MLN8237 in Patients With Relapsed or Refractory Aggressive B-Cell Lymphoma Treated With Rituximab +/- Vincristine
Sponsor
Millennium Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01397825
Collaborator
(none)
45
25
5
61.9
1.8
0
Study Details
Study Description
Brief Summary
This is a single-arm, open-label, multicenter, dose escalation, phase 1-2 study of alisertib (MLN8237) administered in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL)/transformed follicular lymphoma (TFL) treated with rituximab and vincristine. The study has three parts as follows:
Phase 1, Part 1: Safety lead-in cohort to evaluate alisertib (MLN8237) and rituximab.
Phase 1, Part 2: Dose escalation cohort to evaluate alisertib (MLN8237) + Rituximab + Vincristine and determine Phase 2 dose. Patients with other types of B-cell lymphoma (including mantle cell or Burkitt's lymphoma may enroll in Parts 1 and 2.
Phase 2: Alisertib (MLN8237) + Rituximab + Vincristine in patients with relapsed or refractory DLBCL or TFL at recommended Phase 2 dose.
Note that in 2013 Sponsor decision was taken to not initiate the phase 2 portion of the trial, which would have investigated the triplet at the recommended phase 2 dose identified in part 2. This decision was based on reprioritization within the company and not on any clinical or safety outcomes observed.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
The drug tested in this study was called alisertib. Alisertib was tested to treat people who have relapsed or refractory diffuse large B-cell lymphoma or other aggressive B-cell lymphomas. This study looked at safety, any anti-tumor effect, and it also determined a recommended dose of alisertib plus rituximab and alisertib plus rituximab and vincristine to take into further studies. Pharmacokinetic blood samples were studied to characterize any effects on the concentration of each of the drugs when administered together .
The study enrolled 45 patients. Participants received the following treatments:
Phase 1
-
Alisertib 50 mg + rituximab in the Safety Lead-in
-
Alisertib 30 mg + rituximab + vincristine in the Dose Escalation
-
Alisertib 40 mg + rituximab + vincristine in the Dose Escalation
-
Alisertib 50 mg + rituximab + vincristine in the Dose Escalation
All participants were asked to take one alisertib table twice a day for 7 days in each cycle for up to 8 cycles along with rituximab on Day 1 of each cycle; some patients also received vincristine on Day 1 and Day 8 of each cycle. All participants with documented disease response or stabilization could continue with alisertib single-agent therapy for an additional 2 years or more.
This multi-center trial was conducted in the USA. The overall time to participate in this study was up to 5.2 years. Participants made multiple visits to the clinic, plus a final visit 30 days after receiving their last dose of study drug for a follow-up assessment.
Study Design
Study Type:
Interventional
Actual Enrollment
:
45 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Phase 1-2 Study of MLN8237, an Oral Aurora A Kinase Inhibitor, in Patients With Relapsed or Refractory Aggressive B-Cell Lymphoma Treated With Rituximab and Vincristine
Actual Study Start Date
:
Aug 9, 2011
Actual Primary Completion Date
:
Feb 5, 2015
Actual Study Completion Date
:
Oct 5, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Safety Lead-in 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. |
Drug: Alisertib (MLN8237)
Alisertib (MLN8237) enteric coated tablet (ECT).
Drug: Rituximab
Rituximab IV infusion.
|
| Experimental: Dose Escalation, Alisertib 30 mg 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 (max 2 mg), IV, 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. |
Drug: Alisertib (MLN8237)
Alisertib (MLN8237) enteric coated tablet (ECT).
Drug: Rituximab
Rituximab IV infusion.
Drug: Vincristine
Vincristine IV Infusion.
|
| Experimental: Dose Escalation, Alisertib 40 mg 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 2mg), 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. |
Drug: Alisertib (MLN8237)
Alisertib (MLN8237) enteric coated tablet (ECT).
Drug: Rituximab
Rituximab IV infusion.
Drug: Vincristine
Vincristine IV Infusion.
|
| Experimental: Dose Escalation, Alisertib 50 mg 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 2mg), 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. |
Drug: Alisertib (MLN8237)
Alisertib (MLN8237) enteric coated tablet (ECT).
Drug: Rituximab
Rituximab IV infusion.
Drug: Vincristine
Vincristine IV Infusion.
|
| Experimental: Phase 2: Alisertib 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. |
Drug: Alisertib (MLN8237)
Alisertib (MLN8237) enteric coated tablet (ECT).
Drug: Rituximab
Rituximab IV infusion.
Drug: Vincristine
Vincristine IV Infusion.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Clinically Significant Vital Signs Findings (Treatment Related and Unrelated) [Phase 1] [First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)]
Vital sign parameters: blood pressure, heart rate and temperature determined by the investigator to be clinically significant were reported as adverse events.
- Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs) [Phase 1] [First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)]
Abnormal ECGs findings determined by the investigator to be clinically significant were reported as adverse events.
- Number of Participants With Clinically Significant Changes in Multigated Acquisition (MUGA)/ Echocardiogram (ECHO) [Phase 1] [First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)]
Abnormal changes in MUGA and ECHO findings determined by the investigator to be clinically significant were reported as adverse events.
