Burkitt's Lymphoma, Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, T-cell Lymphoma, Excluding Primary Cutaneous T-cell Lymphoma, Transformed Follicular Lymphoma With ≥ 50% Diffuse Large Cell Component
Conditions
Keywords
MLN8237, Alisertib, Drug therapy
Brief summary
The purpose of this study is to evaluate the anti-tumor activity of alisertib (MLN8237) in participants with relapsed or refractory non-hodgkin's lymphoma.
Detailed description
The drug being tested in this study is called alisertib (MLN8237). Alisertib is being tested to treat people who have relapsed or refractory non-Hodgkin's lymphoma (NHL). The study looked at anti-tumor activity in participants who received alisertib. The study enrolled 48 patients. Participants were categorized as per disease subtypes into five subtypes: Large B-Cell lymphoma, mantle cell lymphoma, transformed follicular lymphoma, Burkitts lymphoma and aggressive T-Cell lymphoma (Note: There were no participants enrolled with Precursor B-lymphoblastic Leukemia/Lymphoma). Participants received: • Alisertib 50 mg BID on Days 1 to 7 All participants took alisertib capsules approximately every 12 hours each day for 7 days followed by a 14-day rest period in a 21-days cycle. MLN8237 was supplied in capsules of 5 or 25 mg strength. This multi-center trial was conducted in United States. The overall time to participate in this study was until there is evidence of disease progression or unacceptable treatment-related toxicity. If the participant would derive benefit from continued alisertib treatment beyond 24 months, the Sponsor was consulted for approval of further treatment. Participants made multiple visits to the clinic, with imaging assessments every 12 weeks. Participants discontinuing treatment prior to disease progression continue with clinic visits, chemistry and hematology lab testing, and tumor assessments every 12 weeks up to 12 months after last dose of study drug for follow-up assessments.
Interventions
DRUGAlisertib
Alisertib capsules
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Each participant must meet all of the following inclusion criteria to be enrolled in the study: 1. Participant must have histological or cytological diagnosis of a hematological malignancy of the following types that has relapsed or was refractory to prior therapy: * Diffuse large B-cell lymphoma * Mantle cell lymphoma * Burkitt's lymphoma * Precursor B-lymphoblastic leukemia/lymphoma * T-cell lymphoma, excluding primary cutaneous T-cell lymphoma * Transformed follicular lymphoma with ≥ 50% diffuse large cell component. 2. Male or female participants 18 years or older. 3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. 4. Measurable disease.
Exclusion criteria
include the following: 1. Pregnant or lactating females. 2. Known human immunodeficiency virus (HIV) positive or AIDS-related illness. 3. Any serious medical or psychiatric illness that could interfere with the completion of treatment. 4. Total bilirubin ≥ 1.5 × the upper limit of normal (ULN). 5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 2.5 × the ULN. AST, ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to their underlying hematological disorder. 6. Absolute neutrophil count (ANC) \< 1,250/mm\^3. 7. Platelet count \< 75,000/mm\^3. 8. Calculated creatinine clearance \< 30 mL/minute. 9. Autologous stem cell transplant less than 6 months prior to enrollment. 10. Participants who have undergone allogeneic stem cell or organ transplantation. 11. Systemic antineoplastic therapy including glucocorticoids (\> 15 mg prednisone/day or equivalent), or treatment with an investigational agent within 14 days preceding the first dose of study drug treatment. 