes, once weekly, for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles were repeated every 7-weeks provided the participant continued to benefit from and tolerate the therapy (Up to 115 Weeks), or Gemcitabine 1,000 mg/m^2 over 30 minutes, intravenously, on Days 1, 8, and 15 of a 28-day cycle until the absence of disease progression or unacceptable toxicity (Up to 32 Weeks), or Romidepsin 14 mg/m^2, intravenously over a 4-hour period, on Days 1, 8, and 15 of a 28-cycle. Cycles were repeated every 28 days provided the patient continued to benefit from and tolerate the therapy (Up to 30 Weeks).
Overall Number of Participants Analyzed 34 41
Median (95% Confidence Interval)
Unit of Measure: days
225 [1] 
(125 to NA)
172 [1] 
(119 to NA)
[1]
Upper Limit Confidence Interval was not estimable due to the insufficient number of participants with the event.
10.Secondary Outcome
Title Time to Response
Hide Description Time to Response is defined as the time from the date of randomization to the date of first documentation of PR or better.
Time Frame At the end of every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until progressive disease. Duration is approximately 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All responders in response-evaluable population defined as participants with peripheral T-cell lymphoma confirmed by independent hematopathology central review with measurable disease at baseline who receive at least 1 dose of alisertib or comparator drug and 1 postbaseline response assessment of CR, PR, SD or PD by independent radiology committee.
Arm/Group Title Alisertib Pralatrexate, or Romidepsin, or Gemcitabine
Hide Arm/Group Description:
Alisertib 50 mg, enteric-coated tablet formulation, orally, twice daily for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle (Up to 148 Weeks).
Pralatrexate 30 mg/m^2, intravenous (IV) push over 3 to 5 minutes, once weekly, for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles were repeated every 7-weeks provided the participant continued to benefit from and tolerate the therapy (Up to 115 Weeks), or Gemcitabine 1,000 mg/m^2 over 30 minutes, intravenously, on Days 1, 8, and 15 of a 28-day cycle until the absence of disease progression or unacceptable toxicity (Up to 32 Weeks), or Romidepsin 14 mg/m^2, intravenously over a 4-hour period, on Days 1, 8, and 15 of a 28-cycle. Cycles were repeated every 28 days provided the patient continued to benefit from and tolerate the therapy (Up to 30 Weeks).
Overall Number of Participants Analyzed 34 41
Median (95% Confidence Interval)
Unit of Measure: days
62
(57 to 67)
64
(60 to 71)
11.Secondary Outcome
Title Time to Subsequent Antineoplastic Therapy
Hide Description Time to subsequent antineoplastic therapy was defined as the time from randomization to the first date of subsequent antineoplastic therapy (excluding transplant). Participants without subsequent antineoplastic therapy were censored at the date of death or last known to be alive.
Time Frame From date of last study drug to date of subsequent antineoplastic therapy, if required; approximately 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population was defined as all participants who were randomized. The participants were analyzed according to the treatment they were randomized to receive, regardless of any errors of dosing.
Arm/Group Title Alisertib Pralatrexate, or Romidepsin, or Gemcitabine
Hide Arm/Group Description:
Alisertib 50 mg, enteric-coated tablet formulation, orally, twice daily for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle (Up to 148 Weeks).
Pralatrexate 30 mg/m^2, intravenous (IV) push over 3 to 5 minutes, once weekly, for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles were repeated every 7-weeks provided the participant continued to benefit from and tolerate the therapy (Up to 115 Weeks), or Gemcitabine 1,000 mg/m^2 over 30 minutes, intravenously, on Days 1, 8, and 15 of a 28-day cycle until the absence of disease progression or unacceptable toxicity (Up to 32 Weeks), or Romidepsin 14 mg/m^2, intravenously over a 4-hour period, on Days 1, 8, and 15 of a 28-cycle. Cycles were repeated every 28 days provided the patient continued to benefit from and tolerate the therapy (Up to 30 Weeks).
