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MLN8237 in Patients With Relapsed or Refractory Aggressive B-Cell Lymphoma Treated With Rituximab +/- Vincristine

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ClinicalTrials.gov Identifier: NCT01397825
Recruitment Status : Completed
First Posted : July 20, 2011
Results First Posted : March 27, 2018
Last Update Posted : March 27, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Diffuse Large B-Cell Lymphoma
Transformed Follicular Lymphoma
Mantle Cell Lymphoma
Burkitt's Lymphoma
Interventions Drug: Alisertib (MLN8237)
Drug: Rituximab
Drug: Vincristine
Enrollment 45
Recruitment Details Participants took part in the Phase 1 portion of the study at 10 investigative sites in the United States from 09 August 2011 to 05 October 2016. The Phase 2 portion of the study was cancelled by the sponsor.
Pre-assignment Details Participants with a diagnosis of relapsed or refractory Diffuse Large B-cell lymphoma (DLBCL)/transformed Follicular lymphoma (TFL), Mantle Cell lymphoma, or Burkitt’s Lymphoma were enrolled to receive alisertib open label at doses 30 mg, 40 mg or 50 mg.
Arm/Group Title Safety Lead-in Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg Phase 2: Alisertib
Hide Arm/Group Description Alisertib 50 mg, enteric coated tablets (ECT), orally, twice daily (BID), on Days 1 to 7 followed by a 14-day rest period in 21-day cycles plus rituximab 375 mg/m^2, intravenous (IV), infusion on Day 1 of each 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years. Alisertib 30 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1, plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years. Alisertib 40 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years. Alisertib 50 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years. Phase 2: Alisertib (MLN8237) at the Recommended Phase 2 Dose, ECT orally twice/day on Days 1-7 & rituximab as an IV infusion on Day 1 & vincristine IV on Days 1 & 8 in a 21 Day cycle for up to 8 cycles was planned but not conducted.
Period Title: Overall Study
Started 13 4 25 3 0
Completed 0 0 0 0 0
Not Completed 13 4 25 3 0
Reason Not Completed
Progressive Disease             10             3             11             1             0
Symptomatic Deterioration             2             0             4             0             0
Adverse Event             0             1             5             1             0
Withdrawal by Subject             1             0             5             1             0
Arm/Group Title Safety Lead-in Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg Total
Hide Arm/Group Description Alisertib 50 mg, enteric coated tablets (ECT), orally, twice daily (BID), on Days 1 to 7 followed by a 14-day rest period in 21-day cycles plus rituximab 375 mg/m^2, intravenous (IV), infusion on Day 1 of each 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years. Alisertib 30 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1, plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years. Alisertib 40 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years. Alisertib 50 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years. Total of all reporting groups
Overall Number of Baseline Participants 13 4 25 3 45
Hide Baseline Analysis Population Description
Safety Population was defined as all participants who receive any amount of alisertib.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 13 participants 4 participants 25 participants 3 participants 45 participants
60.3  (14.06) 51.3  (21.65) 62.8  (10.51) 66.7  (12.86) 61.3  (12.89)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 4 participants 25 participants 3 participants 45 participants
Female
3
  23.1%
1
  25.0%
10
  40.0%
2
  66.7%
16
  35.6%
Male
10
  76.9%
3
  75.0%
15
  60.0%
1
  33.3%
29
  64.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13 participants 4 participants 25 participants 3 participants 45 participants
Hispanic or Latino 7 1 6 1 15
Not Hispanic or Latino 6 3 19 2 30
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 13 participants 4 participants 25 participants 3 participants 45 participants
White 12 4 21 3 40
Black or African American 0 0 2 0 2
Asian 1 0 0 0 1
Other 0 0 1 0 1
Not Reported 0 0 1 0 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 13 participants 4 participants 25 participants 3 participants 45 participants
13 4 25 3 45
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 13 participants 4 participants 25 participants 3 participants 45 participants
167.9  (10.90) 178.2  (7.15) 168.4  (10.76) 166.5  (5.32) 169.0  (10.44)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 13 participants 4 participants 25 participants 3 participants 45 participants
70.98  (16.18) 89.51  (23.89) 82.21  (16.4) 71.94  (14.55) 78.93  (17.46)
Body Surface Area   [1] 
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 13 participants 4 participants 25 participants 3 participants 45 participants
1.815  (0.25) 2.093  (0.31) 1.940  (0.23) 1.823  (0.21) 1.910  (0.25)
[1]
Measure Description: Body surface area (m^²)=square root [height (cm)×weight (kg)/3600].
1.Primary Outcome
Title Number of Participants With Clinically Significant Vital Signs Findings (Treatment Related and Unrelated) [Phase 1]
Hide Description Vital sign parameters: blood pressure, heart rate and temperature determined by the investigator to be clinically significant were reported as adverse events.
Time Frame First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population was defined as all participants who receive any amount of alisertib.
Arm/Group Title Safety Lead-in Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg
Hide Arm/Group Description:
Alisertib 50 mg, enteric coated tablets (ECT), orally, twice daily (BID), on Days 1 to 7 followed by a 14-day rest period in 21-day cycles plus rituximab 375 mg/m^2, intravenous (IV), infusion on Day 1 of each 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 30 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1, plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 40 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 50 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Overall Number of Participants Analyzed 13 4 25 3
Measure Type: Number
Unit of Measure: participants
Hypotension 0 0 3 1
Orthostatic hypotension 2 2 0 0
Hypertension 1 0 0 0
Pyrexia 3 0 2 1
2.Primary Outcome
Title Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs) [Phase 1]
Hide Description Abnormal ECGs findings determined by the investigator to be clinically significant were reported as adverse events.