12. Participants who have received treatment with nitrosoureas, mitomycin C, rituximab, alemtuzumab, or other unconjugated antibody treatment, within 12 weeks prior to first dose. 13. Participants who have received treatment with radioimmunoconjugates or within 12 weeks prior to first dose. 14. Participants who have received radiotherapy within 21 days prior to first dose. 15. Myocardial infarction within 6 months of enrollment or current history of New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia. 16. Major surgery within 14 days prior to the first dose. 17. Infection requiring systemic antibiotic therapy within 14 days prior to the first dose or other serious infection. 18. Clinically uncontrolled central nervous system (CNS) involvement. 19. Inability to swallow capsules. 20. History of uncontrolled sleep apnoea syndrome and other conditions that could result in excessive daytime sleepiness (eg, Chronic obstructive pulmonary disease - COPD).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response Rate Based on Investigator's Assessment (Applying the IWG 2007 Response Criteria) | Baseline and every 2 cycles up to Month 12 (approximately 16 cycles), from Cycle 16 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months from last dose (Up to 4 years) | Best overall response rate is 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 (as specified in the Cheson 2007, IWG response criteria). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Baseline and every 2 cycles up to Month 12, from Cycle 16 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Up to 4 years) | PFS is defined as the time in days from the date of first study drug administration to the date of first documentation of progressive disease (PD) or death. |
| Duration of Response (DOR) | Baseline and every 2 cycles up to Month 12, from Cycle 16 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Up to 4 years) | DOR is defined as the time from the date of first documentation of a CR, or partial response (PR) to the date of first documentation of PD according to IWG criteria. CR definition includes the complete disappearance of all evidence of disease, the definition of PR includes at least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses, and PD is defined as any new lesion or increase by \>50% of previously involved sites from nadir, as described in the IWG response criteria (Cheson 2007). |
| Time to Progression (TTP) | Baseline and every 2 cycles up to Month 12, from Cycle 16 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Up to 4 years) | Time to progression (TTP) is defined as the time in days from the date of first study drug administration to the date of first documentation of Progressive Disease (PD) according to IWG criteria (Cheson 2007). PD is defined as any new lesion or increase by \>50% of previously involved sites from nadir. |
| Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | First dose of study drug to 30 days after last dose (Up to 25 months) | Vital signs (blood pressure, heart rate, and oral temperature) measurements were obtained throughout the study. 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 Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | First dose of study drug to 30 days after last dose (Up to 25 months) | Abnormal laboratory values for chemistry or hematology tests that were assessed by the investigator using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE V4). 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 Treatment-Emergent Adverse Events | First dose of study drug to 30 days after last dose (Up to 25 months) | 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 and includes all-causality (ie, treatment-related and not treatment-related as assessed by the investigator). |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 12 investigative sites in the United States from 10 February 2009 to last participant off study 13 February 2013, with a data cut-off on 04 January 2011 to report the primary endpoint.
Pre-assignment details
Participants with a diagnosis of Aggressive Non-Hodgkin's Lymphoma received 50 mg alisertib twice daily for 7 days in 21 day cycles. Results are categorized as disease sub-types: Diffuse Large B-cell lymphoma (DLBL), Mantle Cell lymphoma (MCL), Transformed Follicular lymphoma (TFL), Burkitts lymphoma (BL) and Aggressive T-Cell lymphoma (ATL).