Overall Number of Participants Analyzed 138 133
Median (95% Confidence Interval)
Unit of Measure: days
336
(201 to 490)
233
(144 to 429)
12.Secondary Outcome
Title Plasma Concentration-time Data to Contribute to Future Population Pharmacokinetics (PK) Analysis
Hide Description [Not Specified]
Time Frame Cycle 1, Days 1 and 7; Cycle 2, Day 8; Cycle 3, Day 8; Cycle 4, Day 8. Duration is approximately 4 months.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This Outcome Measure was registered in error and is not a Primary or Secondary Outcome Measure.
Arm/Group Title Alisertib
Hide Arm/Group Description:
Alisertib 50 mg, enteric-coated tablet formulation, orally, twice daily for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle (Up to 148 Weeks).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
13.Secondary Outcome
Title Change Form Baseline in Reported Symptoms and Quality of Life (QoL) Assessment Per Functional Assessment of Cancer Therapy-Lymphoma (FACT-LYM) for Functioning and Symptoms
Hide Description The FACT-LYM includes the Functional Assessment of Cancer Therapy General Scale (FACT-G) and a 15-item lymphoma-specific subscale (LYM) over the past week. The FACT-G has 27 items that incorporate 4 scales including physical well-being (PWB; 7 items), social/family well-being (SWB, 7 items), emotional well-being (EWB; 6 items), and functional well-being (FWB; 7 items). The combined FACT-LYM instrument consists of a total of a 42 item questionnaire. Each question is answered on a 5- point scale of 0 (not at all) to 4 (very much) for a total possible score of 168. Higher scores indicate better well-being and a positive change from Baseline indicates improvement.
Time Frame Baseline and End of Treatment (EOT) (Up to 152 Weeks)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population was defined as all participants who were randomized. The participants were analyzed according to the treatment they were randomized to receive, regardless of any errors of dosing.
Arm/Group Title Alisertib Pralatrexate, or Romidepsin, or Gemcitabine
Hide Arm/Group Description:
Alisertib 50 mg, enteric-coated tablet formulation, orally, twice daily for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle (Up to 148 Weeks).
Pralatrexate 30 mg/m^2, intravenous (IV) push over 3 to 5 minutes, once weekly, for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles were repeated every 7-weeks provided the participant continued to benefit from and tolerate the therapy (Up to 115 Weeks), or Gemcitabine 1,000 mg/m^2 over 30 minutes, intravenously, on Days 1, 8, and 15 of a 28-day cycle until the absence of disease progression or unacceptable toxicity (Up to 32 Weeks), or Romidepsin 14 mg/m^2, intravenously over a 4-hour period, on Days 1, 8, and 15 of a 28-cycle. Cycles were repeated every 28 days provided the patient continued to benefit from and tolerate the therapy (Up to 30 Weeks).
Overall Number of Participants Analyzed 138 133
Mean (Standard Deviation)
Unit of Measure: score on a scale
Physical Well-Being, EOT Number Analyzed 81 participants 70 participants
-2.4  (6.21) -1.3  (5.27)
Social/Family Well-Being, EOT Number Analyzed 81 participants 69 participants
-0.3  (4.50) 0.0  (4.44)
Emotional Well-Being, EOT Number Analyzed 80 participants 67 participants
-1.4  (4.59) -0.8  (3.93)
Functional Well-Being, EOT Number Analyzed 80 participants 66 participants
-2.4  (5.40) -0.3  (4.79)
Time Frame First dose to 30 days after last dose of study drug or comparator (Up to 152 Weeks)
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Adverse events for arm "Gemcitabine or Pralatrexate or Romidepsin" were reported separately for each treatment received and reported as Gemcitabine, Pralatrexate, and Romidepsin.
