Alisertib in Treating Patients With Myelofibrosis or Relapsed or Refractory Acute Megakaryoblastic Leukemia

• Sponsor: Northwestern University (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02530619
• Collaborator: The Leukemia and Lymphoma Society (Other), Millennium Pharmaceuticals, Inc. (Industry), National Cancer Institute (NCI) (NIH)
• Enrollment: 26
• Locations: 3
• Arm: 1
• Anticipated Duration (Months): 78.7
• Patients Per Site: 8.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety of alisertib and its effect, bad and/or good, on acute megakaryoblastic leukemia (AMKL) or myelofibrosis (MF). The study drug, alisertib, is an investigational drug. An investigational drug is one that has not been approved by the U.S. Food and Drug Administration (FDA). Alisertib has shown evidence in the lab that it may have an effect on a type of cell that produces platelets. This cell is called a megakaryocyte and it is known to be defective (doesn't work well) in both AMKL and MF.

Condition or Disease	Intervention/Treatment	Phase
Acute Megakaryoblastic Leukemia; Myelofibrosis; Primary Myelofibrosis	Drug: Alisertib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the safety profile of alisertib in patients with acute megakaryoblastic leukemia (AMKL) and in patients with myelofibrosis (MF).

SECONDARY OBJECTIVES:

1. Determine preliminary efficacy of alisertib in both populations.

TERCIARY OBJECTIVES:

1. Describe pharmacodynamics (PD) effects of alisertib in peripheral blood and/or bone marrow samples.

2. Evaluate the relationship between biomarker expression levels and response to alisertib.

3. Evaluate reduction in splenomegaly by palpation (MF arm only). IV. Evaluate improvement in MF symptoms (MF arm only), as assessed by the Myeloproliferative Neoplasm Symptom Assessment form (MPN-SAF).

4. Assess change in bone marrow fibrosis in patients in the MF arm.

OUTLINE:

Patients receive alisertib orally (PO) twice daily (BID) on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at approximately 30 days and 6 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-Label, Pilot Study of Alisertib (MLN8237), a Novel Inhibitor of Aurora Kinase A, in Adult Patients With Relapsed/Refractory Acute Megakaryoblastic Leukemia or Myelofibrosis (Including Primary and Post-Essential/Post-Polycythemic Myelofibrosis)
• Actual Study Start Date: Oct 9, 2015
• Actual Primary Completion Date: May 21, 2018
• Anticipated Study Completion Date: May 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (alisertib) Patients receive alisertib PO BID on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Drug: Alisertib; Given PO; Other Names: Aurora A Kinase Inhibitor MLN8237 MLN-8237 MLN8237 ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Safety Profile of Alisertib Per NCI's Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. [From time of treatment to 6 months post discontinuation (range of cycles attempted 1 to 29, median 7.5 cycles, 1 Cycle = 21 days)]

   Adverse events will be defined as those included in CTCAE v 4.0. The AEs that were determined to be at least possibly related to study drug and graded 3, 4, 5 are included here. Grade 1 (mild): the event causes discomfort without disruption of normal daily activities. Grade 2 (moderate): the event causes discomfort that affects normal daily activities. Grade 3 (severe): the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical status. Grade 4 (Life-threatening): the patient was at risk of death at the time of the event. Grade 5 (fatal): the event caused death. All patients who received at least 1 dose of alisertib were considered evaluable for this endpoint.

Secondary Outcome Measures

1. Response to Treatment [Baseline to up to 6 months after the last dose of treatment]

   Serial blood and/or bone marrow samples will be collected at specific timepoints for each disease to determine response to alisertib treatment.

Other Outcome Measures

1. Changes in Biomarker Expression Levels [Baseline to up to 6 months after the last dose of treatment]

   To evaluate the relationship between biomarker expression levels and response. Biomarkers will include a) genes encoding key enzymes in Aurora kinase signaling, b) markers of cellular aneuploidy and apoptosis, and c) markers of megakaryocytic differentiation.

