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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-000609-32 | EudraCT Number | ||
| U1111-1181-0333 | Registry Identifier | WHO | |
| 12/NE/0268 | Registry Identifier | NRES |
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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.
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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Safety Lead-in | Experimental | 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. |
|
| Dose Escalation, Alisertib 30 mg | Experimental | 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. |
|
| Dose Escalation, Alisertib 40 mg | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alisertib (MLN8237) | Drug | Alisertib (MLN8237) enteric coated tablet (ECT). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Clinically Significant Vital Signs Findings (Treatment Related and Unrelated) [Phase 1] | Vital sign parameters: blood pressure, heart rate and temperature determined by the investigator to be clinically significant were reported as adverse events. | First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years) |
| Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs) [Phase 1] | Abnormal ECGs findings determined by the investigator to be clinically significant were reported as adverse events. | First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years) |
| Number of Participants With Clinically Significant Changes in Multigated Acquisition (MUGA)/ Echocardiogram (ECHO) [Phase 1] | Abnormal changes in MUGA and ECHO findings determined by the investigator to be clinically significant were reported as adverse events. | First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years) |
| Number of Participants With Clinically Significant Changes in Physical Examination Findings [Phase 1] | Abnormal Physical Examination findings determined by the investigator to be clinically significant were reported as Adverse Events. | First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years) |
| Number of Participants With Clinically Significant Laboratory Tests Reported as Adverse Events [Phase 1] | Abnormal treatment-emergent Chemistry and Hematology Laboratory values determined by the investigator to be clinically significant were reported as adverse events. | First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years) |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate as Assessed by the Investigator [Phase 1] | 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. |
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Inclusion Criteria:
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Millennium Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tucson | Arizona | United States | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30082475 | Derived | Kelly KR, Friedberg JW, Park SI, McDonagh K, Hayslip J, Persky D, Ruan J, Puvvada S, Rosen P, Iyer SP, Stefanovic A, Bernstein SH, Weitman S, Karnad A, Monohan G, VanderWalde A, Mena R, Schmelz M, Spier C, Groshen S, Venkatakrishnan K, Zhou X, Sheldon-Waniga E, Leonard EJ, Mahadevan D. Phase I Study of the Investigational Aurora A Kinase Inhibitor Alisertib plus Rituximab or Rituximab/Vincristine in Relapsed/Refractory Aggressive B-cell Lymphoma. Clin Cancer Res. 2018 Dec 15;24(24):6150-6159. doi: 10.1158/1078-0432.CCR-18-0286. Epub 2018 Aug 6. |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Dose Escalation, Alisertib 50 mg | Experimental | 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. |
|
| Phase 2: Alisertib | Experimental | 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. |
|
| Rituximab | Drug | Rituximab IV infusion. |
|
| Vincristine | Drug | Vincristine IV Infusion. |
|
| Number of Participants With Treatment-Emergent Adverse Events [Phase 1] | 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. | First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years) |
| Overall Response Rate [Phase 2] | 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. | 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 |
| First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years) |
| Complete Response Rate [Phase 2] | 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 study until disease progression, approximately 2 years |
| Duration of Response (DOR) [Phase 2] | 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). | Duration of study until disease progression, approximately 2 years |
| Progression Free Survival (PFS) [Phase 2] | PFS was defined as the time from the date of first study drug administration to the date of first documentation of PD or death. | Duration of study until disease progression, approximately 2 years |
| Number of Participants With Treatment-Emergent Adverse Events [Phase 2] | 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. | From screening period to 30 days after last dose of study drug, approximately 2 years |
| Number of Participants With Clinically Significant Vital Signs Findings [Phase 2] | Vital sign parameters: blood pressure, heart rate and temperature determined by the investigator to be clinically significant were reported as adverse events. | From screening period to 30 days after last dose of study drug, approximately 2 years |
| 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 |
| Beverly Hills |
| California |
| United States |
| Burbank | California | United States |
| Miami | Florida | United States |
| Lexington | Kentucky | United States |
| Worcester | Massachusetts | United States |
| New York | New York | United States |
| Rochester | New York | United States |
| Chapel Hill | North Carolina | United States |
| Philadelphia | Pennsylvania | United States |
| Germantown | Tennessee | United States |
| Memphis | Tennessee | United States |
| Houston | Texas | United States |
| San Antonio | Texas | United States |
| Burlington | Vermont | United States |
| Orbassano | Torino | Italy |
| Genova | Italy |
| Palermo | Italy |
| Roma | Italy |
| Madrid | Spain |
| Seville | Spain |
| Aberdeen | Grampian Region | United Kingdom |
| London | Greater London | United Kingdom |
| Southampton | Hampshire | United Kingdom |
| Birmingham | West Midlands | United Kingdom |
| FG001 | 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, 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. |
| FG002 | 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 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. |
| FG003 | 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 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. |
| FG004 | 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. |
| COMPLETED |
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| NOT COMPLETED |
|
|
Safety Population was defined as all participants who receive any amount of alisertib.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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, 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. |
| BG002 | 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 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. |
| BG003 | 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 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. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Region of Enrollment | Number | participants |
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| Height | Mean | Standard Deviation | cm |
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| Weight | Mean | Standard Deviation | kg |
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| Body Surface Area | Body surface area (m^²)=square root [height (cm)×weight (kg)/3600]. | Mean | Standard Deviation | m^2 |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Clinically Significant Vital Signs Findings (Treatment Related and Unrelated) [Phase 1] | Vital sign parameters: blood pressure, heart rate and temperature determined by the investigator to be clinically significant were reported as adverse events. | Safety Population was defined as all participants who receive any amount of alisertib. | Posted | Number | participants | First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years) |