 
Arm/Group Title Alisertib Gemcitabine Pralatrexate Romidepsin
Hide Arm/Group Description Alisertib 50 mg, enteric-coated tablet formulation, orally, twice daily for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle (Up to 148 Weeks). Gemcitabine 1,000 mg/m^2 over 30 minutes, intravenously, on Days 1, 8, and 15 of a 28-day cycle until the absence of disease progression or unacceptable toxicity (Up to 32 Weeks). Pralatrexate 30 mg/m^2, intravenous (IV) push over 3 to 5 minutes, once weekly, for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles were repeated every 7-weeks provided the participant continued to benefit from and tolerate the therapy (Up to 115 Weeks). Romidepsin 14 mg/m^2, intravenously over a 4-hour period, on Days 1, 8, and 15 of a 28-cycle. Cycles were repeated every 28 days provided the patient continued to benefit from and tolerate the therapy (Up to 30 Weeks).
All-Cause Mortality
Alisertib Gemcitabine Pralatrexate Romidepsin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/137 (8.03%)   5/29 (17.24%)   8/76 (10.53%)   2/22 (9.09%) 
Show Serious Adverse Events Hide Serious Adverse Events
Alisertib Gemcitabine Pralatrexate Romidepsin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   75/137 (54.74%)   18/29 (62.07%)   46/76 (60.53%)   6/22 (27.27%) 
Blood and lymphatic system disorders         
Febrile neutropenia  1  24/137 (17.52%)  1/29 (3.45%)  1/76 (1.32%)  0/22 (0.00%) 
Neutropenia  1  2/137 (1.46%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Thrombocytopenia  1  7/137 (5.11%)  1/29 (3.45%)  4/76 (5.26%)  0/22 (0.00%) 
Anaemia  1  7/137 (5.11%)  0/29 (0.00%)  2/76 (2.63%)  0/22 (0.00%) 
Microcytic anaemia  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Pancytopenia  1  3/137 (2.19%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Leukopenia  1  2/137 (1.46%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Cardiac disorders         
Cardiac failure  1  1/137 (0.73%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Cardiac failure congestive  1  0/137 (0.00%)  0/29 (0.00%)  0/76 (0.00%)  1/22 (4.55%) 
Cardiopulmonary failure  1 [1]  0/137 (0.00%)  1/29 (3.45%)  0/76 (0.00%)  0/22 (0.00%) 
Atrial fibrillation  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  2/22 (9.09%) 
Sinus tachycardia  1  0/137 (0.00%)  1/29 (3.45%)  0/76 (0.00%)  0/22 (0.00%) 
Bradycardia  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Tachycardia  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Atrioventricular block second degree  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Cardiomegaly  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Pericarditis  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Ear and labyrinth disorders         
Vertigo  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Gastrointestinal disorders         
Stomatitis  1  7/137 (5.11%)  0/29 (0.00%)  11/76 (14.47%)  0/22 (0.00%) 
Diarrhoea  1  6/137 (4.38%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Abdominal pain  1  1/137 (0.73%)  1/29 (3.45%)  2/76 (2.63%)  0/22 (0.00%) 
Nausea  1  2/137 (1.46%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Vomiting  1  3/137 (2.19%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Intestinal perforation  1 [1]  0/137 (0.00%)  1/29 (3.45%)  0/76 (0.00%)  0/22 (0.00%) 
Jejunal perforation  1  0/137 (0.00%)  1/29 (3.45%)  0/76 (0.00%)  0/22 (0.00%) 
Pancreatitis  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Dysphagia  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Ileus  1 [2]  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Haematemesis  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Mouth haemorrhage  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Ascites  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
General disorders         
Pyrexia  1  12/137 (8.76%)  6/29 (20.69%)  6/76 (7.89%)  1/22 (4.55%) 
General physical health deterioration  1 [3]  1/137 (0.73%)  0/29 (0.00%)  3/76 (3.95%)  0/22 (0.00%) 
Multiple organ dysfunction syndrome  1 [4]  1/137 (0.73%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Influenza like illness  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Fatigue  1  1/137 (0.73%)  0/29 (0.00%)  1/76 (1.32%)  1/22 (4.55%) 
Hypothermia  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Catheter site phlebitis  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Oedema peripheral  1  0/137 (0.00%)  0/29 (0.00%)  0/76 (0.00%)  1/22 (4.55%) 