Participants by arm
| Arm | Count |
|---|---|
| Alisertib 50 mg BID Starting Dose (DLBL) Participants with diffuse large B-Cell lymphoma (DLBL) received alisertib 50 mg, capsules, orally, twice daily (BID) for 7 days, followed by 14-day rest period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 24 months). | 22 |
| Alisertib 50 mg BID Starting Dose (MCL) Participants with mantle cell lymphoma (MCL) received alisertib 50 mg, capsules, orally, BID for 7 days, followed by 14-day rest period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 24 months). | 13 |
| Alisertib 50 mg BID Starting Dose (TFL) Participants with transformed follicular lymphoma (TFL) received alisertib 50 mg, capsules, orally, BID for 7 days, followed by 14-day rest period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 24 months). | 5 |
| Alisertib 50 mg BID Starting Dose (BL) Participants with Burkitts lymphoma (BL) received alisertib 50 mg, capsules, orally, BID for 7 days, followed by 14-day rest period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 24 months). | 1 |
| Alisertib 50 mg BID Starting Dose (ATL) Participants with aggressive T-Cell lymphoma (ATL) received alisertib 50 mg, capsules, orally, BID for 7 days, followed by 14-day rest period in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 24 months). | 7 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 3 | 1 | 1 | 2 |
| Overall Study | Reason Not Specified | 0 | 3 | 2 | 0 | 3 |
| Overall Study | Withdrawal by Patient | 2 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Alisertib 50 mg BID Starting Dose (DLBL) | Alisertib 50 mg BID Starting Dose (MCL) | Alisertib 50 mg BID Starting Dose (TFL) | Alisertib 50 mg BID Starting Dose (BL) | Alisertib 50 mg BID Starting Dose (ATL) | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 66.8 years STANDARD_DEVIATION 11.11 | 67.2 years STANDARD_DEVIATION 6.71 | 65.2 years STANDARD_DEVIATION 9.96 | 76.0 years | 54.4 years STANDARD_DEVIATION 16.9 | 65.1 years STANDARD_DEVIATION 11.56 |
| Race/Ethnicity, Customized Hispanic or Latino | 1 participants | 0 participants | 1 participants | 0 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 21 participants | 13 participants | 4 participants | 1 participants | 6 participants | 45 participants |
| Race/Ethnicity, Customized Other | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 21 participants | 13 participants | 5 participants | 1 participants | 7 participants | 47 participants |
| Sex: Female, Male Female | 9 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 13 Participants |
| Sex: Female, Male Male | 13 Participants | 12 Participants | 2 Participants | 1 Participants | 7 Participants | 35 Participants |
| Weight | 88.85 kg STANDARD_DEVIATION 27.022 | 96.18 kg STANDARD_DEVIATION 25.139 | 89.06 kg STANDARD_DEVIATION 29.724 | 72.58 kg | 84.45 kg STANDARD_DEVIATION 14.494 | 89.88 kg STANDARD_DEVIATION 24.737 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 22 / 22 | 13 / 13 | 5 / 5 | 1 / 1 | 7 / 7 |
| serious Total, serious adverse events | 16 / 22 | 4 / 13 | 5 / 5 | 0 / 1 | 4 / 7 |
Outcome results
Primary
Best Overall Response Rate Based on Investigator's Assessment (Applying the IWG 2007 Response Criteria)
Best overall response rate is 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 (as specified in the Cheson 2007, IWG response criteria).
Time frame: Baseline and every 2 cycles up to Month 12 (approximately 16 cycles), from Cycle 16 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months from last dose (Up to 4 years)
Population: Safety population was defined as all participants who received any amount of alisertib. Efficacy analysis for the response-evaluable population is a subset of the safety population, with participants having a minimum of baseline imaging and one on-study imaging.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alisertib 50 mg BID Starting Dose (DLBL) | Best Overall Response Rate Based on Investigator's Assessment (Applying the IWG 2007 Response Criteria) | 25 percentage of participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Best Overall Response Rate Based on Investigator's Assessment (Applying the IWG 2007 Response Criteria) | 23 percentage of participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Best Overall Response Rate Based on Investigator's Assessment (Applying the IWG 2007 Response Criteria) | 40 percentage of participants |
| Alisertib 50 mg BID Starting Dose (BL) | Best Overall Response Rate Based on Investigator's Assessment (Applying the IWG 2007 Response Criteria) | 100 percentage of participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Best Overall Response Rate Based on Investigator's Assessment (Applying the IWG 2007 Response Criteria) | 50 percentage of participants |
Secondary
Duration of Response (DOR)
DOR is defined as the time from the date of first documentation of a CR, or partial response (PR) to the date of first documentation of PD according to IWG criteria. CR definition includes the complete disappearance of all evidence of disease, the definition of PR includes at least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses, and PD is defined as any new lesion or increase by \>50% of previously involved sites from nadir, as described in the IWG response criteria (Cheson 2007).