2. Changes in MF Symptoms Assessed by the MPN-SAF (Myeloproliferative Neoplasm Symptom Assessment Form) Score (MF Patients) [Once per cycle (1 cycle=21 days)]

   To evaluate improvement in MF symptoms in the MF arm, changes in symptom scores over time will be calculated.

3. Changes in Pharmacodynamic Effects of Alisertib [Baseline to up to 6 months after the last dose of treatment]

   Serial blood and/or bone marrow samples will be collected at specific timepoints. Flow cytometry, colony forming assays, AURKA autophosphorylation assays, and in vitro cultures of patient specimens to assess the effect of MLN8237 on megakaryocytes and other hematopoietic cells will be measured.

4. Changes in Splenomegaly by Palpation (MF Patients) [Baseline to up to 6 months after the last dose of treatment]

   To evaluate reduction in splenomegaly by palpation in the MF arm. Patients will be examined for splenomegaly by palpation once per cycle and change from baseline will be calculated over time.

5. Change in Bone Marrow Fibrosis (MF Patients) [Screening and up to 54 weeks]

   Assess change in bone marrow fibrosis in patients in the MF arm. Bone marrow will be assessed at screening and after cycle 6 in this population.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• AMKL PATIENTS: Patients must have a confirmed diagnosis of relapsed/refractory acute megakaryoblastic leukemia (AMKL), as defined by World Health Organization (WHO) criteria

• AMKL PATIENTS: Patients must have an Eastern Cooperative Oncology Group (ECOG) status 0-2

• AMKL PATIENTS: Total bilirubin =< 1.5 x upper limit of normal (ULN)

• AMKL PATIENTS: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN

• AMKL PATIENTS: Creatinine < 1.5 x ULN or calculated creatinine clearance > 30 ml/min

• AMKL PATIENTS: Prothrombin time (PT) and partial thromboplastin time (PTT) =< 1.5 x ULN

• AMKL PATIENTS: Absolute neutrophil count (ANC) >= 1500/mm^3

• AMKL PATIENTS: Platelets >= 100,000/mm^3

• AMKL PATIENTS: Hemoglobin > 9 g/dL

• AMKL PATIENTS: Patients must have estimated life expectancy of 6 months or greater

• AMKL PATIENTS: Female patients of child-bearing potential (FOCBP) must have a negative serum beta-human chorionic gonadotropin (HCG) pregnancy test within 7 days prior to registration; NOTE: a FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy

• Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)

• AMKL PATIENTS: Female patients must meet at least one of the following conditions:

• Must be post-menopausal for at least 1 year prior to registration (not of childbearing potential)

• Must be surgically sterilized

• Willing to use an acceptable method of birth control (i.e. hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study

• AMKL PATIENTS: Male patients, even if surgically sterilized (status post-vasectomy) agrees to use an acceptable method for contraception during the entire study treatment period through 4 months after the last dose of alisertib

• AMKL PATIENTS: Patients must be able to understand and willing to sign a written informed consent

• MF PATIENTS: Patients must have a confirmed diagnosis of myelofibrosis (MF), as defined by WHO criteria

• MF PATIENTS: Patients must be intermediate I risk or beyond and meet the following:

• In need of treatment

• Intolerant or refractory to ruxolitinib (or other investigational Janus kinase [JAK]-inhibitors) OR unlikely to benefit from ruxolitinib

• Ineligible for stem cell transplantation

• MF PATIENTS: Patients must have an ECOG status 0-2

• MF PATIENTS: Direct bilirubin < 1.5 x ULN

• MF PATIENTS: ALT/AST =< 2.5 x ULN

• MF PATIENTS: Creatinine < 1.5 x ULN or calculated creatinine clearance > 30 ml/min

• MF PATIENTS: PT and PTT =< 1.5 x ULN

• MF PATIENTS: ANC >= 1500/mm^3

• MF PATIENTS: Platelets >= 100,000/mm^3

• MF PATIENTS: Patients must have estimated life expectancy of 6 months or greater

• MF PATIENTS: Female patients of child-bearing potential (FOCBP) must have a negative serum beta-HCG pregnancy test within 7 days prior to registration