Time Frame First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population was defined as all participants who receive any amount of alisertib.
Arm/Group Title Safety Lead-in Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg
Hide Arm/Group Description:
Alisertib 50 mg, enteric coated tablets (ECT), orally, twice daily (BID), on Days 1 to 7 followed by a 14-day rest period in 21-day cycles plus rituximab 375 mg/m^2, intravenous (IV), infusion on Day 1 of each 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 30 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1, plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 40 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 50 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Overall Number of Participants Analyzed 13 4 25 3
Measure Type: Number
Unit of Measure: participants
0 0 0 0
3.Primary Outcome
Title Number of Participants With Clinically Significant Changes in Multigated Acquisition (MUGA)/ Echocardiogram (ECHO) [Phase 1]
Hide Description Abnormal changes in MUGA and ECHO findings determined by the investigator to be clinically significant were reported as adverse events.
Time Frame First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population was defined as all participants who receive any amount of alisertib.
Arm/Group Title Safety Lead-in Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg
Hide Arm/Group Description:
Alisertib 50 mg, enteric coated tablets (ECT), orally, twice daily (BID), on Days 1 to 7 followed by a 14-day rest period in 21-day cycles plus rituximab 375 mg/m^2, intravenous (IV), infusion on Day 1 of each 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 30 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1, plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 40 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 50 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Overall Number of Participants Analyzed 13 4 25 3
Measure Type: Number
Unit of Measure: participants
0 0 0 0
4.Primary Outcome
Title Number of Participants With Clinically Significant Changes in Physical Examination Findings [Phase 1]
Hide Description Abnormal Physical Examination findings determined by the investigator to be clinically significant were reported as Adverse Events.
Time Frame First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population was defined as all participants who receive any amount of alisertib.
Arm/Group Title Safety Lead-in Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg
Hide Arm/Group Description:
Alisertib 50 mg, enteric coated tablets (ECT), orally, twice daily (BID), on Days 1 to 7 followed by a 14-day rest period in 21-day cycles plus rituximab 375 mg/m^2, intravenous (IV), infusion on Day 1 of each 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 30 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1, plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 40 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 50 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Overall Number of Participants Analyzed 13 4 25 3
Measure Type: Number
Unit of Measure: participants
0 0 2 2
5.Primary Outcome
Title Number of Participants With Clinically Significant Laboratory Tests Reported as Adverse Events [Phase 1]
Hide Description Abnormal treatment-emergent Chemistry and Hematology Laboratory values determined by the investigator to be clinically significant were reported as adverse events.
Time Frame First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population was defined as all participants who receive any amount of alisertib.
Arm/Group Title Safety Lead-in Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg
Hide Arm/Group Description:
Alisertib 50 mg, enteric coated tablets (ECT), orally, twice daily (BID), on Days 1 to 7 followed by a 14-day rest period in 21-day cycles plus rituximab 375 mg/m^2, intravenous (IV), infusion on Day 1 of each 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 30 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1, plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 40 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 50 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Overall Number of Participants Analyzed 13 4 25 3
Measure Type: Number
Unit of Measure: participants
Anaemia 6 3 14 2
Neutropenia 7 2 11 2
Febrile neutropenia 0 0 4 3
Leukopenia 8 2 9 3
Lymphopenia 2 2 1 1
Thrombocytopenia 7 1 7 3
Hypokalaemia 5 0 6 2
Hyperkalaemia 0 0 1 0
Hypomagnesaemia 2 0 5 1
Hypermagnesaemia 0 0 0 1
Hypocalcaemia 2 0 1 1
Hypercalcaemia 1 0 2 0
Hyperglycaemia 1 1 2 1
Hypoalbuminaemia 3 0 0 2
Hyponatraemia 2 0 0 1
Hypernatraemia 0 0 1 0
Hypophosphataemia 1 0 1 1
Neutrophil count decreased 1 0 3 1
Lymphocyte count decreased 1 0 0 0
White blood cell count decreased 0 0 0 1
Aspartate aminotransferase increased 0 0 1 2
Alanine aminotransferase increased 0 0 0 2
Blood bilirubin increased 1 0 0 0
Platelet count decreased 1 0 1 1
6.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events [Phase 1]
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 treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time Frame First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population was defined as all participants who receive any amount of alisertib.
Arm/Group Title Safety Lead-in Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg
Hide Arm/Group Description:
Alisertib 50 mg, enteric coated tablets (ECT), orally, twice daily (BID), on Days 1 to 7 followed by a 14-day rest period in 21-day cycles plus rituximab 375 mg/m^2, intravenous (IV), infusion on Day 1 of each 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 30 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1, plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 40 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 50 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Overall Number of Participants Analyzed 13 4 25 3
Measure Type: Number
Unit of Measure: participants
13 4 25 3
7.Primary Outcome
Title Overall Response Rate [Phase 2]
Hide Description Overall Response Rate was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) as assessed by the investigator using International Working Group (IWG) Criteria. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.