- Number of Participants With Clinically Significant Changes in Physical Examination Findings [Phase 1] [First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)]
Abnormal Physical Examination findings determined by the investigator to be clinically significant were reported as Adverse Events.
- Number of Participants With Clinically Significant Laboratory Tests Reported as Adverse Events [Phase 1] [First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)]
Abnormal treatment-emergent Chemistry and Hematology Laboratory values determined by the investigator to be clinically significant were reported as adverse events.
- Number of Participants With Treatment-Emergent Adverse Events [Phase 1] [First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)]
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.
- Overall Response Rate [Phase 2] [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]
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.
Secondary Outcome Measures
- Overall Response Rate as Assessed by the Investigator [Phase 1] [First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)]
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.
- Complete Response Rate [Phase 2] [Duration of study until disease progression, approximately 2 years]
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.
- Duration of Response (DOR) [Phase 2] [Duration of study until disease progression, approximately 2 years]
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).
- Progression Free Survival (PFS) [Phase 2] [Duration of study until disease progression, approximately 2 years]
PFS was defined as the time from the date of first study drug administration to the date of first documentation of PD or death.
- Number of Participants With Treatment-Emergent Adverse Events [Phase 2] [From screening period to 30 days after last dose of study drug, approximately 2 years]
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.
- Number of Participants With Clinically Significant Vital Signs Findings [Phase 2] [From screening period to 30 days after last dose of study drug, approximately 2 years]
Vital sign parameters: blood pressure, heart rate and temperature determined by the investigator to be clinically significant were reported as adverse events.
- Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs) [Phase 2] [From screening period to 30 days after last dose of study drug, approximately 2 years]
- Number of Participants With Clinically Significant Changes in Multigated Acquisition (MUGA)/ Echocardiogram (ECHO) [Phase 2] [From screening period to 30 days after last dose of study drug, approximately 2 years]
- Number of Participants With Clinically Significant Laboratory Tests Reported as Adverse Events [Phase 2] [From screening period to 30 days after last dose of study drug, approximately 2 years]
- Cmax: Maximum Plasma Concentration for Alisertib [Cycle 1 Days 1 and 7 prior to morning alisertib dose and multiple time-points (up to 12 hours) post-dose]
- Tmax: Time to First Occurrence of Cmax fo Alisertib [Cycle 1 Days 1 and 7 prior to morning alisertib dose and multiple time-points (up to 12 hours) post-dose]
- AUCt: Area Under the Concentration Time Curve Over the Dosing Interval From Time 0 to Time t for Alisertib [Cycle 1 Days 1 and 7 prior to morning alisertib dose and multiple time-points (up to 12 hours) post-dose]
- Cmax: Maximum Plasma Concentration for Vincristine [Cycles 1 and 2 on Day 1 prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose]
- AUCt: Area Under the Concentration-time Time Curve Over the Dosing Interval From Time 0 to Time t for Vincristine [Cycles 1 and 2 on Day 1 prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose]
- AUC∞: Area Under the Concentration-time Curve From Time 0 to Infinity for Vincristine [Cycles 1 and 2 on Day 1 prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose]
- T1/2: Terminal Disposition Phase Half-life for Vincristine [Cycles 1 and 2 on Day prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL)/transformed follicular lymphoma (TFL). Note: Patients with Mantle Cell or Burkitt's lymphoma may be eligible for enrollment to the safety lead-in and dose escalation cohorts, parts 1 & 2 only
-
Relapsed or refractory after at least 1 prior systemic treatment for aggressive lymphoma (including anthracycline unless contra-indicated). Relapse following an autologous stem cell transplant is allowed.
-
Relapsed after autologous stem cell transplantation or not be eligible for autologous stem cell transplantation or refuse autologous stem cell transplantation. Patients enrolled to the phase 2 part must have received prior rituximab.
-
Measurable disease as specified in study protocol
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
-
Female patients who are post menopausal for at least 1 year, surgically sterile, or agree to practice 2 effective methods of contraception through 30 days after the last dose of alisertib (MLN8237) or agree to abstain from heterosexual intercourse. Patients should also use effective contraception for 12 months following the last dose of rituximab and 1 month following the last dose of alisertib (MLN8237.