• MF PATIENTS: Female patients must meet at least one of the following conditions:

• Must be post-menopausal for at least 1 year prior to registration (not of childbearing potential)

• Must be surgically sterilized

• Willing to use an acceptable method of birth control (i.e. hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study

• MF PATIENTS: Male patients, even if surgically sterilized (i.e. status post-vasectomy) agrees to use an acceptable method for contraception during the entire study treatment period through 4 months after the last dose of alisertib

• MF PATIENTS: Patients must be able to understand and willing to sign a written informed consent

Exclusion Criteria:

• Patients who have received treatment with clinically significant enzyme inducers (such as enzyme inducing antiepileptic drugs phenytoin, carbamazepine, or phenobarbital, or rifampin, rifabutin, rafapentine, or St. John's wort) within 14 days prior to registration are not eligible

• Patients who have received any investigational products, antineoplastic therapies, or radiotherapy within 14 days prior to registration are not eligible; NOTE: patients actively receiving hydroxyurea are eligible and may continue to receive hydroxyurea through cycle 1 of protocol treatment

• Patients who have received prior administration of an Aurora A kinase targeted agent (including alisertib) are not eligible

• Patients who have received corticosteroids within 7 days prior registration are not eligible, UNLESS the patient has been taking a continuous dose of no more than 15 mg/day of prednisone for at least 1 month prior; NOTE: low dose steroid use for control of nausea and vomiting will be allowed; topical steroid use and inhaled steroids are also permitted

• Patients who are candidates (eligible and willing) for standard and/or potentially curative treatments are not eligible

• Patients who have had received radiation therapy to more than 25% of the bone marrow are not eligible (whole pelvic radiation is considered to be over 25%)

• Patients who have had major surgery within one month (28 days) prior to registration are not eligible

• Patients who have had prior allogenic bone marrow or organ transplantation are not eligible

• Patients who have had grade 2 or higher diarrhea, despite optimal antidiarrheal supportive care, within 7 days prior to registration are not eligible

• Patients who have had grade 2 or higher peripheral neuropathy within 14 days prior to registration are not eligible

• Patients who have had a myocardial infarction within 6 months (24 weeks) prior to registration are not eligible

• Patients who have class III or IV heart failure (as defined by the New York Heart Association), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities are not eligible

• Patients who have known gastrointestinal (GI) disease or GI procedures which could interfere with the oral absorption or tolerance of alisertib are not eligible; examples include (but are not limited to) partial gastrectomy, history of small intestine surgery, and celiac disease

• Patients who have a known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness (such as severe chronic obstructive pulmonary disease or requirement for supplemental oxygen) are not eligible

• Patients who have a requirement for constant administration of proton pump inhibitor, histamine-2 (H2) antagonist, or pancreatic enzymes are not eligible; intermittent usage of antacids or H2 antagonists are allowed

• Patients who have a systemic infection requiring intravenous (IV) antibiotic therapy within 14 days prior to registration (or other severe infection) are not eligible

• Patients who are known human immunodeficiency virus (HIV) positive are not eligible

• Patients who are known hepatitis B surface antigen positive are not eligible

• Patients who have known or suspected active hepatitis C infections are not eligible; NOTE: patients who are hepatitis C surface antigen positive are eligible

• Female patients who are pregnant or breast feeding are not eligible

• Patients who have a severe acute or chronic medical or psychiatric condition, including uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement for pancreatic enzymes, any condition that would modify small bowel absorption of oral medications, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study are not eligible

• Patients who have symptomatic central nervous system (CNS) involvement are not eligible

• Patients who have been diagnosed or treated for another malignancy within 3 years prior to registration are not eligible aside from these exceptions: completely resected basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy

• Patients who are unable to swallow oral medication or are unwilling to comply with the administration requirements are not eligible

• Patients who require administration of myeloid growth factors or platelet transfusions within 14 days prior to registration are not eligible

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
2	Northwestern University	Chicago	Illinois	United States	60611
3	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Northwestern University
• The Leukemia and Lymphoma Society
• Millennium Pharmaceuticals, Inc.
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Brady Stein, MD, Northwestern University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 4, 2019

More Information

Publications

None provided.