Time Frame At the end of Cycle 2, at the end of every second treatment cycle until 6 months, then every 12 weeks thereafter, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The Phase 2 portion of the study was cancelled by the sponsor.
Arm/Group Title Phase 2: Alisertib
Hide Arm/Group Description:
Phase 2: Alisertib (MLN8237) at the Recommended Phase 2 Dose, ECT orally twice/day on Days 1-7 & rituximab as an IV infusion on Day 1 & vincristine IV on Days 1 & 8 in a 21 Day cycle for up to 8 cycles was planned but not conducted.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Overall Response Rate as Assessed by the Investigator [Phase 1]
Hide Description Overall Response Rate was defined as the percentage of participants with Complete Response (CR) or Partial Response (PR) as assessed by the investigator using International Working Group (IWG) Criteria. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites.
Time Frame First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
Hide Outcome Measure Data
Hide Analysis Population Description
Response-Evaluable Population was defined as all participants with measurable disease who received at least 1 dose of alisertib and had at least 1 post-baseline response assessment.
Arm/Group Title Safety Lead-in Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg
Hide Arm/Group Description:
Alisertib 50 mg, enteric coated tablets (ECT), orally, twice daily (BID), on Days 1 to 7 followed by a 14-day rest period in 21-day cycles plus rituximab 375 mg/m^2, intravenous (IV), infusion on Day 1 of each 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 30 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1, plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 40 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 50 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Overall Number of Participants Analyzed 12 3 20 2
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
25
(5 to 57)
33
(0.84 to 91)
45
(23 to 68)
50
(1 to 99)
9.Secondary Outcome
Title Complete Response Rate [Phase 2]
Hide Description Complete response rate was defined as the percentage of participants with Complete Response (CR). CR was assessed by the investigator using International Working Group (IWG) Criteria. CR is defined as the disappearance of all evidence of disease.
Time Frame Duration of study until disease progression, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2 portion of the study was cancelled by the sponsor.
Arm/Group Title Phase 2: Alisertib
Hide Arm/Group Description:
Phase 2: Alisertib (MLN8237) at the Recommended Phase 2 Dose, ECT orally twice/day on Days 1-7 & rituximab as an IV infusion on Day 1 & vincristine IV on Days 1 & 8 in a 21 Day cycle for up to 8 cycles was planned but not conducted.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Duration of Response (DOR) [Phase 2]
Hide Description DOR was defined as the time from the date of first documentation of a response to the date of first documentation of Progressive Disease (PD).
Time Frame Duration of study until disease progression, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2 portion of the study was cancelled by the sponsor.
Arm/Group Title Phase 2: Alisertib
Hide Arm/Group Description:
Phase 2: Alisertib (MLN8237) at the Recommended Phase 2 Dose, ECT orally twice/day on Days 1-7 & rituximab as an IV infusion on Day 1 & vincristine IV on Days 1 & 8 in a 21 Day cycle for up to 8 cycles was planned but not conducted.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
11.Secondary Outcome
Title Progression Free Survival (PFS) [Phase 2]
Hide Description PFS was defined as the time from the date of first study drug administration to the date of first documentation of PD or death.
Time Frame Duration of study until disease progression, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The Phase 2 portion of the study was cancelled by the sponsor.
Arm/Group Title Phase 2: Alisertib
Hide Arm/Group Description:
Phase 2: Alisertib (MLN8237) at the Recommended Phase 2 Dose, ECT orally twice/day on Days 1-7 & rituximab as an IV infusion on Day 1 & vincristine IV on Days 1 & 8 in a 21 Day cycle for up to 8 cycles was planned but not conducted.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events [Phase 2]
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 treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time Frame From screening period to 30 days after last dose of study drug, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2 portion of the study was cancelled by the sponsor.
Arm/Group Title Phase 2: Alisertib
Hide Arm/Group Description:
Phase 2: Alisertib (MLN8237) at the Recommended Phase 2 Dose, ECT orally twice/day on Days 1-7 & rituximab as an IV infusion on Day 1 & vincristine IV on Days 1 & 8 in a 21 Day cycle for up to 8 cycles was planned but not conducted.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
13.Secondary Outcome
Title Number of Participants With Clinically Significant Vital Signs Findings [Phase 2]
Hide Description Vital sign parameters: blood pressure, heart rate and temperature determined by the investigator to be clinically significant were reported as adverse events.
Time Frame From screening period to 30 days after last dose of study drug, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2 portion of the study was cancelled by the sponsor.
Arm/Group Title Phase 2: Alisertib
Hide Arm/Group Description:
Phase 2: Alisertib (MLN8237) at the Recommended Phase 2 Dose, ECT orally twice/day on Days 1-7 & rituximab as an IV infusion on Day 1 & vincristine IV on Days 1 & 8 in a 21 Day cycle for up to 8 cycles was planned but not conducted.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
14.Secondary Outcome
Title Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs) [Phase 2]
Hide Description [Not Specified]
Time Frame From screening period to 30 days after last dose of study drug, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2 portion of the study was cancelled by the sponsor.