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| Primary | Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs) [Phase 1] | Abnormal ECGs findings determined by the investigator to be clinically significant were reported as adverse events. | Safety Population was defined as all participants who receive any amount of alisertib. | Posted | Number | participants | First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years) |
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| Primary | Number of Participants With Clinically Significant Changes in Multigated Acquisition (MUGA)/ Echocardiogram (ECHO) [Phase 1] | Abnormal changes in MUGA and ECHO findings determined by the investigator to be clinically significant were reported as adverse events. | Safety Population was defined as all participants who receive any amount of alisertib. | Posted | Number | participants | First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years) |
| |||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Clinically Significant Changes in Physical Examination Findings [Phase 1] | Abnormal Physical Examination findings determined by the investigator to be clinically significant were reported as Adverse Events. | Safety Population was defined as all participants who receive any amount of alisertib. | Posted | Number | participants | First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years) |
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| Primary | Number of Participants With Clinically Significant Laboratory Tests Reported as Adverse Events [Phase 1] | Abnormal treatment-emergent Chemistry and Hematology Laboratory values determined by the investigator to be clinically significant were reported as adverse events. | Safety Population was defined as all participants who receive any amount of alisertib. | Posted | Number | participants | First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years) |
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| Primary | Number of Participants With Treatment-Emergent Adverse Events [Phase 1] | 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. | Safety Population was defined as all participants who receive any amount of alisertib. | Posted | Number | participants | First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years) |
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| Primary | Overall Response Rate [Phase 2] | 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. | The Phase 2 portion of the study was cancelled by the sponsor. | Posted | 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 |
|
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| Secondary | Overall Response Rate as Assessed by the Investigator [Phase 1] | 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years) |
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| Secondary | Complete Response Rate [Phase 2] | 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. | Phase 2 portion of the study was cancelled by the sponsor. | Posted | Duration of study until disease progression, approximately 2 years |
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| Secondary | Duration of Response (DOR) [Phase 2] | 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). | Phase 2 portion of the study was cancelled by the sponsor. | Posted | Duration of study until disease progression, approximately 2 years |
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| Secondary | Progression Free Survival (PFS) [Phase 2] | PFS was defined as the time from the date of first study drug administration to the date of first documentation of PD or death. | The Phase 2 portion of the study was cancelled by the sponsor. | Posted | Duration of study until disease progression, approximately 2 years |
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| Secondary | Number of Participants With Treatment-Emergent Adverse Events [Phase 2] | 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. | Phase 2 portion of the study was cancelled by the sponsor. | Posted | From screening period to 30 days after last dose of study drug, approximately 2 years |
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| Secondary | Number of Participants With Clinically Significant Vital Signs Findings [Phase 2] | Vital sign parameters: blood pressure, heart rate and temperature determined by the investigator to be clinically significant were reported as adverse events. | Phase 2 portion of the study was cancelled by the sponsor. | Posted | From screening period to 30 days after last dose of study drug, approximately 2 years |
|
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| Secondary | Number of Participants With Clinically Significant Changes in Electrocardiograms (ECGs) [Phase 2] | Phase 2 portion of the study was cancelled by the sponsor. | Posted | From screening period to 30 days after last dose of study drug, approximately 2 years |
|
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| Secondary | Number of Participants With Clinically Significant Changes in Multigated Acquisition (MUGA)/ Echocardiogram (ECHO) [Phase 2] | Phase 2 portion of the study was cancelled by the sponsor. | Posted | From screening period to 30 days after last dose of study drug, approximately 2 years |
|
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| Secondary | Number of Participants With Clinically Significant Laboratory Tests Reported as Adverse Events [Phase 2] | Phase 2 portion of the study was cancelled by the sponsor. | Posted | From screening period to 30 days after last dose of study drug, approximately 2 years |
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| Secondary | Cmax: Maximum Plasma Concentration for Alisertib | 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. | Posted | Mean | Standard Deviation | nanoMolar (nM) | Cycle 1 Days 1 and 7 prior to morning alisertib dose and multiple time-points (up to 12 hours) post-dose |
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| Secondary | Tmax: Time to First Occurrence of Cmax fo Alisertib | 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. | Posted | Median | Full Range | hours (hr) | Cycle 1 Days 1 and 7 prior to morning alisertib dose and multiple time-points (up to 12 hours) post-dose |
| |||||||||||||||||||||||||||||||||||||
| Secondary | AUCt: Area Under the Concentration Time Curve Over the Dosing Interval From Time 0 to Time t for Alisertib | 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. | Posted | Mean | Standard Deviation | nanomoles/liter*hour (nmol/L*hr) | Cycle 1 Days 1 and 7 prior to morning alisertib dose and multiple time-points (up to 12 hours) post-dose |
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| Secondary | Cmax: Maximum Plasma Concentration for Vincristine | 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. | Posted | Mean | Standard Deviation | ng/mL | Cycles 1 and 2 on Day 1 prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose |
| |||||||||||||||||||||||||||||||||||||
| Secondary | AUCt: Area Under the Concentration-time Time Curve Over the Dosing Interval From Time 0 to Time t for Vincristine | 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. | Posted | Mean | Standard Deviation | ng/mL*hr | Cycles 1 and 2 on Day 1 prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose |
| |||||||||||||||||||||||||||||||||||||
| Secondary | AUC∞: Area Under the Concentration-time Curve From Time 0 to Infinity for Vincristine | 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. | Posted | Mean | Standard Deviation | ng/mL*hr | Cycles 1 and 2 on Day 1 prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose |
| |||||||||||||||||||||||||||||||||||||