• Responsible Party: Brady Stein, Principal Investigator, Northwestern University
• ClinicalTrials.gov Identifier: NCT02530619
• Other Study ID Numbers: NU 15H10; NCI-2015-01219; STU00200682; NU 15H10; P30CA060553
• First Posted: Aug 21, 2015
• Last Update Posted: May 26, 2021
• Last Verified: May 1, 2021

• Additional relevant MeSH terms: Leukemia; Leukemia, Megakaryoblastic, Acute; Primary Myelofibrosis

Study Results

Participant Flow

Recruitment Details	The study opened for accrual on October 09, 2015 with an accrual goal of 24 patients. The first patient started treatment July 05, 2016. The study closed to further accrual on November 02, 2017 with total accrual having been met.

Arm/Group Title	Alisertib 50 mg BID
Arm/Group Description	Patients receive alisertib PO BID on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Alisertib: Administered orally 50 mg BID on days 1-7 of each cycle; one cycle is defined as 21 days (days 8-21 will be rest days). Patients may continue to receive cycles of alisertib until progression of disease or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Period Title: Registered for Study
STARTED	26
Registered	26
Received 1st Dose of Alisertib	24
COMPLETED	24
NOT COMPLETED	2
Period Title: Registered for Study
STARTED	24
COMPLETED	24
NOT COMPLETED	0
Period Title: Registered for Study
STARTED	24
COMPLETED	14
NOT COMPLETED	10
Period Title: Registered for Study
STARTED	14
COMPLETED	14
NOT COMPLETED	0
Period Title: Registered for Study
STARTED	21
COMPLETED	10
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	Alisertib 50 mg BID
Arm/Group Description	Patients receive alisertib PO BID on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Alisertib: Administered orally 50 mg BID on days 1-7 of each cycle; one cycle is defined as 21 days (days 8-21 will be rest days). Patients may continue to receive cycles of alisertib until progression of disease or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Overall Participants	24
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 25%
>=65 years	18 75%
Sex: Female, Male (Count of Participants)
Female	8 33.3%
Male	16 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 4.2%
Not Hispanic or Latino	23 95.8%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 4.2%
White	22 91.7%
More than one race	0 0%
Unknown or Not Reported	1 4.2%
Region of Enrollment (participants) [Number]
United States	24 100%
Refractory Acute Megakaryoblastic Leukemia or Myelofibrosis (Count of Participants)
Myelofibrosis	24 100%
Refractory Acute Megakaryoblastic Leukemia	0 0%

Outcome Measures

1. Primary Outcome

Title	Safety Profile of Alisertib Per NCI's Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
Description	Adverse events will be defined as those included in CTCAE v 4.0. The AEs that were determined to be at least possibly related to study drug and graded 3, 4, 5 are included here. Grade 1 (mild): the event causes discomfort without disruption of normal daily activities. Grade 2 (moderate): the event causes discomfort that affects normal daily activities. Grade 3 (severe): the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical status. Grade 4 (Life-threatening): the patient was at risk of death at the time of the event. Grade 5 (fatal): the event caused death. All patients who received at least 1 dose of alisertib were considered evaluable for this endpoint.
Time Frame	From time of treatment to 6 months post discontinuation (range of cycles attempted 1 to 29, median 7.5 cycles, 1 Cycle = 21 days)

Outcome Measure Data

Analysis Population Description

Data was collected from all patients for the primary endpoint until May 2018 when it was determined there was sufficient data collected for primary endpoint analysis and primary endpoint was determined to be met. At the time of data cut off, 7 patients remained on active treatment and range of cycles completed by patients was 1-29 (median 7.5 cycles). No further data was collected after May 2018 for primary outcome measure purposes.