Arm/Group Title Phase 2: Alisertib
Hide Arm/Group Description:
Phase 2: Alisertib (MLN8237) at the Recommended Phase 2 Dose, ECT orally twice/day on Days 1-7 & rituximab as an IV infusion on Day 1 & vincristine IV on Days 1 & 8 in a 21 Day cycle for up to 8 cycles was planned but not conducted.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
15.Secondary Outcome
Title Number of Participants With Clinically Significant Changes in Multigated Acquisition (MUGA)/ Echocardiogram (ECHO) [Phase 2]
Hide Description [Not Specified]
Time Frame From screening period to 30 days after last dose of study drug, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2 portion of the study was cancelled by the sponsor.
Arm/Group Title Phase 2: Alisertib
Hide Arm/Group Description:
Phase 2: Alisertib (MLN8237) at the Recommended Phase 2 Dose, ECT orally twice/day on Days 1-7 & rituximab as an IV infusion on Day 1 & vincristine IV on Days 1 & 8 in a 21 Day cycle for up to 8 cycles was planned but not conducted.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
16.Secondary Outcome
Title Number of Participants With Clinically Significant Laboratory Tests Reported as Adverse Events [Phase 2]
Hide Description [Not Specified]
Time Frame From screening period to 30 days after last dose of study drug, approximately 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2 portion of the study was cancelled by the sponsor.
Arm/Group Title Phase 2: Alisertib
Hide Arm/Group Description:
Phase 2: Alisertib (MLN8237) at the Recommended Phase 2 Dose, ECT orally twice/day on Days 1-7 & rituximab as an IV infusion on Day 1 & vincristine IV on Days 1 & 8 in a 21 Day cycle for up to 8 cycles was planned but not conducted.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
17.Secondary Outcome
Title Cmax: Maximum Plasma Concentration for Alisertib
Hide Description [Not Specified]
Time Frame Cycle 1 Days 1 and 7 prior to morning alisertib dose and multiple time-points (up to 12 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Alisertib Pharmacokinetic (PK)-Evaluable Population was defined as all participants with sufficient dosing and alisertib concentration-time data to permit non-compartmental PK analysis. Number analyzed is the number of participants with data available at the given time-point.
Arm/Group Title Safety Lead-in Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg
Hide Arm/Group Description:
Alisertib 50 mg, enteric coated tablets (ECT), orally, twice daily (BID), on Days 1 to 7 followed by a 14-day rest period in 21-day cycles plus rituximab 375 mg/m^2, intravenous (IV), infusion on Day 1 of each 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 30 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1, plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 40 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 50 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Overall Number of Participants Analyzed 13 4 25 3
Mean (Standard Deviation)
Unit of Measure: nanoMolar (nM)
Day 1 Number Analyzed 13 participants 4 participants 25 participants 3 participants
1624.1  (929.68) 893.3  (350.03) 1159.7  (391.78) 1746.7  (594.75)
Day 7 Number Analyzed 12 participants 4 participants 20 participants 2 participants
2915.8  (1537.03) 1672.5  (183.92) 2223.3  (1217.22) 3670.0  (1541.49)
18.Secondary Outcome
Title Tmax: Time to First Occurrence of Cmax fo Alisertib
Hide Description [Not Specified]
Time Frame Cycle 1 Days 1 and 7 prior to morning alisertib dose and multiple time-points (up to 12 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Alisertib PK-Evaluable Population was defined as all participants with sufficient dosing and alisertib concentration-time data to permit non-compartmental PK analysis. Number analyzed is the number of participants with data available at the given time-point.
Arm/Group Title Safety Lead-in Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg
Hide Arm/Group Description:
Alisertib 50 mg, enteric coated tablets (ECT), orally, twice daily (BID), on Days 1 to 7 followed by a 14-day rest period in 21-day cycles plus rituximab 375 mg/m^2, intravenous (IV), infusion on Day 1 of each 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 30 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1, plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 40 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 50 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Overall Number of Participants Analyzed 13 4 25 3
Median (Full Range)
Unit of Measure: hours (hr)
Day 1 Number Analyzed 13 participants 4 participants 25 participants 3 participants
3.0
(2 to 8)
3.5
(3 to 6)
3.0
(1 to 12)
6.1
(3 to 12)
Day 7 Number Analyzed 12 participants 4 participants 20 participants 2 participants
2.0
(0 to 8)
3.1
(2 to 6)
3.1
(2 to 8)
2.5
(2 to 3)
19.Secondary Outcome
Title AUCt: Area Under the Concentration Time Curve Over the Dosing Interval From Time 0 to Time t for Alisertib
Hide Description [Not Specified]
Time Frame Cycle 1 Days 1 and 7 prior to morning alisertib dose and multiple time-points (up to 12 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Alisertib PK-Evaluable Population was defined as all participants with sufficient dosing and alisertib concentration-time data to permit non-compartmental PK analysis. Number analyzed is the number of participants with data available at the given time-point.