| Secondary | T1/2: Terminal Disposition Phase Half-life for Vincristine | 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. | Posted | Mean | Standard Deviation | nanogram/milliliter (ng/mL) | Cycles 1 and 2 on Day prior to injection of vincristine and multiple time-points (up to 72 hours) post-dose |
|
First dose of alisertib through 30 days after the last dose of alisertib (Up to 5.2 Years)
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 6 | 13 | 13 | 13 | ||
| EG001 | 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, 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. | 1 | 4 | 4 | 4 | ||
| EG002 | 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 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. | 12 | 25 | 25 | 25 | ||
| EG003 | 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 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. | 3 | 3 | 3 | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA 19.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with alisertib 40 mg BID and is not related. |
|
| Clostridium difficile colitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Enterobacter bacteraemia | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Klebsiella bacteraemia | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Soft tissue infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment | Two treatment-emergent deaths occurred during treatment with alisertib 50 mg BID and alisertib 40 mg BID and are not related. |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment | One treatment-emergent death occurred during treatment with 50 mg BID and is not related. |
|
| Myelodysplastic syndrome | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.0 | Systematic Assessment |
| |
| Spinal cord neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.0 | Systematic Assessment |
| |
| Malignant pleural effusion | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 19.0 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Spinal cord compression | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Proctalgia | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Aphthous ulcer | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Oral discomfort | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Paraesthesia oral | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Tongue ulceration | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Early satiety | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Adverse drug reaction | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Infusion site erythema | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Temperature regulation disorder | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypermagnesaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Neuralgia | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Tongue paralysis | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Nasal ulcer | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pharyngeal inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Pharyngitis bacterial | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 19.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Personality change | Psychiatric disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Thrombophlebitis superficial | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Head Injury | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Urinary incontinence | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Hydroureter | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Nocturia | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Ear discomfort | Ear and labyrinth disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Deafness unilateral | Ear and labyrinth disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Ocular icterus | Eye disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Prostatitis | Reproductive system and breast disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Vaginal ulceration | Reproductive system and breast disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pericardial effusion | Cardiac disorders | MedDRA 19.0 | Systematic Assessment |
|
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.
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
| ID | Term |
|---|---|
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| D020522 | Lymphoma, Mantle-Cell |
| D002051 | Burkitt Lymphoma |
| ID | Term |
|---|---|
| D016393 | Lymphoma, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D020031 | Epstein-Barr Virus Infections |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D014412 | Tumor Virus Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| C550258 | MLN 8237 |
| D000069283 | Rituximab |
| D014750 | Vincristine |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Black or African American |
|
| Asian |
|
| Other |
|
| Not Reported |
|
| Orthostatic hypotension |
|
| Hypertension |
|
| Pyrexia |
|
| OG002 | 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 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. |
| OG003 | 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 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. |
|
|
| OG002 | 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 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. |
| OG003 | 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 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. |
|
|
| OG002 | 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 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. |
| OG003 | 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 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. |
|
|
| OG002 | 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 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. |
| OG003 | 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 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. |
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| OG002 | 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 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. |
| OG003 | 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 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. |
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| OG002 | 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 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. |
| OG003 | 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 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. |
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| OG002 | 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 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. |
| OG003 | 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 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. |
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| OG002 |
| 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 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. |
| OG003 | 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 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. |
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| OG002 | 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 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. |
| OG003 | 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 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. |
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| OG002 | 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 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. |
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| OG002 | 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 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. |
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| OG002 | 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 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. |
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| OG002 | 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 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. |
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