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Blood and Lymph Conditions

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All Conditions

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Lymphoma

Neoplasms by Histologic Type

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Immunoproliferative Disorders

Lymphosarcoma

Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.

Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.

Alisertib

Medical Director Clinical Science

The purpose of this study was to determine the safety profile, maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and to characterize the pharmacokinetic (PK) profile of alisertib twice daily (BID) dosing for 7 days in East Asian participants with advanced solid tumors or lymphomas. The secondary objective was to describe any antitumor activity that may have been observed with alisertib treatment.

The drug being tested in this study is called alisertib (MLN8237). Alisertib is being tested to treat people who have advanced solid tumors or lymphomas for which standard curative or life-prolonging treatment did not exist or was no longer effective or tolerable. This study evaluated the safety and pharmacokinetic (PK) profile, and maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of alisertib, as well as any antitumor activity.

The study enrolled 36 patients. Participants were assigned to one of the two treatment groups and received:

* Alisertib 30 mg
* Alisertib 40 mg All participants took two enteric-coated tablets every 12 hours each day for 7 days followed by a 14-day rest period in a 21-day cycle for up to 16 cycles.

This multi-center trial is conducted in East Asia. The overall time to participate in this study was 24 months, unless it was determined that a participant would derive benefit from continued therapy beyond 24 months. Participants made multiple visits to the clinic, and were contacted up to a maximum of 30 days after last dose of study drug for a follow-up assessment.

A Study of Alisertib (MLN8237) in Adult East Asian Participants With Advanced Solid Tumors or Lymphomas

A Phase 1 Dose Escalation and Pharmacokinetic Study of Alisertib (MLN8237), an Aurora A Kinase Inhibitor, in Adult East Asian Patients With Advanced Solid Tumors or Lymphomas

MTD was defined as highest dose at which \<2 participants experienced a dose-limiting toxicity (DLT). DLT was defined as any of the following events considered possibly related to therapy with alisertib by the investigator: 1. Grade 4 neutropenia (absolute neutrophil count \<500 cells/mm\^3) for \>7 days; 2. Grade 4 neutropenia with fever (oral or ear temperature ≥38.5°C); 3. Grade 4 thrombocytopenia (platelets \<25,000/mm\^3) for \>7 days; 4. Platelet count \<10,000 cells/mm\^3; 5. ≥Grade 3 thrombocytopenia with clinically significant bleeding; 6. Delay in initiation of subsequent cycle by \>7 days due to treatment-related toxicity; 7. ≥Grade 3 nonhematological toxicity except following: a. ≥Grade 3 nausea and/or emesis in the absence of optimal antiemetic therapy; b. ≥Grade 3 diarrhea in the absence of optimal supportive therapy; c. Grade 3 fatigue lasting \<1 week; d. Other Grade 3 nonhematological toxicity that can be safely and reliably controlled to ≤Grade 2 with appropriate treatment.

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 Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

Laboratory AEs in the following system organ classes (SOCs) are reported: blood and lymphatic system disorders, investigations, and metabolism and nutrition disorders. An abnormal laboratory value was assessed as an AE if that value lead to discontinuation or delay in treatment, dose modification, therapeutic intervention, or was considered by the investigator to be a clinically significant change from baseline. A treatment¬-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

Vital signs (blood pressure, pulse rate, and oral temperature) measurements were collected throughout the study.

Dose normalized AUCτ was obtained using AUCτ divided by alisertib dose in milligrams.

Best overall response rate is defined as the percentage of participants with complete response (CR) and/or partial response (PR) as assessed by the Investigator using Lymphoma International Working Group (IWG) Criteria or Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 for target lesions and assessed by CT, PET or MRI. IWG criteria for CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites. RECIST response criteria is defined as: CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter of target lesions.