Time frame: Baseline and every 2 cycles up to Month 12, from Cycle 16 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Up to 4 years)
Population: Response-evaluable population is subset of safety population, defined as all participants who received any amount of alisertib, having minimum of baseline imaging and one on-study imaging. All responders were evaluated in this outcome measure. Participants who had not progressed, DOR was censored at last response assessment that was SD or better.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alisertib 50 mg BID Starting Dose (DLBL) | Duration of Response (DOR) | 454.0 days |
| Alisertib 50 mg BID Starting Dose (MCL) | Duration of Response (DOR) | 646.0 days |
| Alisertib 50 mg BID Starting Dose (TFL) | Duration of Response (DOR) | NA days |
| Alisertib 50 mg BID Starting Dose (BL) | Duration of Response (DOR) | NA days |
| Alisertib 50 mg BID Starting Dose (ATL) | Duration of Response (DOR) | 596.0 days |
Secondary
Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events
Abnormal laboratory values for chemistry or hematology tests that were assessed by the investigator using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE V4). 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 study drug to 30 days after last dose (Up to 25 months)
Population: Safety population was defined as all participants who received any amount of alisertib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood creatinine increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypercalcaemia | 0 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood potassium decreased | 1 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypophosphataemia | 0 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Neutropenia | 13 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Lymphopenia | 1 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood urea increased | 1 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Aspartate aminotransferase increased | 6 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood alkaline phosphatase increased | 6 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Mean cell volume increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Thrombocytopenia | 11 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypokalaemia | 3 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Urine colour abnormal | 0 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypernatraemia | 0 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood lactate dehydrogenase increased | 3 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Alanine aminotransferase increased | 6 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypercalcaemia | 0 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Mean cell volume increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood alkaline phosphatase increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Alanine aminotransferase increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Thrombocytopenia | 5 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood potassium decreased | 0 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypernatraemia | 0 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood urea increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood creatinine increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood lactate dehydrogenase increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Lymphopenia | 0 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Neutropenia | 9 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypokalaemia | 0 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Aspartate aminotransferase increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Urine colour abnormal | 1 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypophosphataemia | 0 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypophosphataemia | 0 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Mean cell volume increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Aspartate aminotransferase increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Urine colour abnormal | 0 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Neutropenia | 3 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Thrombocytopenia | 3 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood alkaline phosphatase increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypokalaemia | 1 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood lactate dehydrogenase increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood creatinine increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood potassium decreased | 0 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Alanine aminotransferase increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Lymphopenia | 0 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood urea increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypercalcaemia | 0 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypernatraemia | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Aspartate aminotransferase increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood urea increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Urine colour abnormal | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood creatinine increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood lactate dehydrogenase increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Mean cell volume increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypercalcaemia | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Thrombocytopenia | 1 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypokalaemia | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood alkaline phosphatase increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypophosphataemia | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypernatraemia | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Neutropenia | 1 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Alanine aminotransferase increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Lymphopenia | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood potassium decreased | 0 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood urea increased | 0 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Thrombocytopenia | 5 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Alanine aminotransferase increased | 1 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Aspartate aminotransferase increased | 1 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood alkaline phosphatase increased | 1 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypokalaemia | 1 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood lactate dehydrogenase increased | 1 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood creatinine increased | 2 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Blood potassium decreased | 1 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Lymphopenia | 1 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypercalcaemia | 1 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypernatraemia | 1 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Hypophosphataemia | 1 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Mean cell volume increased | 1 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Urine colour abnormal | 0 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events | Neutropenia | 4 participants |
Secondary
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events
Vital signs (blood pressure, heart rate, and oral temperature) measurements were obtained throughout the study. 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 study drug to 30 days after last dose (Up to 25 months)
Population: Safety population was defined as all participants who received any amount of alisertib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Pyrexia | 7 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Cardiac flutter | 1 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Bradycardia | 1 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Weight decreased | 2 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Hypotension | 6 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Tachycardia | 1 participants |
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Hypertension | 1 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Hypertension | 0 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Tachycardia | 0 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Hypotension | 1 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Pyrexia | 0 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Bradycardia | 0 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Weight decreased | 1 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Cardiac flutter | 0 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Tachycardia | 0 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Pyrexia | 0 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Hypotension | 1 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Weight decreased | 0 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Hypertension | 0 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Bradycardia | 0 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Cardiac flutter | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Weight decreased | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Hypertension | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Hypotension | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Cardiac flutter | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Bradycardia | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Pyrexia | 0 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Tachycardia | 0 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Weight decreased | 1 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Cardiac flutter | 0 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Bradycardia | 0 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Hypertension | 0 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Hypotension | 1 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Pyrexia | 2 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events | Tachycardia | 2 participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events
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 and includes all-causality (ie, treatment-related and not treatment-related as assessed by the investigator).