Pain  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Adverse drug reaction  1 [5]  0/137 (0.00%)  1/29 (3.45%)  0/76 (0.00%)  0/22 (0.00%) 
Hepatobiliary disorders         
Drug-induced liver injury  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Hepatotoxicity  1  0/137 (0.00%)  1/29 (3.45%)  0/76 (0.00%)  0/22 (0.00%) 
Cholangitis acute  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Cholestasis  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Hepatic failure  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Venoocclusive liver disease  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Immune system disorders         
Hypersensitivity  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Anaphylactoid reaction  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Infections and infestations         
Pneumonia  1 [6]  9/137 (6.57%)  0/29 (0.00%)  4/76 (5.26%)  0/22 (0.00%) 
Lung infection  1  1/137 (0.73%)  1/29 (3.45%)  2/76 (2.63%)  0/22 (0.00%) 
Lower respiratory tract infection  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Sepsis  1 [7]  2/137 (1.46%)  0/29 (0.00%)  2/76 (2.63%)  0/22 (0.00%) 
Septic shock  1 [8]  4/137 (2.92%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Skin infection  1 [2]  1/137 (0.73%)  0/29 (0.00%)  2/76 (2.63%)  0/22 (0.00%) 
Dermatitis infected  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Upper respiratory tract infection  1  1/137 (0.73%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Epiglottitis  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Tonsillitis  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Cytomegalovirus infection  1  1/137 (0.73%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Cytomegalovirus chorioretinitis  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Cellulitis  1  0/137 (0.00%)  1/29 (3.45%)  0/76 (0.00%)  0/22 (0.00%) 
Pneumonia bacterial  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Clostridium difficile colitis  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Clostridium difficile infection  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Respiratory tract infection  1  2/137 (1.46%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Wound infection  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Pseudomonal sepsis  1  0/137 (0.00%)  0/29 (0.00%)  2/76 (2.63%)  0/22 (0.00%) 
Erysipelas  1  2/137 (1.46%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Gastroenteritis  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Meningitis aseptic  1  0/137 (0.00%)  1/29 (3.45%)  0/76 (0.00%)  0/22 (0.00%) 
Oral infection  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Pneumonia haemophilus  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Eczema herpeticum  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Staphylococcal sepsis  1  0/137 (0.00%)  0/29 (0.00%)  0/76 (0.00%)  1/22 (4.55%) 
Urinary tract infection  1  2/137 (1.46%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Staphylococcal skin infection  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Injury, poisoning and procedural complications         
Fall  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Contusion  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Spinal compression fracture  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Investigations         
Lymphocyte count decreased  1  0/137 (0.00%)  0/29 (0.00%)  0/76 (0.00%)  1/22 (4.55%) 
White blood cell count decreased  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Blood lactate dehydrogenase increased  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Metabolism and nutrition disorders         
Dehydration  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  2/22 (9.09%) 
Decreased appetite  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Hypophagia  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Electrolyte imbalance  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Tumour lysis syndrome  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Hyperglycaemia  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Hypokalaemia  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Hypoalbuminaemia  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  1/137 (0.73%)  1/29 (3.45%)  2/76 (2.63%)  0/22 (0.00%) 
Pain in extremity  1  0/137 (0.00%)  1/29 (3.45%)  0/76 (0.00%)  0/22 (0.00%) 