Arm/Group Title Safety Lead-in Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg
Hide Arm/Group Description:
Alisertib 50 mg, enteric coated tablets (ECT), orally, twice daily (BID), on Days 1 to 7 followed by a 14-day rest period in 21-day cycles plus rituximab 375 mg/m^2, intravenous (IV), infusion on Day 1 of each 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 30 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1, plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 40 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 50 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Overall Number of Participants Analyzed 13 4 25 3
Mean (Standard Deviation)
Unit of Measure: nanomoles/liter*hour (nmol/L*hr)
Day 1 Number Analyzed 12 participants 4 participants 22 participants 3 participants
10116.7  (6683.97) 5817.5  (2966.26) 8005.9  (3251.32) 13096.7  (7453.39)
Day 7 Number Analyzed 12 participants 4 participants 20 participants 2 participants
21812.5  (13090.21) 12227.5  (3480.09) 17996.0  (11555.15) 33800.0  (16263.46)
20.Secondary Outcome
Title Cmax: Maximum Plasma Concentration for Vincristine
Hide Description [Not Specified]
Time Frame Cycles 1 and 2 on Day 1 prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Vincristine PK-evaluable population was defined as all participants with sufficient dosing and vincristine concentration-time data to permit non-compartmental PK analysis. Safety Lead-in arm did not receive vincristine. Number analyzed is the number of participants with data available at the given time-point.
Arm/Group Title Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg
Hide Arm/Group Description:
Alisertib 30 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1, plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 40 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 50 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Overall Number of Participants Analyzed 4 25 3
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cycle 1, Day 1 Number Analyzed 4 participants 25 participants 3 participants
132.2  (54.57) 105.4  (78.93) 158.4  (67.94)
Cycle 2, Day 1 Number Analyzed 4 participants 17 participants 2 participants
113.9  (53.86) 124.4  (157.70) 122.3  (36.42)
21.Secondary Outcome
Title AUCt: Area Under the Concentration-time Time Curve Over the Dosing Interval From Time 0 to Time t for Vincristine
Hide Description [Not Specified]
Time Frame Cycles 1 and 2 on Day 1 prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Vincristine PK-evaluable population was defined as all participants with sufficient dosing and vincristine concentration-time data to permit non-compartmental PK analysis. Safety Lead-in arm did not receive vincristine Number analyzed is the number of participants with data available at the given time-point.
Arm/Group Title Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg
Hide Arm/Group Description:
Alisertib 30 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1, plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 40 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 50 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Overall Number of Participants Analyzed 4 24 3
Mean (Standard Deviation)
Unit of Measure: ng/mL*hr
Cycle 1, Day 1 Number Analyzed 4 participants 24 participants 3 participants
69.8  (9.92) 69.1  (33.24) 104.1  (43.34)
Cycle 2, Day 1 Number Analyzed 2 participants 17 participants 2 participants
60.8  (2.26) 72.8  (30.40) 72.2  (32.60)
22.Secondary Outcome
Title AUC∞: Area Under the Concentration-time Curve From Time 0 to Infinity for Vincristine
Hide Description [Not Specified]
Time Frame Cycles 1 and 2 on Day 1 prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Vincristine PK-evaluable population was defined as participants with sufficient dosing and concentration-time data to permit non-compartmental PK analysis. Safety Lead-in arm did not receive vincristine. Number analyzed is the number of participants with data available at the time-point. No data was collected for the alisertib 50 mg arm in Cycle 2.
Arm/Group Title Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg
Hide Arm/Group Description:
Alisertib 30 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1, plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 40 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 50 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Overall Number of Participants Analyzed 4 22 3
Mean (Standard Deviation)
Unit of Measure: ng/mL*hr
Cycle 1, Day 1 Number Analyzed 4 participants 22 participants 3 participants
77.9  (11.25) 84.8  (36.21) 116.8  (44.95)
Cycle 2, Day 1 Number Analyzed 3 participants 16 participants 0 participants
69.0  (4.45) 82.7  (35.39)
23.Secondary Outcome
Title T1/2: Terminal Disposition Phase Half-life for Vincristine
Hide Description [Not Specified]
Time Frame Cycles 1 and 2 on Day prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Vincristine PK-evaluable population was defined as participants with sufficient dosing and concentration-time data to permit non-compartmental PK analysis. Safety Lead-in arm did not receive vincristine. Number analyzed is the number of participants with data available at the time-point. No data was collected for the alisertib 50 mg arm in Cycle 2.
Arm/Group Title Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg
Hide Arm/Group Description:
Alisertib 30 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1, plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 40 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Alisertib 50 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
Overall Number of Participants Analyzed 4 25 3
Mean (Standard Deviation)
Unit of Measure: nanogram/milliliter (ng/mL)
Cycle 1, Day 1 Number Analyzed 4 participants 22 participants 3 participants
20.2  (5.04) 20.0  (5.89) 25.6  (4.55)
Cycle 2, Day 1 Number Analyzed 3 participants 16 participants 0 participants
19.9  (0.92) 20.2  (4.66)
Time Frame First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
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.
 
Arm/Group Title Safety Lead-in Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg
Hide Arm/Group Description Alisertib 50 mg, enteric coated tablets (ECT), orally, twice daily (BID), on Days 1 to 7 followed by a 14-day rest period in 21-day cycles plus rituximab 375 mg/m^2, intravenous (IV), infusion on Day 1 of each 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years. Alisertib 30 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1, plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years. Alisertib 40 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years. Alisertib 50 mg, ECT, orally, BID, on Days 1 to 7 followed by a 14-day rest period plus rituximab 375 mg/m^2, IV, infusion on Day 1 plus vincristine 1.4 mg/m^2, IV (max 2 mg), on Days 1 and 8 in a 21-day cycle for up to 8 cycles. Following 8 cycles of treatment (or early discontinuation of rituximab and/or vincristine) all participants with documented disease response or stabilization may continue with alisertib single-agent therapy for up to 2 years.