DOR is defined as the time from the date of first documentation of a CR response to the date of first documentation of PD according to IWG criteria or RECIST criteria 1.1. IWG PD is defined as PD is defined as any new lesion or increase by \>50% of previously involved sites from nadir. RECIST PD is defined as unequivocal progression of existing non-target lesions.

Millennium Pharmaceuticals, Inc.

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.

Alisertib 30 mg

Alisertib 40 mg

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Not Hispanic or Latino

Singapore

Taiwan

Hong Kong

Korea, Republic of

Region of Enrollment

Height

Weight

BSA = square root \[height (cm) x weight (kg)/3600\]

Body Surface Area (BSA)

Safety Population is defined as all participants who received at least one dose of alisertib.

Medical Director

Alisertib 30 mg or 40 mg enteric-coated tablets, orally, twice a day (BID) on Days 1 through 7, followed by a 14-day rest period, in a 21-day cycle (28-day cycle with additional 7-day rest period if all alisertib-related toxicities \[except alopecia\] were not resolved to less than Grade 2), for a maximum of 24 months or until there is evidence of disease progression or unacceptable treatment related toxicity (up to 16 cycles).

Alisertib 30 mg or 40 mg

DLT-Evaluable population is defined as participants with a common race who had not used granulocyte colony-stimulating factor (G-CSF) in cycle 1, and either experienced DLT during Cycle 1 or received at least 85% of planned doses of alisertib and have sufficient follow up data to allow investigator and sponsor to determine whether a DLT occurred.

Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D)

Number of Participants With Adverse Events and Serious Adverse Events

Neutropenia

Anaemia

Thrombocytopenia

Febrile neutropenia

Leukopenia

White blood cell count decreased

Aspartate aminotransferase increased

Neutrophil count decreased

Alanine aminotransferase increased

Platelet count decreased

Blood bilirubin increased

Haemoglobin decreased

Blood creatinine increased

Urine output decreased

Hypokalaemia

Hypercalcaemia

Hyponatraemia

Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events

Hypertension

Hypotension

Bradycardia

Pyrexia

Number of Participants With Clinically Significant Changes in Vital Signs Reported as Adverse Events

Day 1

Day 7

Pharmacokinetic (PK) Population is defined as all participants with sufficient dosing and PK concentration time data to reliably estimate PK parameters. "n" in the category is the number of participants with data available at the given time-point.

Cmax: Maximum Observed Concentration for Alisertib

PK Population is defined as all participants with sufficient dosing and PK concentration time data to reliably estimate PK parameters. "n" in the category is the number of participants with data available at the given time-point.

Tmax: Time to First Occurrence of Cmax for Alisertib

AUCτ: Area Under the Concentration-Time Curve From Time 0 to End of Dosing Interval (τ) for Alisertib

PK Population is defined as all participants with sufficient dosing and PK concentration time data to reliably estimate PK parameters.

Dose Normalized AUCτ: Area Under the Concentration-Time Curve From Time 0 to Time t for Alisertib

T1/2: Terminal Half-Life for Alisertib

Rac: Accumulation Ratio for Alisertib

PTR: Peak Trough Ratio During a Dosing Interval, at Steady State for Alisertib

CLss/F: Apparent Clearance After Extravascular Administration, at Steady State, Calculated Using AUCτ for Alisertib

Best Overall Response Rate Based on Investigator Assessment

Safety Population is defined as all participants who received at least one dose of alisertib. Participants with response were evaluated.

Duration of Response

Data was not analyzed as per the change in planned analysis (protocol amendment).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of Alisertib (MLN8237) in Adult East Asian Participants With Advanced Solid Tumors or Lymphomas	NCT01512758	Advanced Solid ... Lymphomas	Alisertib	18 Years -	Takeda
A Study of Alisertib (MLN8237) in Adult East Asian Participants With Advanced Solid Tumors or Lymphomas	NCT01512758	Advanced Solid ... Lymphomas	Alisertib	18 Years -	Takeda

Spots Global Cancer Trial Database for east asian patients