Compartment syndrome  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Peripheral T-cell lymphoma unspecified  1 [9]  2/137 (1.46%)  2/29 (6.90%)  1/76 (1.32%)  2/22 (9.09%) 
Lymphoma  1 [7]  2/137 (1.46%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Anaplastic large cell lymphoma T- and null-cell types  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Adenocarcinoma of colon  1  0/137 (0.00%)  1/29 (3.45%)  0/76 (0.00%)  0/22 (0.00%) 
Squamous cell carcinoma  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Plasma cell myeloma  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Myelodysplastic syndrome  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Adult T-cell lymphoma/leukaemia  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Nervous system disorders         
Cerebrovascular accident  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Haemorrhage intracranial  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Syncope  1  2/137 (1.46%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Carotid artery aneurysm  1  0/137 (0.00%)  1/29 (3.45%)  0/76 (0.00%)  0/22 (0.00%) 
Hepatic encephalopathy  1  0/137 (0.00%)  1/29 (3.45%)  0/76 (0.00%)  0/22 (0.00%) 
Facial paralysis  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Presyncope  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Renal and urinary disorders         
Acute kidney injury  1  2/137 (1.46%)  0/29 (0.00%)  2/76 (2.63%)  0/22 (0.00%) 
Acute prerenal failure  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Renal failure  1  0/137 (0.00%)  1/29 (3.45%)  0/76 (0.00%)  0/22 (0.00%) 
Cystitis haemorrhagic  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Hydronephrosis  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Dyspnoea  1  2/137 (1.46%)  2/29 (6.90%)  3/76 (3.95%)  2/22 (9.09%) 
Respiratory distress  1  0/137 (0.00%)  0/29 (0.00%)  0/76 (0.00%)  1/22 (4.55%) 
Sleep apnoea syndrome  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Hypoxia  1 [10]  2/137 (1.46%)  0/29 (0.00%)  2/76 (2.63%)  0/22 (0.00%) 
Pulmonary embolism  1  1/137 (0.73%)  1/29 (3.45%)  1/76 (1.32%)  0/22 (0.00%) 
Respiratory failure  1 [1]  0/137 (0.00%)  1/29 (3.45%)  2/76 (2.63%)  0/22 (0.00%) 
Pleural effusion  1 [2]  1/137 (0.73%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Chronic obstructive pulmonary disease  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Cough  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Hiccups  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Interstitial lung disease  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Skin and subcutaneous tissue disorders         
Rash maculo-papular  1  2/137 (1.46%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Rash  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Dermatitis bullous  1  0/137 (0.00%)  0/29 (0.00%)  2/76 (2.63%)  0/22 (0.00%) 
Toxic epidermal necrolysis  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Pain of skin  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Acute generalised exanthematous pustulosis  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Vascular disorders         
Shock haemorrhagic  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Thrombosis  1  0/137 (0.00%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Deep vein thrombosis  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
Orthostatic hypotension  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  0/22 (0.00%) 
1
Term from vocabulary, MedDRA version 15.0
Indicates events were collected by systematic assessment
[1]
One treatment-emergent death occurred during treatment with gemcitabine and is not related.
[2]
One treatment-emergent death occurred during treatment with pralatrexate and is not related.
[3]
Three treatment-emergent deaths occurred during treatment with pralatrexate and are not related.
[4]
Two treatment-emergent deaths occurred during treatment, one with alisertib, not related and one with pralatrexate, related.
[5]
One treatment-emergent death occurred during treatment with gemcitabine and is related.
[6]
One treatment-emergent death occurred during treatment with alisertib and is related.
[7]
One treatment-emergent death occurred during treatment with alisertib and is not related.
[8]
Four treatment-emergent deaths occurred during treatment with alisertib, two related and two not related.
[9]
Five treatment-emergent deaths occurred during treatment and are not related, two with alisertib, one with gemcitabine, and two with romidepsin.