All-Cause Mortality
Safety Lead-in Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Safety Lead-in Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/13 (46.15%)   1/4 (25.00%)   12/25 (48.00%)   3/3 (100.00%) 
Blood and lymphatic system disorders         
Febrile neutropenia  1  0/13 (0.00%)  0/4 (0.00%)  3/25 (12.00%)  3/3 (100.00%) 
Neutropenia  1  0/13 (0.00%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Anaemia  1  2/13 (15.38%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Thrombocytopenia  1  0/13 (0.00%)  0/4 (0.00%)  0/25 (0.00%)  1/3 (33.33%) 
Cardiac disorders         
Myocardial infarction  1  0/13 (0.00%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Gastrointestinal disorders         
Diarrhoea  1  0/13 (0.00%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Stomatitis  1  0/13 (0.00%)  0/4 (0.00%)  0/25 (0.00%)  2/3 (66.67%) 
Upper gastrointestinal haemorrhage  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Ascites  1  0/13 (0.00%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Abdominal pain  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
General disorders         
Pyrexia  1  2/13 (15.38%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Asthenia  1  0/13 (0.00%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Fatigue  1  0/13 (0.00%)  0/4 (0.00%)  0/25 (0.00%)  1/3 (33.33%) 
Infections and infestations         
Sepsis  1  0/13 (0.00%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Septic shock  1 [1]  0/13 (0.00%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Clostridium difficile colitis  1  0/13 (0.00%)  0/4 (0.00%)  0/25 (0.00%)  1/3 (33.33%) 
Enterobacter bacteraemia  1  0/13 (0.00%)  0/4 (0.00%)  0/25 (0.00%)  1/3 (33.33%) 
Herpes zoster  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Klebsiella bacteraemia  1  0/13 (0.00%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Pneumonia  1  0/13 (0.00%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Soft tissue infection  1  0/13 (0.00%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Metabolism and nutrition disorders         
Hypercalcaemia  1  0/13 (0.00%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Hypokalaemia  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Myelodysplastic syndrome  1  0/13 (0.00%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Spinal cord neoplasm  1  0/13 (0.00%)  1/4 (25.00%)  0/25 (0.00%)  0/3 (0.00%) 
Malignant pleural effusion  1  0/13 (0.00%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Nervous system disorders         
Spinal cord compression  1  0/13 (0.00%)  1/4 (25.00%)  0/25 (0.00%)  0/3 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Dyspnoea  1  2/13 (15.38%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Tachypnoea  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Pulmonary embolism  1  1/13 (7.69%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Respiratory failure  1 [2]  1/13 (7.69%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Pleural effusion  1 [3]  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Vascular disorders         
Hypotension  1  0/13 (0.00%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Orthostatic hypotension  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
[1]
One treatment-emergent death occurred during treatment with alisertib 40 mg BID and is not related.
[2]
Two treatment-emergent deaths occurred during treatment with alisertib 50 mg BID and alisertib 40 mg BID and are not related.
[3]
One treatment-emergent death occurred during treatment with 50 mg BID and is not related.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Safety Lead-in Dose Escalation, Alisertib 30 mg Dose Escalation, Alisertib 40 mg Dose Escalation, Alisertib 50 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/13 (100.00%)   4/4 (100.00%)   25/25 (100.00%)   3/3 (100.00%) 
Blood and lymphatic system disorders         
Anaemia  1  6/13 (46.15%)  3/4 (75.00%)  15/25 (60.00%)  2/3 (66.67%) 
Leukopenia  1  8/13 (61.54%)  2/4 (50.00%)  9/25 (36.00%)  3/3 (100.00%) 
Neutropenia  1  7/13 (53.85%)  2/4 (50.00%)  11/25 (44.00%)  2/3 (66.67%) 
Thrombocytopenia  1  7/13 (53.85%)  1/4 (25.00%)  8/25 (32.00%)  3/3 (100.00%) 
Lymphopenia  1  2/13 (15.38%)  2/4 (50.00%)  1/25 (4.00%)  1/3 (33.33%) 
Pancytopenia  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Cardiac disorders         
Pericardial effusion  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Ear and labyrinth disorders         
Ear discomfort  1  0/13 (0.00%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Deafness unilateral  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Vertigo  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Eye disorders         
Vision blurred  1  1/13 (7.69%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Ocular icterus  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Gastrointestinal disorders         
Diarrhoea  1  4/13 (30.77%)  0/4 (0.00%)  16/25 (64.00%)  0/3 (0.00%) 
Nausea  1  1/13 (7.69%)  1/4 (25.00%)  14/25 (56.00%)  1/3 (33.33%) 