-
Male patients who agree to practice effective barrier contraception through 4 months after the last dose of MLN8237 or agree to abstain from heterosexual intercourse
-
Voluntary written consent
Exclusion Criteria
-
Received more than 4 prior systemic treatment regimens for lymphoma
-
Known human immunodeficiency virus (HIV) positive or acquired immunodeficiency syndrome (AIDS)-related illness; hepatitis B virus, or hepatitis C virus; known history of Charcot-Marie-Tooth disease or polio
-
Autologous stem cell transplant less than 3 months prior to enrollment
-
Patients who have undergone allogeneic stem cell or organ transplantation any time
-
Systemic antineoplastic therapy, including glucocorticoids or treatment with an investigational agent within 14 days preceding the first dose of study drug treatment. Steroids are permitted for administration with rituximab to prevent or treat infusion reaction
-
Treatment with nitrosoureas, mitomycin C, rituximab, alemtuzumab, or other unconjugated antibody treatment within 42 days (21 days if clear evidence of progressive disease) prior to the first day of study drug treatment
-
Treatment with radioimmunoconjugates or toxin immunoconjugates, such as ibritumomab-tiuxetan, or tositumomab, within 12 weeks prior to the first day of study drug treatment
-
Radiotherapy within 21 days prior to the first dose of study drug treatment
-
Treatment with enzyme-inducing antiepileptic drugs, such as phenytoin, carbamazepine, or phenobarbital, or with rifampin, rifabutin, rifapentine, or St. John's wort, within 14 days prior to the first dose of alisertib (MLN8237) also not permitted during study
-
Cardiac status as described in protocol
-
Major surgery, serious infection, or infection requiring systemic antibiotic therapy within 14 days prior to the first dose of study treatment
-
History of hemorrhagic or thrombotic cerebrovascular event in the past 12 months
-
Clinically uncontrolled central nervous system involvement
-
Inability to receive IV rituximab or vincristine, or to swallow tablets or inability or unwillingness to avoid taking anything by mouth except for water and prescribed medications for 2 hours before and 1 hour after each dose of alisertib (MLN8237)
-
History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness
-
Female patients who are lactating or pregnant
-
Serious medical or psychiatric illness or laboratory abnormality that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol
-
Clinically apparent ≥ Grade 2 neuropathy due to any cause in the 3 months prior to enrollment, or history of ≥ Grade 3 neuropathy related to vincristine at any time
-
Prior treatment with Aurora A-targeted agents, including alisertib (MLN8237)
-
Patients who have received myeloid growth factors or platelet transfusion within 14 days prior to the first dose of study treatment
-
Patients with known hypersensitivity to rituximab, vincristine (or vinca alkaloids), or their diluents
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tucson | Arizona | United States | ||
| 2 | Beverly Hills | California | United States | ||
| 3 | Burbank | California | United States | ||
| 4 | Miami | Florida | United States | ||
| 5 | Lexington | Kentucky | United States | ||
| 6 | Worcester | Massachusetts | United States | ||
| 7 | New York | New York | United States | ||
| 8 | Rochester | New York | United States | ||
| 9 | Chapel Hill | North Carolina | United States | ||
| 10 | Philadelphia | Pennsylvania | United States | ||
| 11 | Germantown | Tennessee | United States | ||
| 12 | Memphis | Tennessee | United States | ||
| 13 | Houston | Texas | United States | ||
| 14 | San Antonio | Texas | United States | ||
| 15 | Burlington | Vermont | United States | ||
| 16 | Orbassano | Torino | Italy | ||
| 17 | Genova | Italy | |||
| 18 | Palermo | Italy | |||
| 19 | Roma | Italy | |||
| 20 | Madrid | Spain | |||
| 21 | Sevilla | Spain | |||
| 22 | Aberdeen | Grampian Region | United Kingdom | ||
| 23 | London | Greater London | United Kingdom | ||
| 24 | Southampton | Hampshire | United Kingdom | ||
| 25 | Birmingham | West Midlands | United Kingdom |
Sponsors and Collaborators
- Millennium Pharmaceuticals, Inc.
Investigators
- Study Director: Medical Monitor, Millennium Pharmaceuticals, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01397825
Other Study ID Numbers:
- C14011
- 2011-000609-32
- U1111-1181-0333
- 12/NE/0268
First Posted:
Jul 20, 2011
Last Update Posted:
Mar 27, 2018
Last Verified:
Feb 1, 2018
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| 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 Detail | 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 |
|---|---|---|---|---|---|
| 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 |
Baseline Characteristics
| Arm/Group Title | Safety Lead-in | Dose Escalation, Alisertib 30 mg | Dose Escalation, Alisertib 40 mg | Dose Escalation, Alisertib 50 mg | Total |
|---|---|---|---|---|---|