Arm/Group Title	Alisertib 50 mg BID
Arm/Group Description	Patients receive alisertib PO BID on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Alisertib: Administered orally 50 mg BID on days 1-7 of each cycle; one cycle is defined as 21 days (days 8-21 will be rest days). Patients may continue to receive cycles of alisertib until progression of disease or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
Measure Participants	24
Neutropenia Grade 3	5 20.8%
Neutropenia Grade 4	5 20.8%
Febrile Neutropenia Grade 3	1 4.2%
Lymphocytopenia Grade 3	9 37.5%
Thrombocytopenia Grade 3	5 20.8%
Thrombocytopenia Grade 4	2 8.3%
Anemia Grade 3	5 20.8%
Vertigo Grade 3	1 4.2%
Diarrhea Grade 3	1 4.2%
Alanine aminotransferase increased Grade 3	1 4.2%
Creatinine increased Grade 3	1 4.2%

2. Secondary Outcome

Title	Response to Treatment
Description	Serial blood and/or bone marrow samples will be collected at specific timepoints for each disease to determine response to alisertib treatment.
Time Frame	Baseline to up to 6 months after the last dose of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Other Pre-specified Outcome

Title	Changes in Biomarker Expression Levels
Description	To evaluate the relationship between biomarker expression levels and response. Biomarkers will include a) genes encoding key enzymes in Aurora kinase signaling, b) markers of cellular aneuploidy and apoptosis, and c) markers of megakaryocytic differentiation.
Time Frame	Baseline to up to 6 months after the last dose of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Other Pre-specified Outcome

Title	Changes in MF Symptoms Assessed by the MPN-SAF (Myeloproliferative Neoplasm Symptom Assessment Form) Score (MF Patients)
Description	To evaluate improvement in MF symptoms in the MF arm, changes in symptom scores over time will be calculated.
Time Frame	Once per cycle (1 cycle=21 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Other Pre-specified Outcome