Constipation  1  2/13 (15.38%)  1/4 (25.00%)  9/25 (36.00%)  1/3 (33.33%) 
Stomatitis  1  2/13 (15.38%)  0/4 (0.00%)  6/25 (24.00%)  1/3 (33.33%) 
Vomiting  1  1/13 (7.69%)  1/4 (25.00%)  6/25 (24.00%)  1/3 (33.33%) 
Abdominal pain  1  3/13 (23.08%)  0/4 (0.00%)  4/25 (16.00%)  0/3 (0.00%) 
Dyspepsia  1  0/13 (0.00%)  0/4 (0.00%)  3/25 (12.00%)  1/3 (33.33%) 
Abdominal distension  1  0/13 (0.00%)  0/4 (0.00%)  3/25 (12.00%)  0/3 (0.00%) 
Dysphagia  1  1/13 (7.69%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Gastrooesophageal reflux disease  1  0/13 (0.00%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Haemorrhoids  1  2/13 (15.38%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Oral pain  1  1/13 (7.69%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Proctalgia  1  0/13 (0.00%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Aphthous ulcer  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Hypoaesthesia oral  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Oral discomfort  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Paraesthesia oral  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Tongue ulceration  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Toothache  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
General disorders         
Fatigue  1  4/13 (30.77%)  2/4 (50.00%)  11/25 (44.00%)  2/3 (66.67%) 
Chills  1  2/13 (15.38%)  0/4 (0.00%)  3/25 (12.00%)  0/3 (0.00%) 
Oedema peripheral  1  1/13 (7.69%)  1/4 (25.00%)  3/25 (12.00%)  0/3 (0.00%) 
Asthenia  1  1/13 (7.69%)  1/4 (25.00%)  1/25 (4.00%)  0/3 (0.00%) 
Pyrexia  1  1/13 (7.69%)  0/4 (0.00%)  1/25 (4.00%)  1/3 (33.33%) 
Early satiety  1  0/13 (0.00%)  0/4 (0.00%)  1/25 (4.00%)  1/3 (33.33%) 
Peripheral swelling  1  0/13 (0.00%)  0/4 (0.00%)  1/25 (4.00%)  1/3 (33.33%) 
Adverse drug reaction  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Infusion site erythema  1  0/13 (0.00%)  0/4 (0.00%)  0/25 (0.00%)  1/3 (33.33%) 
Injection site pain  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Pain  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Temperature regulation disorder  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Infections and infestations         
Urinary tract infection  1  1/13 (7.69%)  0/4 (0.00%)  6/25 (24.00%)  2/3 (66.67%) 
Upper respiratory tract infection  1  1/13 (7.69%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Bronchitis  1  0/13 (0.00%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Nasopharyngitis  1  1/13 (7.69%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Sinusitis  1  1/13 (7.69%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Tooth infection  1  1/13 (7.69%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Diverticulitis  1  0/13 (0.00%)  1/4 (25.00%)  0/25 (0.00%)  0/3 (0.00%) 
Otitis media  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Pharyngitis  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Pharyngitis bacterial  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Injury, poisoning and procedural complications         
Infusion related reaction  1  0/13 (0.00%)  0/4 (0.00%)  3/25 (12.00%)  1/3 (33.33%) 
Fall  1  1/13 (7.69%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Head Injury  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Investigations         
Neutrophil count decreased  1  1/13 (7.69%)  0/4 (0.00%)  3/25 (12.00%)  1/3 (33.33%) 
Aspartate aminotransferase increased  1  0/13 (0.00%)  0/4 (0.00%)  1/25 (4.00%)  2/3 (66.67%) 
Platelet count decreased  1  1/13 (7.69%)  0/4 (0.00%)  1/25 (4.00%)  1/3 (33.33%) 
Weight decreased  1  1/13 (7.69%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Alanine aminotransferase increased  1  0/13 (0.00%)  0/4 (0.00%)  0/25 (0.00%)  2/3 (66.67%) 
Electrocardiogram QT prolonged  1  2/13 (15.38%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Blood bilirubin increased  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Lymphocyte count decreased  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
White blood cell count decreased  1  0/13 (0.00%)  0/4 (0.00%)  0/25 (0.00%)  1/3 (33.33%) 
Metabolism and nutrition disorders         
Decreased appetite  1  3/13 (23.08%)  1/4 (25.00%)  7/25 (28.00%)  1/3 (33.33%) 
Hypokalaemia  1  4/13 (30.77%)  0/4 (0.00%)  6/25 (24.00%)  2/3 (66.67%) 
Hypomagnesaemia  1  2/13 (15.38%)  0/4 (0.00%)  5/25 (20.00%)  1/3 (33.33%) 
Hyperglycaemia  1  1/13 (7.69%)  1/4 (25.00%)  2/25 (8.00%)  1/3 (33.33%) 
Hypoalbuminaemia  1  3/13 (23.08%)  0/4 (0.00%)  0/25 (0.00%)  2/3 (66.67%) 
Dehydration  1  0/13 (0.00%)  0/4 (0.00%)  4/25 (16.00%)  0/3 (0.00%) 
Hypocalcaemia  1  2/13 (15.38%)  0/4 (0.00%)  1/25 (4.00%)  1/3 (33.33%) 
Hyponatraemia  1  2/13 (15.38%)  0/4 (0.00%)  0/25 (0.00%)  1/3 (33.33%) 
Hypophosphataemia  1  1/13 (7.69%)  0/4 (0.00%)  1/25 (4.00%)  1/3 (33.33%) 
Hypercalcaemia  1  1/13 (7.69%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Hypermagnesaemia  1  0/13 (0.00%)  0/4 (0.00%)  0/25 (0.00%)  1/3 (33.33%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  0/13 (0.00%)  1/4 (25.00%)  3/25 (12.00%)  1/3 (33.33%) 