| 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 Participants | 13 | 4 | 25 | 3 | 45 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
60.3
(14.06)
|
51.3
(21.65)
|
62.8
(10.51)
|
66.7
(12.86)
|
61.3
(12.89)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
3
23.1%
|
1
25%
|
10
40%
|
2
66.7%
|
16
35.6%
|
| Male |
10
76.9%
|
3
75%
|
15
60%
|
1
33.3%
|
29
64.4%
|
| Race/Ethnicity, Customized (participants) [Number] | |||||
| Hispanic or Latino |
7
53.8%
|
1
25%
|
6
24%
|
1
33.3%
|
15
33.3%
|
| Not Hispanic or Latino |
6
46.2%
|
3
75%
|
19
76%
|
2
66.7%
|
30
66.7%
|
| Race/Ethnicity, Customized (participants) [Number] | |||||
| White |
12
92.3%
|
4
100%
|
21
84%
|
3
100%
|
40
88.9%
|
| Black or African American |
0
0%
|
0
0%
|
2
8%
|
0
0%
|
2
4.4%
|
| Asian |
1
7.7%
|
0
0%
|
0
0%
|
0
0%
|
1
2.2%
|
| Other |
0
0%
|
0
0%
|
1
4%
|
0
0%
|
1
2.2%
|
| Not Reported |
0
0%
|
0
0%
|
1
4%
|
0
0%
|
1
2.2%
|
| Region of Enrollment (participants) [Number] | |||||
| United States |
13
100%
|
4
100%
|
25
100%
|
3
100%
|
45
100%
|
| Height (cm) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [cm] |
167.9
(10.90)
|
178.2
(7.15)
|
168.4
(10.76)
|
166.5
(5.32)
|
169.0
(10.44)
|
| Weight (kg) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [kg] |
70.98
(16.18)
|
89.51
(23.89)
|
82.21
(16.4)
|
71.94
(14.55)
|
78.93
(17.46)
|
| Body Surface Area (m^2) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [m^2] |
1.815
(0.25)
|
2.093
(0.31)
|
1.940
(0.23)
|
1.823
(0.21)
|
1.910
(0.25)
|
Outcome Measures
| Title | Number of Participants With Clinically Significant Vital Signs Findings (Treatment Related and Unrelated) [Phase 1] |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 13 | 4 | 25 | 3 |
| Hypotension |
0
0%
|
0
0%
|
3
12%
|
1
33.3%
|
| Orthostatic hypotension |
2
15.4%
|
2
50%
|
0
0%
|
0
0%
|
| Hypertension |
1
7.7%
|
0
0%
|
0
0%
|
0
0%
|
| Pyrexia |
3
23.1%
|
0
0%
|
2
8%
|
1
33.3%
|
| Title | Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs) [Phase 1] |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 13 | 4 | 25 | 3 |
| Number [participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Clinically Significant Changes in Multigated Acquisition (MUGA)/ Echocardiogram (ECHO) [Phase 1] |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 13 | 4 | 25 | 3 |
| Number [participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Clinically Significant Changes in Physical Examination Findings [Phase 1] |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 13 | 4 | 25 | 3 |
| Number [participants] |
0
0%
|
0
0%
|
2
8%
|
2
66.7%
|
| Title | Number of Participants With Clinically Significant Laboratory Tests Reported as Adverse Events [Phase 1] |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 13 | 4 | 25 | 3 |
| Anaemia |
6
46.2%
|
3
75%
|
14
56%
|
2
66.7%
|
| Neutropenia |
7
53.8%
|
2
50%
|
11
44%
|
2
66.7%
|
| Febrile neutropenia |
0
0%
|
0
0%
|
4
16%
|
3
100%
|
| Leukopenia |
8
61.5%
|
2
50%
|
9
36%
|
3
100%
|
| Lymphopenia |
2
15.4%
|
2
50%
|
1
4%
|
1
33.3%
|
| Thrombocytopenia |
7
53.8%
|
1
25%
|
7
28%
|
3
100%
|
| Hypokalaemia |
5
38.5%
|
0
0%
|
6
24%
|
2
66.7%
|
| Hyperkalaemia |
0
0%
|
0
0%
|
1
4%
|
0
0%
|
| Hypomagnesaemia |
2
15.4%
|
0
0%
|
5
20%
|
1
33.3%
|
| Hypermagnesaemia |
0
0%
|
0
0%
|
0
0%
|
1
33.3%
|
| Hypocalcaemia |
2
15.4%
|
0
0%
|
1
4%
|
1
33.3%
|
| Hypercalcaemia |
1
7.7%
|
0
0%
|
2
8%
|
0
0%
|
| Hyperglycaemia |
1
7.7%
|
1
25%
|
2
8%
|
1
33.3%
|
| Hypoalbuminaemia |
3
23.1%
|
0
0%
|
0
0%
|
2
66.7%
|
| Hyponatraemia |
2
15.4%
|
0
0%
|
0
0%
|
1
33.3%
|
| Hypernatraemia |
0
0%
|
0
0%
|
1
4%
|
0
0%
|
| Hypophosphataemia |
1
7.7%
|
0
0%
|
1
4%
|
1
33.3%
|
| Neutrophil count decreased |
1
7.7%
|
0
0%
|
3
12%
|
1
33.3%
|
| Lymphocyte count decreased |
1
7.7%
|
0
0%
|
0
0%
|
0
0%
|
| White blood cell count decreased |
0
0%
|
0
0%
|
0
0%
|
1
33.3%
|
| Aspartate aminotransferase increased |
0
0%
|
0
0%
|
1
4%
|
2
66.7%
|
| Alanine aminotransferase increased |
0
0%
|
0
0%
|
0
0%
|
2
66.7%
|
| Blood bilirubin increased |
1
7.7%
|
0
0%
|
0
0%
|
0
0%
|
| Platelet count decreased |
1
7.7%
|
0
0%
|
1
4%
|
1
33.3%
|
| Title | Number of Participants With Treatment-Emergent Adverse Events [Phase 1] |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 13 | 4 | 25 | 3 |
| Number [participants] |
13
100%
|
4
100%
|
25
100%
|
3
100%
|
| Title | Overall Response Rate [Phase 2] |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Phase 2 portion of the study was cancelled by the sponsor. |
| Arm/Group Title | Phase 2: Alisertib |
|---|---|
| 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. |
| Measure Participants | 0 |
| Title | Overall Response Rate as Assessed by the Investigator [Phase 1] |
|---|---|
| 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) |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 12 | 3 | 20 | 2 |
| Number (95% Confidence Interval) [percentage of participants] |
25
192.3%
|
33
825%
|
45
180%
|
50
1666.7%
|