Time frame: First dose of study drug to 30 days after last dose (Up to 25 months)
Population: Safety population was defined as all participants who received any amount of alisertib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alisertib 50 mg BID Starting Dose (DLBL) | Number of Participants With Treatment-Emergent Adverse Events | 22 participants |
| Alisertib 50 mg BID Starting Dose (MCL) | Number of Participants With Treatment-Emergent Adverse Events | 13 participants |
| Alisertib 50 mg BID Starting Dose (TFL) | Number of Participants With Treatment-Emergent Adverse Events | 5 participants |
| Alisertib 50 mg BID Starting Dose (BL) | Number of Participants With Treatment-Emergent Adverse Events | 1 participants |
| Alisertib 50 mg BID Starting Dose (ATL) | Number of Participants With Treatment-Emergent Adverse Events | 7 participants |
Secondary
Progression Free Survival (PFS)
PFS is defined as the time in days from the date of first study drug administration to the date of first documentation of progressive disease (PD) or death.
Time frame: Baseline and every 2 cycles up to Month 12, from Cycle 16 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Up to 4 years)
Population: Response-evaluable population is subset of safety population, defined as all participants who received any amount of alisertib, having minimum of baseline imaging and one on-study imaging. For a participant who had not progressed and had not died, PFS was censored at the last response assessment that was SD or better.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alisertib 50 mg BID Starting Dose (DLBL) | Progression Free Survival (PFS) | 84.0 days |
| Alisertib 50 mg BID Starting Dose (MCL) | Progression Free Survival (PFS) | 139.0 days |
| Alisertib 50 mg BID Starting Dose (TFL) | Progression Free Survival (PFS) | NA days |
| Alisertib 50 mg BID Starting Dose (BL) | Progression Free Survival (PFS) | NA days |
| Alisertib 50 mg BID Starting Dose (ATL) | Progression Free Survival (PFS) | 237.0 days |
Secondary
Time to Progression (TTP)
Time to progression (TTP) is defined as the time in days from the date of first study drug administration to the date of first documentation of Progressive Disease (PD) according to IWG criteria (Cheson 2007). PD is defined as any new lesion or increase by \>50% of previously involved sites from nadir.
Time frame: Baseline and every 2 cycles up to Month 12, from Cycle 16 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Up to 4 years)
Population: Response-evaluable population is subset of safety population, defined as all participants who received any amount of alisertib, having minimum of baseline imaging and one on-study imaging. Here number of participants analyzed were participants with PD. TTP was censored at the last response assessment that was SD or better.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alisertib 50 mg BID Starting Dose (DLBL) | Time to Progression (TTP) | 84.0 days |
| Alisertib 50 mg BID Starting Dose (MCL) | Time to Progression (TTP) | 139.0 days |
| Alisertib 50 mg BID Starting Dose (TFL) | Time to Progression (TTP) | NA days |
| Alisertib 50 mg BID Starting Dose (BL) | Time to Progression (TTP) | NA days |
| Alisertib 50 mg BID Starting Dose (ATL) | Time to Progression (TTP) | 237.0 days |