Title	Changes in Pharmacodynamic Effects of Alisertib
Description	Serial blood and/or bone marrow samples will be collected at specific timepoints. Flow cytometry, colony forming assays, AURKA autophosphorylation assays, and in vitro cultures of patient specimens to assess the effect of MLN8237 on megakaryocytes and other hematopoietic cells will be measured.
Time Frame	Baseline to up to 6 months after the last dose of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	Changes in Splenomegaly by Palpation (MF Patients)
Description	To evaluate reduction in splenomegaly by palpation in the MF arm. Patients will be examined for splenomegaly by palpation once per cycle and change from baseline will be calculated over time.
Time Frame	Baseline to up to 6 months after the last dose of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	Change in Bone Marrow Fibrosis (MF Patients)
Description	Assess change in bone marrow fibrosis in patients in the MF arm. Bone marrow will be assessed at screening and after cycle 6 in this population.
Time Frame	Screening and up to 54 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse Events (AEs) were collected over a 5 year period. Each patient was followed from the time of treatment, during treatment at the beginning of each cycle through 6 months post last treatment. 1 cycle = 21 days. Serious Adverse Events (SAEs) are reported from the time of treatment initiation. The range of cycles attempted was 1-38. At the time of reporting this data, 3 patients remain on treatment.
Arm/Group Title	Alisertib 50 mg BID
Arm/Group Description	Patients receive alisertib PO BID on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Alisertib: Administered orally 50 mg BID on days 1-7 of each cycle; one cycle is defined as 21 days (days 8-21 will be rest days). Patients may continue to receive cycles of alisertib until progression of disease or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
All Cause Mortality
	Alisertib 50 mg BID
	Affected / at Risk (%)	# Events
Total	5/24 (20.8%)
Serious Adverse Events
	Alisertib 50 mg BID
	Affected / at Risk (%)	# Events
Total	8/24 (33.3%)
Blood and lymphatic system disorders
Febrile neutropenia	1/24 (4.2%)
Anemia	1/24 (4.2%)
Anemia	1/24 (4.2%)
Leukocytosis	1/24 (4.2%)
Neutropenic fever	1/24 (4.2%)
Cardiac disorders
Non- ST Myocardial Infarction (NSTEMI)	1/24 (4.2%)
Gastrointestinal disorders
diarrhea	1/24 (4.2%)
Infections and infestations
Upper Respiratory Infection - parainfluenza	1/24 (4.2%)
Lung infection	1/24 (4.2%)
Cellulitis	1/24 (4.2%)
Respiratory, thoracic and mediastinal disorders
pneumonia	1/24 (4.2%)
Pneumonitis	1/24 (4.2%)
Vascular disorders
pulmonary embolism	1/24 (4.2%)
Other (Not Including Serious) Adverse Events
	Alisertib 50 mg BID
	Affected / at Risk (%)	# Events
Total	24/24 (100%)
Blood and lymphatic system disorders
Anemia	11/24 (45.8%)
Febrile neutropenia	2/24 (8.3%)
Raynaud Syndrome	1/24 (4.2%)
Hematoma	1/24 (4.2%)
Cardiac disorders
Atrial fibrillation	1/24 (4.2%)
Chest pain - cardiac	1/24 (4.2%)
Myocardial infarction	1/24 (4.2%)
Palpitations	1/24 (4.2%)
Sinus bradycardia	2/24 (8.3%)
Sinus tachycardia	1/24 (4.2%)
Ventricular arrhythmia	1/24 (4.2%)
Systolic murmur	1/24 (4.2%)
cardiomegaly	1/24 (4.2%)
Murmur	1/24 (4.2%)
Ear and labyrinth disorders
Ear pain	1/24 (4.2%)
Vertigo	2/24 (8.3%)
Decreased Hearing	1/24 (4.2%)
Eye disorders
Blurred vision	1/24 (4.2%)
conjunctivae erythema	1/24 (4.2%)
eye bruising and edema	1/24 (4.2%)
Retinal Hemmorhage	1/24 (4.2%)
eye redness	1/24 (4.2%)
periorbital bruising	1/24 (4.2%)
Gastrointestinal disorders
Abdominal pain	8/24 (33.3%)
Constipation	7/24 (29.2%)
Diarrhea	11/24 (45.8%)
Dry mouth	1/24 (4.2%)
Dyspepsia	1/24 (4.2%)
Gastroesophageal reflux disease	1/24 (4.2%)
Gastrointestinal pain	1/24 (4.2%)