| Title | Complete Response Rate [Phase 2] |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Phase 2 portion of the study was cancelled by the sponsor. |
| Arm/Group Title | Phase 2: Alisertib |
|---|---|
| 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. |
| Measure Participants | 0 |
| Title | Duration of Response (DOR) [Phase 2] |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Phase 2 portion of the study was cancelled by the sponsor. |
| Arm/Group Title | Phase 2: Alisertib |
|---|---|
| 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. |
| Measure Participants | 0 |
| Title | Progression Free Survival (PFS) [Phase 2] |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Phase 2 portion of the study was cancelled by the sponsor. |
| Arm/Group Title | Phase 2: Alisertib |
|---|---|
| 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. |
| Measure Participants | 0 |
| Title | Number of Participants With Treatment-Emergent Adverse Events [Phase 2] |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Phase 2 portion of the study was cancelled by the sponsor. |
| Arm/Group Title | Phase 2: Alisertib |
|---|---|
| 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. |
| Measure Participants | 0 |
| Title | Number of Participants With Clinically Significant Vital Signs Findings [Phase 2] |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Phase 2 portion of the study was cancelled by the sponsor. |
| Arm/Group Title | Phase 2: Alisertib |
|---|---|
| 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. |
| Measure Participants | 0 |
| Title | Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs) [Phase 2] |
|---|---|
| Description | |
| Time Frame | From screening period to 30 days after last dose of study drug, approximately 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Phase 2 portion of the study was cancelled by the sponsor. |
| Arm/Group Title | Phase 2: Alisertib |
|---|---|
| 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. |
| Measure Participants | 0 |
| Title | Number of Participants With Clinically Significant Changes in Multigated Acquisition (MUGA)/ Echocardiogram (ECHO) [Phase 2] |
|---|---|
| Description | |
| Time Frame | From screening period to 30 days after last dose of study drug, approximately 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Phase 2 portion of the study was cancelled by the sponsor. |
| Arm/Group Title | Phase 2: Alisertib |
|---|---|
| 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. |
| Measure Participants | 0 |
| Title | Number of Participants With Clinically Significant Laboratory Tests Reported as Adverse Events [Phase 2] |
|---|---|
| Description | |
| Time Frame | From screening period to 30 days after last dose of study drug, approximately 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Phase 2 portion of the study was cancelled by the sponsor. |
| Arm/Group Title | Phase 2: Alisertib |
|---|---|
| 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. |
| Measure Participants | 0 |
| Title | Cmax: Maximum Plasma Concentration for Alisertib |
|---|---|
| Description | |
| Time Frame | Cycle 1 Days 1 and 7 prior to morning alisertib dose and multiple time-points (up to 12 hours) post-dose |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 13 | 4 | 25 | 3 |
| Day 1 |
1624.1
(929.68)
|
893.3
(350.03)
|
1159.7
(391.78)
|
1746.7
(594.75)
|
| Day 7 |
2915.8
(1537.03)
|
1672.5
(183.92)
|
2223.3
(1217.22)
|
3670.0
(1541.49)
|
| Title | Tmax: Time to First Occurrence of Cmax fo Alisertib |
|---|---|
| Description | |
| Time Frame | Cycle 1 Days 1 and 7 prior to morning alisertib dose and multiple time-points (up to 12 hours) post-dose |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 13 | 4 | 25 | 3 |
| Day 1 |
3.0
|
3.5
|
3.0
|
6.1
|
| Day 7 |
2.0
|
3.1
|
3.1
|
2.5
|
| Title | AUCt: Area Under the Concentration Time Curve Over the Dosing Interval From Time 0 to Time t for Alisertib |
|---|---|
| Description | |
| Time Frame | Cycle 1 Days 1 and 7 prior to morning alisertib dose and multiple time-points (up to 12 hours) post-dose |
Outcome Measure Data
| 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 |
|---|---|---|---|---|
| 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. |
| Measure Participants | 13 | 4 | 25 | 3 |
| Day 1 |
10116.7
(6683.97)
|
5817.5
(2966.26)
|
8005.9
(3251.32)
|
13096.7
(7453.39)
|
| Day 7 |
21812.5
(13090.21)
|
12227.5
(3480.09)
|
17996.0
(11555.15)
|
33800.0
(16263.46)
|
| Title | Cmax: Maximum Plasma Concentration for Vincristine |
|---|---|
| Description | |
| Time Frame | Cycles 1 and 2 on Day 1 prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 4 | 25 | 3 |
| Cycle 1, Day 1 |
132.2
(54.57)
|
105.4
(78.93)
|
158.4
(67.94)
|
| Cycle 2, Day 1 |
113.9
(53.86)
|
124.4
(157.70)
|
122.3
(36.42)
|
| Title | AUCt: Area Under the Concentration-time Time Curve Over the Dosing Interval From Time 0 to Time t for Vincristine |
|---|---|
| Description | |