[10]
Two treatment-emergent deaths occurred during treatment, one with alisertib and one with pralatrexate and are not related.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Alisertib Gemcitabine Pralatrexate Romidepsin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   134/137 (97.81%)   29/29 (100.00%)   72/76 (94.74%)   21/22 (95.45%) 
Blood and lymphatic system disorders         
Anaemia  1  74/137 (54.01%)  7/29 (24.14%)  30/76 (39.47%)  6/22 (27.27%) 
Neutropenia  1  66/137 (48.18%)  11/29 (37.93%)  21/76 (27.63%)  7/22 (31.82%) 
Thrombocytopenia  1  51/137 (37.23%)  12/29 (41.38%)  29/76 (38.16%)  7/22 (31.82%) 
Leukopenia  1  39/137 (28.47%)  6/29 (20.69%)  6/76 (7.89%)  2/22 (9.09%) 
Lymphopenia  1  14/137 (10.22%)  2/29 (6.90%)  5/76 (6.58%)  1/22 (4.55%) 
Febrile neutropenia  1  7/137 (5.11%)  1/29 (3.45%)  1/76 (1.32%)  0/22 (0.00%) 
Lymph node pain  1  1/137 (0.73%)  2/29 (6.90%)  1/76 (1.32%)  0/22 (0.00%) 
Cardiac disorders         
Tachycardia  1  5/137 (3.65%)  0/29 (0.00%)  4/76 (5.26%)  0/22 (0.00%) 
Angina pectoris  1  0/137 (0.00%)  0/29 (0.00%)  0/76 (0.00%)  2/22 (9.09%) 
Palpitations  1  0/137 (0.00%)  2/29 (6.90%)  0/76 (0.00%)  0/22 (0.00%) 
Gastrointestinal disorders         
Diarrhoea  1  61/137 (44.53%)  5/29 (17.24%)  18/76 (23.68%)  10/22 (45.45%) 
Stomatitis  1  42/137 (30.66%)  0/29 (0.00%)  48/76 (63.16%)  2/22 (9.09%) 
Nausea  1  35/137 (25.55%)  7/29 (24.14%)  23/76 (30.26%)  15/22 (68.18%) 
Constipation  1  17/137 (12.41%)  6/29 (20.69%)  20/76 (26.32%)  3/22 (13.64%) 
Vomiting  1  18/137 (13.14%)  3/29 (10.34%)  15/76 (19.74%)  4/22 (18.18%) 
Abdominal pain  1  16/137 (11.68%)  1/29 (3.45%)  7/76 (9.21%)  2/22 (9.09%) 
Dyspepsia  1  12/137 (8.76%)  1/29 (3.45%)  5/76 (6.58%)  2/22 (9.09%) 
Abdominal pain upper  1  8/137 (5.84%)  2/29 (6.90%)  2/76 (2.63%)  0/22 (0.00%) 
Mouth ulceration  1  5/137 (3.65%)  0/29 (0.00%)  5/76 (6.58%)  0/22 (0.00%) 
Odynophagia  1  2/137 (1.46%)  0/29 (0.00%)  5/76 (6.58%)  0/22 (0.00%) 
General disorders         
Fatigue  1  49/137 (35.77%)  11/29 (37.93%)  14/76 (18.42%)  6/22 (27.27%) 
Pyrexia  1  42/137 (30.66%)  7/29 (24.14%)  20/76 (26.32%)  3/22 (13.64%) 
Oedema peripheral  1  21/137 (15.33%)  5/29 (17.24%)  10/76 (13.16%)  5/22 (22.73%) 
Asthenia  1  24/137 (17.52%)  2/29 (6.90%)  10/76 (13.16%)  0/22 (0.00%) 
Chills  1  9/137 (6.57%)  2/29 (6.90%)  5/76 (6.58%)  2/22 (9.09%) 
Malaise  1  4/137 (2.92%)  3/29 (10.34%)  1/76 (1.32%)  1/22 (4.55%) 
Mucosal inflammation  1  3/137 (2.19%)  1/29 (3.45%)  5/76 (6.58%)  0/22 (0.00%) 