Mucositis oral	5/24 (20.8%)
Nausea	10/24 (41.7%)
Vomiting	4/24 (16.7%)
Blood in stool	1/24 (4.2%)
General disorders
Chills	3/24 (12.5%)
Edema face	1/24 (4.2%)
Edema limbs	7/24 (29.2%)
Fatigue	9/24 (37.5%)
Fever	4/24 (16.7%)
Flu like symptoms	2/24 (8.3%)
Gait disturbance	1/24 (4.2%)
Non-cardiac chest pain	1/24 (4.2%)
Pain	5/24 (20.8%)
polydipsia	1/24 (4.2%)
prostatomegaly	1/24 (4.2%)
Popliteal fossa cysts	1/24 (4.2%)
Hepatobiliary disorders
Gallstones	1/24 (4.2%)
Infections and infestations
Bronchial infection	1/24 (4.2%)
Lung infection	1/24 (4.2%)
Rhinitis infective	1/24 (4.2%)
Sinusitis	2/24 (8.3%)
Upper respiratory infection	3/24 (12.5%)
rhinorrhea	1/24 (4.2%)
C difficile positive	1/24 (4.2%)
Cellulitis	1/24 (4.2%)
tinea pedis	1/24 (4.2%)
Injury, poisoning and procedural complications
Bruising	7/24 (29.2%)
Fall	4/24 (16.7%)
Wound complication	1/24 (4.2%)
Wrist fracture	1/24 (4.2%)
Pain in the bone marrow site	1/24 (4.2%)
Investigations
Activated partial thromboplastin time prolonged	5/24 (20.8%)
Alanine aminotransferase increased	9/24 (37.5%)
Alkaline phosphatase increased	10/24 (41.7%)
Aspartate aminotransferase increased	9/24 (37.5%)
Blood bilirubin increased	6/24 (25%)
Creatinine increased	9/24 (37.5%)
Electrocardiogram QT corrected interval prolonged	1/24 (4.2%)
INR increased	4/24 (16.7%)
Lymphocyte count decreased	17/24 (70.8%)
Neutrophil count decreased	14/24 (58.3%)
Platelet count decreased	16/24 (66.7%)
White blood cell decreased	14/24 (58.3%)
Night Sweats	1/24 (4.2%)
Metabolism and nutrition disorders
Anorexia	7/24 (29.2%)
Dehydration	1/24 (4.2%)
Hypercalcemia	1/24 (4.2%)
Hyperglycemia	16/24 (66.7%)
Hyperkalemia	5/24 (20.8%)
Hypermagnesemia	1/24 (4.2%)
Hypernatremia	1/24 (4.2%)
Hyperuricemia	7/24 (29.2%)
Hypoalbuminemia	11/24 (45.8%)
Hypocalcemia	13/24 (54.2%)
Hypoglycemia	1/24 (4.2%)
Hypomagnesemia	2/24 (8.3%)
Hyponatremia	8/24 (33.3%)
Hypophosphatemia	1/24 (4.2%)
Appetite increased	1/24 (4.2%)
Musculoskeletal and connective tissue disorders
Arthritis	2/24 (8.3%)
Back pain	2/24 (8.3%)
Bone pain	4/24 (16.7%)
Generalized muscle weakness	4/24 (16.7%)
Myalgia	2/24 (8.3%)
Myositis	1/24 (4.2%)
Neck pain	2/24 (8.3%)
Osteoporosis	1/24 (4.2%)
Pain in extremity	6/24 (25%)
metatarsalgia	1/24 (4.2%)
Leg cramps	1/24 (4.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small Squamous cell carcinoma	1/24 (4.2%)
Nervous system disorders
Concentration impairment	1/24 (4.2%)
Dizziness	7/24 (29.2%)
Encephalopathy	1/24 (4.2%)
Headache	4/24 (16.7%)
Memory impairment	1/24 (4.2%)
Paresthesia	1/24 (4.2%)
Peripheral motor neuropathy	2/24 (8.3%)
Presyncope	2/24 (8.3%)
Tremor	2/24 (8.3%)
Psychiatric disorders
Anxiety	1/24 (4.2%)
Depression	1/24 (4.2%)
Insomnia	4/24 (16.7%)
Mood Swings	2/24 (8.3%)
Renal and urinary disorders
Chronic kidney disease	1/24 (4.2%)
Urinary retention	1/24 (4.2%)
Urinary urgency	1/24 (4.2%)
Dysuria	1/24 (4.2%)
renal cysts	1/24 (4.2%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/24 (4.2%)
Aspiration	1/24 (4.2%)
Atelectasis	1/24 (4.2%)
Cough	4/24 (16.7%)
Dyspnea	4/24 (16.7%)
Epistaxis	1/24 (4.2%)
Laryngeal edema	1/24 (4.2%)
Nasal congestion	2/24 (8.3%)
Pleural effusion	3/24 (12.5%)
Pneumonitis	1/24 (4.2%)
Pulmonary hypertension	1/24 (4.2%)
Respiratory synctial virus	1/24 (4.2%)
Rhinitis	1/24 (4.2%)
Skin and subcutaneous tissue disorders
Alopecia	13/24 (54.2%)
Dry skin	1/24 (4.2%)
Erythema multiforme	1/24 (4.2%)
Nail loss	1/24 (4.2%)
Pain of skin	1/24 (4.2%)
Pruritus	4/24 (16.7%)
Rash acneiform	2/24 (8.3%)
Rash maculo-papular	4/24 (16.7%)
Tear	1/24 (4.2%)
skin nodules	1/24 (4.2%)
Rash	1/24 (4.2%)
facial hair loss	1/24 (4.2%)
shoulder cyst	1/24 (4.2%)
Vascular disorders
Hot flashes	1/24 (4.2%)
Hypertension	9/24 (37.5%)
Thromboembolic event	1/24 (4.2%)
calcifications	1/24 (4.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.