| Time Frame | Cycles 1 and 2 on Day 1 prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 4 | 24 | 3 |
| Cycle 1, Day 1 |
69.8
(9.92)
|
69.1
(33.24)
|
104.1
(43.34)
|
| Cycle 2, Day 1 |
60.8
(2.26)
|
72.8
(30.40)
|
72.2
(32.60)
|
| Title | AUC∞: Area Under the Concentration-time Curve From Time 0 to Infinity for Vincristine |
|---|---|
| Description | |
| Time Frame | Cycles 1 and 2 on Day 1 prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 4 | 22 | 3 |
| Cycle 1, Day 1 |
77.9
(11.25)
|
84.8
(36.21)
|
116.8
(44.95)
|
| Cycle 2, Day 1 |
69.0
(4.45)
|
82.7
(35.39)
|
| Title | T1/2: Terminal Disposition Phase Half-life for Vincristine |
|---|---|
| Description | |
| Time Frame | Cycles 1 and 2 on Day prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 4 | 25 | 3 |
| Cycle 1, Day 1 |
20.2
(5.04)
|
20.0
(5.89)
|
25.6
(4.55)
|
| Cycle 2, Day 1 |
19.9
(0.92)
|
20.2
(4.66)
|
Adverse Events
| 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 | ||||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Safety Lead-in | Dose Escalation, Alisertib 30 mg | Dose Escalation, Alisertib 40 mg | Dose Escalation, Alisertib 50 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/13 (46.2%) | 1/4 (25%) | 12/25 (48%) | 3/3 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Febrile neutropenia | 0/13 (0%) | 0/4 (0%) | 3/25 (12%) | 3/3 (100%) | ||||
| Neutropenia | 0/13 (0%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Anaemia | 2/13 (15.4%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Thrombocytopenia | 0/13 (0%) | 0/4 (0%) | 0/25 (0%) | 1/3 (33.3%) | ||||
| Cardiac disorders | ||||||||
| Myocardial infarction | 0/13 (0%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Diarrhoea | 0/13 (0%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Stomatitis | 0/13 (0%) | 0/4 (0%) | 0/25 (0%) | 2/3 (66.7%) | ||||
| Upper gastrointestinal haemorrhage | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Ascites | 0/13 (0%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Abdominal pain | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| General disorders | ||||||||
| Pyrexia | 2/13 (15.4%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Asthenia | 0/13 (0%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Fatigue | 0/13 (0%) | 0/4 (0%) | 0/25 (0%) | 1/3 (33.3%) | ||||
| Infections and infestations | ||||||||
| Sepsis | 0/13 (0%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Septic shock | 0/13 (0%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Clostridium difficile colitis | 0/13 (0%) | 0/4 (0%) | 0/25 (0%) | 1/3 (33.3%) | ||||
| Enterobacter bacteraemia | 0/13 (0%) | 0/4 (0%) | 0/25 (0%) | 1/3 (33.3%) | ||||
| Herpes zoster | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Klebsiella bacteraemia | 0/13 (0%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Pneumonia | 0/13 (0%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Soft tissue infection | 0/13 (0%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Hypercalcaemia | 0/13 (0%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Hypokalaemia | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Myelodysplastic syndrome | 0/13 (0%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Spinal cord neoplasm | 0/13 (0%) | 1/4 (25%) | 0/25 (0%) | 0/3 (0%) | ||||
| Malignant pleural effusion | 0/13 (0%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Nervous system disorders | ||||||||
| Spinal cord compression | 0/13 (0%) | 1/4 (25%) | 0/25 (0%) | 0/3 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnoea | 2/13 (15.4%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Tachypnoea | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Pulmonary embolism | 1/13 (7.7%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Respiratory failure | 1/13 (7.7%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Pleural effusion | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Vascular disorders | ||||||||
| Hypotension | 0/13 (0%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Orthostatic hypotension | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Safety Lead-in | Dose Escalation, Alisertib 30 mg | Dose Escalation, Alisertib 40 mg | Dose Escalation, Alisertib 50 mg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/13 (100%) | 4/4 (100%) | 25/25 (100%) | 3/3 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 6/13 (46.2%) | 3/4 (75%) | 15/25 (60%) | 2/3 (66.7%) | ||||
| Leukopenia | 8/13 (61.5%) | 2/4 (50%) | 9/25 (36%) | 3/3 (100%) | ||||
| Neutropenia | 7/13 (53.8%) | 2/4 (50%) | 11/25 (44%) | 2/3 (66.7%) | ||||
| Thrombocytopenia | 7/13 (53.8%) | 1/4 (25%) | 8/25 (32%) | 3/3 (100%) | ||||
| Lymphopenia | 2/13 (15.4%) | 2/4 (50%) | 1/25 (4%) | 1/3 (33.3%) | ||||
| Pancytopenia | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Cardiac disorders | ||||||||