Peripheral swelling  1  1/137 (0.73%)  2/29 (6.90%)  2/76 (2.63%)  0/22 (0.00%) 
Chest discomfort  1  1/137 (0.73%)  0/29 (0.00%)  0/76 (0.00%)  2/22 (9.09%) 
Infections and infestations         
Upper respiratory tract infection  1  14/137 (10.22%)  3/29 (10.34%)  3/76 (3.95%)  1/22 (4.55%) 
Influenza  1  8/137 (5.84%)  1/29 (3.45%)  3/76 (3.95%)  0/22 (0.00%) 
Conjunctivitis  1  4/137 (2.92%)  0/29 (0.00%)  7/76 (9.21%)  0/22 (0.00%) 
Pneumonia  1  4/137 (2.92%)  0/29 (0.00%)  5/76 (6.58%)  1/22 (4.55%) 
Sinusitis  1  5/137 (3.65%)  0/29 (0.00%)  2/76 (2.63%)  3/22 (13.64%) 
Viral upper respiratory tract infection  1  4/137 (2.92%)  2/29 (6.90%)  3/76 (3.95%)  1/22 (4.55%) 
Skin infection  1  2/137 (1.46%)  1/29 (3.45%)  6/76 (7.89%)  0/22 (0.00%) 
Bronchitis  1  4/137 (2.92%)  0/29 (0.00%)  4/76 (5.26%)  0/22 (0.00%) 
Pharyngitis  1  3/137 (2.19%)  0/29 (0.00%)  4/76 (5.26%)  0/22 (0.00%) 
Oral herpes  1  3/137 (2.19%)  3/29 (10.34%)  0/76 (0.00%)  0/22 (0.00%) 
Mucosal infection  1  0/137 (0.00%)  0/29 (0.00%)  4/76 (5.26%)  0/22 (0.00%) 
Investigations         
Platelet count decreased  1  16/137 (11.68%)  11/29 (37.93%)  6/76 (7.89%)  5/22 (22.73%) 
Neutrophil count decreased  1  18/137 (13.14%)  5/29 (17.24%)  5/76 (6.58%)  4/22 (18.18%) 
White blood cell count decreased  1  16/137 (11.68%)  5/29 (17.24%)  3/76 (3.95%)  2/22 (9.09%) 
Alanine aminotransferase increased  1  8/137 (5.84%)  2/29 (6.90%)  9/76 (11.84%)  0/22 (0.00%) 
Weight decreased  1  12/137 (8.76%)  1/29 (3.45%)  6/76 (7.89%)  0/22 (0.00%) 
Aspartate aminotransferase increased  1  5/137 (3.65%)  3/29 (10.34%)  8/76 (10.53%)  0/22 (0.00%) 
Blood alkaline phosphatase increased  1  9/137 (6.57%)  1/29 (3.45%)  5/76 (6.58%)  1/22 (4.55%) 
Blood creatinine increased  1  3/137 (2.19%)  3/29 (10.34%)  3/76 (3.95%)  2/22 (9.09%) 
Haemoglobin decreased  1  1/137 (0.73%)  2/29 (6.90%)  1/76 (1.32%)  0/22 (0.00%) 
Metabolism and nutrition disorders         
Decreased appetite  1  27/137 (19.71%)  1/29 (3.45%)  14/76 (18.42%)  9/22 (40.91%) 
Hypokalaemia  1  13/137 (9.49%)  0/29 (0.00%)  5/76 (6.58%)  2/22 (9.09%) 
Hypomagnesaemia  1  9/137 (6.57%)  1/29 (3.45%)  6/76 (7.89%)  0/22 (0.00%) 
Dehydration  1  4/137 (2.92%)  0/29 (0.00%)  7/76 (9.21%)  2/22 (9.09%) 
Hyponatraemia  1  3/137 (2.19%)  0/29 (0.00%)  4/76 (5.26%)  1/22 (4.55%) 
Musculoskeletal and connective tissue disorders         
Pain in extremity  1  15/137 (10.95%)  3/29 (10.34%)  6/76 (7.89%)  1/22 (4.55%) 
Back pain  1  12/137 (8.76%)  0/29 (0.00%)  6/76 (7.89%)  0/22 (0.00%) 
Arthralgia  1  8/137 (5.84%)  1/29 (3.45%)  3/76 (3.95%)  1/22 (4.55%) 