Myalgia  1  2/13 (15.38%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Arthralgia  1  0/13 (0.00%)  0/4 (0.00%)  3/25 (12.00%)  0/3 (0.00%) 
Musculoskeletal pain  1  1/13 (7.69%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Bone pain  1  0/13 (0.00%)  0/4 (0.00%)  1/25 (4.00%)  1/3 (33.33%) 
Flank pain  1  2/13 (15.38%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Muscle spasms  1  0/13 (0.00%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Musculoskeletal chest pain  1  0/13 (0.00%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Neck pain  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Pain in jaw  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Nervous system disorders         
Dizziness  1  2/13 (15.38%)  1/4 (25.00%)  6/25 (24.00%)  1/3 (33.33%) 
Headache  1  1/13 (7.69%)  1/4 (25.00%)  5/25 (20.00%)  0/3 (0.00%) 
Neuropathy peripheral  1  0/13 (0.00%)  2/4 (50.00%)  3/25 (12.00%)  0/3 (0.00%) 
Peripheral sensory neuropathy  1  0/13 (0.00%)  0/4 (0.00%)  4/25 (16.00%)  1/3 (33.33%) 
Somnolence  1  5/13 (38.46%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Paraesthesia  1  0/13 (0.00%)  1/4 (25.00%)  2/25 (8.00%)  0/3 (0.00%) 
Aphasia  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Neuralgia  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Tongue paralysis  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Psychiatric disorders         
Insomnia  1  1/13 (7.69%)  0/4 (0.00%)  4/25 (16.00%)  0/3 (0.00%) 
Anxiety  1  0/13 (0.00%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Depression  1  1/13 (7.69%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Confusional state  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Mental status changes  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Personality change  1  0/13 (0.00%)  1/4 (25.00%)  0/25 (0.00%)  0/3 (0.00%) 
Renal and urinary disorders         
Hydronephrosis  1  1/13 (7.69%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Urinary incontinence  1  1/13 (7.69%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Dysuria  1  0/13 (0.00%)  1/4 (25.00%)  0/25 (0.00%)  0/3 (0.00%) 
Hydroureter  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Nocturia  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Reproductive system and breast disorders         
Prostatitis  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Vaginal ulceration  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Dyspnoea  1  1/13 (7.69%)  0/4 (0.00%)  7/25 (28.00%)  0/3 (0.00%) 
Cough  1  2/13 (15.38%)  0/4 (0.00%)  3/25 (12.00%)  0/3 (0.00%) 
Oropharyngeal pain  1  2/13 (15.38%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Dysphonia  1  1/13 (7.69%)  0/4 (0.00%)  1/25 (4.00%)  1/3 (33.33%) 
Epistaxis  1  0/13 (0.00%)  1/4 (25.00%)  2/25 (8.00%)  0/3 (0.00%) 
Nasal congestion  1  0/13 (0.00%)  0/4 (0.00%)  3/25 (12.00%)  0/3 (0.00%) 
Nasal ulcer  1  0/13 (0.00%)  0/4 (0.00%)  0/25 (0.00%)  1/3 (33.33%) 
Pharyngeal inflammation  1  0/13 (0.00%)  0/4 (0.00%)  0/25 (0.00%)  1/3 (33.33%) 
Pleural effusion  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Sneezing  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Skin and subcutaneous tissue disorders         
Alopecia  1  3/13 (23.08%)  1/4 (25.00%)  5/25 (20.00%)  0/3 (0.00%) 
Pruritus  1  2/13 (15.38%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Rash maculo-papular  1  1/13 (7.69%)  0/4 (0.00%)  3/25 (12.00%)  0/3 (0.00%) 
Rash macular  1  1/13 (7.69%)  1/4 (25.00%)  0/25 (0.00%)  1/3 (33.33%) 
Palmar-plantar erythrodysaesthesia syndrome  1  0/13 (0.00%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Rash  1  2/13 (15.38%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Rash erythematous  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  1/3 (33.33%) 
Vascular disorders         
Hypotension  1  0/13 (0.00%)  0/4 (0.00%)  2/25 (8.00%)  1/3 (33.33%) 
Orthostatic hypotension  1  1/13 (7.69%)  2/4 (50.00%)  0/25 (0.00%)  0/3 (0.00%) 
Deep vein thrombosis  1  0/13 (0.00%)  0/4 (0.00%)  2/25 (8.00%)  0/3 (0.00%) 
Thrombophlebitis superficial  1  1/13 (7.69%)  0/4 (0.00%)  1/25 (4.00%)  0/3 (0.00%) 
Hypertension  1  1/13 (7.69%)  0/4 (0.00%)  0/25 (0.00%)  0/3 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
The Phase 2 portion of the study was cancelled by the sponsor; this was an administrative decision not based on any clinical or safety outcomes.
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.
In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor’s confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
Results Point of Contact
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
Responsible Party: Takeda ( Millennium Pharmaceuticals, Inc. )
ClinicalTrials.gov Identifier: NCT01397825     History of Changes
Other Study ID Numbers: C14011
2011-000609-32 ( EudraCT Number )
U1111-1181-0333 ( Registry Identifier: WHO )
12/NE/0268 ( Registry Identifier: NRES )
First Submitted: July 17, 2011
First Posted: July 20, 2011
Results First Submitted: January 4, 2018
Results First Posted: March 27, 2018
Last Update Posted: March 27, 2018