| Pericardial effusion | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Ear discomfort | 0/13 (0%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Deafness unilateral | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Vertigo | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Eye disorders | ||||||||
| Vision blurred | 1/13 (7.7%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Ocular icterus | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Diarrhoea | 4/13 (30.8%) | 0/4 (0%) | 16/25 (64%) | 0/3 (0%) | ||||
| Nausea | 1/13 (7.7%) | 1/4 (25%) | 14/25 (56%) | 1/3 (33.3%) | ||||
| Constipation | 2/13 (15.4%) | 1/4 (25%) | 9/25 (36%) | 1/3 (33.3%) | ||||
| Stomatitis | 2/13 (15.4%) | 0/4 (0%) | 6/25 (24%) | 1/3 (33.3%) | ||||
| Vomiting | 1/13 (7.7%) | 1/4 (25%) | 6/25 (24%) | 1/3 (33.3%) | ||||
| Abdominal pain | 3/13 (23.1%) | 0/4 (0%) | 4/25 (16%) | 0/3 (0%) | ||||
| Dyspepsia | 0/13 (0%) | 0/4 (0%) | 3/25 (12%) | 1/3 (33.3%) | ||||
| Abdominal distension | 0/13 (0%) | 0/4 (0%) | 3/25 (12%) | 0/3 (0%) | ||||
| Dysphagia | 1/13 (7.7%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Gastrooesophageal reflux disease | 0/13 (0%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Haemorrhoids | 2/13 (15.4%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Oral pain | 1/13 (7.7%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Proctalgia | 0/13 (0%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Aphthous ulcer | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Hypoaesthesia oral | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Oral discomfort | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Paraesthesia oral | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Tongue ulceration | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Toothache | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| General disorders | ||||||||
| Fatigue | 4/13 (30.8%) | 2/4 (50%) | 11/25 (44%) | 2/3 (66.7%) | ||||
| Chills | 2/13 (15.4%) | 0/4 (0%) | 3/25 (12%) | 0/3 (0%) | ||||
| Oedema peripheral | 1/13 (7.7%) | 1/4 (25%) | 3/25 (12%) | 0/3 (0%) | ||||
| Asthenia | 1/13 (7.7%) | 1/4 (25%) | 1/25 (4%) | 0/3 (0%) | ||||
| Pyrexia | 1/13 (7.7%) | 0/4 (0%) | 1/25 (4%) | 1/3 (33.3%) | ||||
| Early satiety | 0/13 (0%) | 0/4 (0%) | 1/25 (4%) | 1/3 (33.3%) | ||||
| Peripheral swelling | 0/13 (0%) | 0/4 (0%) | 1/25 (4%) | 1/3 (33.3%) | ||||
| Adverse drug reaction | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Infusion site erythema | 0/13 (0%) | 0/4 (0%) | 0/25 (0%) | 1/3 (33.3%) | ||||
| Injection site pain | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Pain | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Temperature regulation disorder | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Infections and infestations | ||||||||
| Urinary tract infection | 1/13 (7.7%) | 0/4 (0%) | 6/25 (24%) | 2/3 (66.7%) | ||||
| Upper respiratory tract infection | 1/13 (7.7%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Bronchitis | 0/13 (0%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Nasopharyngitis | 1/13 (7.7%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Sinusitis | 1/13 (7.7%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Tooth infection | 1/13 (7.7%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Diverticulitis | 0/13 (0%) | 1/4 (25%) | 0/25 (0%) | 0/3 (0%) | ||||
| Otitis media | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Pharyngitis | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Pharyngitis bacterial | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Infusion related reaction | 0/13 (0%) | 0/4 (0%) | 3/25 (12%) | 1/3 (33.3%) | ||||
| Fall | 1/13 (7.7%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Head Injury | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Investigations | ||||||||
| Neutrophil count decreased | 1/13 (7.7%) | 0/4 (0%) | 3/25 (12%) | 1/3 (33.3%) | ||||
| Aspartate aminotransferase increased | 0/13 (0%) | 0/4 (0%) | 1/25 (4%) | 2/3 (66.7%) | ||||
| Platelet count decreased | 1/13 (7.7%) | 0/4 (0%) | 1/25 (4%) | 1/3 (33.3%) | ||||
| Weight decreased | 1/13 (7.7%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Alanine aminotransferase increased | 0/13 (0%) | 0/4 (0%) | 0/25 (0%) | 2/3 (66.7%) | ||||
| Electrocardiogram QT prolonged | 2/13 (15.4%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Blood bilirubin increased | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Lymphocyte count decreased | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| White blood cell count decreased | 0/13 (0%) | 0/4 (0%) | 0/25 (0%) | 1/3 (33.3%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 3/13 (23.1%) | 1/4 (25%) | 7/25 (28%) | 1/3 (33.3%) | ||||
| Hypokalaemia | 4/13 (30.8%) | 0/4 (0%) | 6/25 (24%) | 2/3 (66.7%) | ||||
| Hypomagnesaemia | 2/13 (15.4%) | 0/4 (0%) | 5/25 (20%) | 1/3 (33.3%) | ||||
| Hyperglycaemia | 1/13 (7.7%) | 1/4 (25%) | 2/25 (8%) | 1/3 (33.3%) | ||||
| Hypoalbuminaemia | 3/13 (23.1%) | 0/4 (0%) | 0/25 (0%) | 2/3 (66.7%) | ||||
| Dehydration | 0/13 (0%) | 0/4 (0%) | 4/25 (16%) | 0/3 (0%) | ||||