Muscle spasms  1  9/137 (6.57%)  2/29 (6.90%)  1/76 (1.32%)  1/22 (4.55%) 
Musculoskeletal pain  1  7/137 (5.11%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Nervous system disorders         
Dizziness  1  16/137 (11.68%)  2/29 (6.90%)  6/76 (7.89%)  1/22 (4.55%) 
Headache  1  15/137 (10.95%)  2/29 (6.90%)  5/76 (6.58%)  2/22 (9.09%) 
Somnolence  1  15/137 (10.95%)  0/29 (0.00%)  1/76 (1.32%)  1/22 (4.55%) 
Dysgeusia  1  3/137 (2.19%)  0/29 (0.00%)  2/76 (2.63%)  4/22 (18.18%) 
Disturbance in attention  1  2/137 (1.46%)  0/29 (0.00%)  0/76 (0.00%)  2/22 (9.09%) 
Psychiatric disorders         
Insomnia  1  12/137 (8.76%)  2/29 (6.90%)  3/76 (3.95%)  1/22 (4.55%) 
Anxiety  1  5/137 (3.65%)  1/29 (3.45%)  4/76 (5.26%)  3/22 (13.64%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  14/137 (10.22%)  4/29 (13.79%)  17/76 (22.37%)  3/22 (13.64%) 
Dyspnoea  1  12/137 (8.76%)  4/29 (13.79%)  8/76 (10.53%)  4/22 (18.18%) 
Epistaxis  1  5/137 (3.65%)  1/29 (3.45%)  11/76 (14.47%)  1/22 (4.55%) 
Oropharyngeal pain  1  6/137 (4.38%)  1/29 (3.45%)  6/76 (7.89%)  1/22 (4.55%) 
Productive cough  1  4/137 (2.92%)  1/29 (3.45%)  4/76 (5.26%)  0/22 (0.00%) 
Nasal congestion  1  1/137 (0.73%)  1/29 (3.45%)  4/76 (5.26%)  2/22 (9.09%) 
Hypoxia  1  2/137 (1.46%)  2/29 (6.90%)  1/76 (1.32%)  2/22 (9.09%) 
Skin and subcutaneous tissue disorders         
Alopecia  1  43/137 (31.39%)  0/29 (0.00%)  1/76 (1.32%)  0/22 (0.00%) 
Pruritus  1  19/137 (13.87%)  1/29 (3.45%)  11/76 (14.47%)  5/22 (22.73%) 
Rash  1  5/137 (3.65%)  1/29 (3.45%)  7/76 (9.21%)  1/22 (4.55%) 
Night sweats  1  5/137 (3.65%)  2/29 (6.90%)  4/76 (5.26%)  1/22 (4.55%) 
Skin lesion  1  2/137 (1.46%)  2/29 (6.90%)  4/76 (5.26%)  1/22 (4.55%) 
Skin ulcer  1  3/137 (2.19%)  0/29 (0.00%)  4/76 (5.26%)  0/22 (0.00%) 
Vascular disorders         
Hypertension  1  5/137 (3.65%)  2/29 (6.90%)  2/76 (2.63%)  3/22 (13.64%) 
Hypotension  1  4/137 (2.92%)  2/29 (6.90%)  2/76 (2.63%)  2/22 (9.09%) 
1
Term from vocabulary, MedDRA version 15.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Results Point of Contact
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT01482962     History of Changes
Other Study ID Numbers: C14012
2011-003545-18 ( EudraCT Number )
DRKS00004503 ( Registry Identifier: Germany (DRKS) )
NL39566.068.12 ( Registry Identifier: Netherlands (CCMO) )
U1111-1181-8218 ( Registry Identifier: WHO )
First Submitted: November 28, 2011
First Posted: December 1, 2011
Results First Submitted: May 9, 2018
Results First Posted: July 31, 2018
Last Update Posted: July 31, 2018