| Hypocalcaemia | 2/13 (15.4%) | 0/4 (0%) | 1/25 (4%) | 1/3 (33.3%) | ||||
| Hyponatraemia | 2/13 (15.4%) | 0/4 (0%) | 0/25 (0%) | 1/3 (33.3%) | ||||
| Hypophosphataemia | 1/13 (7.7%) | 0/4 (0%) | 1/25 (4%) | 1/3 (33.3%) | ||||
| Hypercalcaemia | 1/13 (7.7%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Hypermagnesaemia | 0/13 (0%) | 0/4 (0%) | 0/25 (0%) | 1/3 (33.3%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 0/13 (0%) | 1/4 (25%) | 3/25 (12%) | 1/3 (33.3%) | ||||
| Myalgia | 2/13 (15.4%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Arthralgia | 0/13 (0%) | 0/4 (0%) | 3/25 (12%) | 0/3 (0%) | ||||
| Musculoskeletal pain | 1/13 (7.7%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Bone pain | 0/13 (0%) | 0/4 (0%) | 1/25 (4%) | 1/3 (33.3%) | ||||
| Flank pain | 2/13 (15.4%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Muscle spasms | 0/13 (0%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Musculoskeletal chest pain | 0/13 (0%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Neck pain | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Pain in jaw | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 2/13 (15.4%) | 1/4 (25%) | 6/25 (24%) | 1/3 (33.3%) | ||||
| Headache | 1/13 (7.7%) | 1/4 (25%) | 5/25 (20%) | 0/3 (0%) | ||||
| Neuropathy peripheral | 0/13 (0%) | 2/4 (50%) | 3/25 (12%) | 0/3 (0%) | ||||
| Peripheral sensory neuropathy | 0/13 (0%) | 0/4 (0%) | 4/25 (16%) | 1/3 (33.3%) | ||||
| Somnolence | 5/13 (38.5%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Paraesthesia | 0/13 (0%) | 1/4 (25%) | 2/25 (8%) | 0/3 (0%) | ||||
| Aphasia | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Neuralgia | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Tongue paralysis | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Psychiatric disorders | ||||||||
| Insomnia | 1/13 (7.7%) | 0/4 (0%) | 4/25 (16%) | 0/3 (0%) | ||||
| Anxiety | 0/13 (0%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Depression | 1/13 (7.7%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Confusional state | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Mental status changes | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Personality change | 0/13 (0%) | 1/4 (25%) | 0/25 (0%) | 0/3 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Hydronephrosis | 1/13 (7.7%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Urinary incontinence | 1/13 (7.7%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Dysuria | 0/13 (0%) | 1/4 (25%) | 0/25 (0%) | 0/3 (0%) | ||||
| Hydroureter | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Nocturia | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Prostatitis | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Vaginal ulceration | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnoea | 1/13 (7.7%) | 0/4 (0%) | 7/25 (28%) | 0/3 (0%) | ||||
| Cough | 2/13 (15.4%) | 0/4 (0%) | 3/25 (12%) | 0/3 (0%) | ||||
| Oropharyngeal pain | 2/13 (15.4%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Dysphonia | 1/13 (7.7%) | 0/4 (0%) | 1/25 (4%) | 1/3 (33.3%) | ||||
| Epistaxis | 0/13 (0%) | 1/4 (25%) | 2/25 (8%) | 0/3 (0%) | ||||
| Nasal congestion | 0/13 (0%) | 0/4 (0%) | 3/25 (12%) | 0/3 (0%) | ||||
| Nasal ulcer | 0/13 (0%) | 0/4 (0%) | 0/25 (0%) | 1/3 (33.3%) | ||||
| Pharyngeal inflammation | 0/13 (0%) | 0/4 (0%) | 0/25 (0%) | 1/3 (33.3%) | ||||
| Pleural effusion | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Sneezing | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 3/13 (23.1%) | 1/4 (25%) | 5/25 (20%) | 0/3 (0%) | ||||
| Pruritus | 2/13 (15.4%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Rash maculo-papular | 1/13 (7.7%) | 0/4 (0%) | 3/25 (12%) | 0/3 (0%) | ||||
| Rash macular | 1/13 (7.7%) | 1/4 (25%) | 0/25 (0%) | 1/3 (33.3%) | ||||
| Palmar-plantar erythrodysaesthesia syndrome | 0/13 (0%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Rash | 2/13 (15.4%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
| Rash erythematous | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 1/3 (33.3%) | ||||
| Vascular disorders | ||||||||
| Hypotension | 0/13 (0%) | 0/4 (0%) | 2/25 (8%) | 1/3 (33.3%) | ||||
| Orthostatic hypotension | 1/13 (7.7%) | 2/4 (50%) | 0/25 (0%) | 0/3 (0%) | ||||
| Deep vein thrombosis | 0/13 (0%) | 0/4 (0%) | 2/25 (8%) | 0/3 (0%) | ||||
| Thrombophlebitis superficial | 1/13 (7.7%) | 0/4 (0%) | 1/25 (4%) | 0/3 (0%) | ||||
| Hypertension | 1/13 (7.7%) | 0/4 (0%) | 0/25 (0%) | 0/3 (0%) | ||||
Limitations/Caveats
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.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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 |
| trialdisclosures@takeda.com |
Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01397825
Other Study ID Numbers:
- C14011
- 2011-000609-32
- U1111-1181-0333
- 12/NE/0268
First Posted:
Jul 20, 2011
Last Update Posted:
Mar 27, 2018
Last Verified:
Feb 1, 2018