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Status unknownNCT02530619Updated May 26, 2021Results posted

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

An interventional study of Alisertib and Laboratory Biomarker Analysis in Acute Megakaryoblastic Leukemia, Myelofibrosis and Primary Myelofibrosis, sponsored by Northwestern University. Status unknown at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-05-26.

Sponsored by Northwestern University · Not applicable, Interventional, and Treatment

The sponsor has not verified this record recently (last verified May 2021), so the status shown — last known as Active, not recruiting — may be out of date.
Phase
Not applicable
Study type
Interventional
Enrollment
26
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the detailed description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

I. Determine preliminary efficacy of alisertib in both populations.

TERCIARY OBJECTIVES:

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

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

III. 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).

V. 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.

02

Conditions studied

  • Acute Megakaryoblastic Leukemia
  • Myelofibrosis
  • Primary Myelofibrosis
03

In context

Leukemia

5,442 studies on the registry are indexed under Leukemia; 637 are open to participants now.

This study's enrollment of 26 is below the median of 38 across 4,248 interventional studies indexed under Leukemia.

Browse Leukemia studies →

Lead sponsor

Northwestern University is the lead sponsor of 1,396 studies on the registry; 199 are open to participants now.

Of its 102 completed or terminated interventional studies of FDA-regulated products, 73 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
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

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
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
26 participants (actual)

Study arms

  • 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 · Other: Laboratory Biomarker Analysis · Other: Pharmacological Study

Interventions

  • DrugAlisertib

    Given PO

    Also known as: Aurora A Kinase Inhibitor MLN8237, MLN-8237, MLN8237

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • OtherPharmacological Study

    Correlative studies

06

What researchers measure

Primary outcomes

  1. Safety Profile of Alisertib Per NCI's Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.

    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)

Secondary outcomes

  1. Response to Treatment

    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

Other outcomes

  1. Changes in Biomarker Expression Levels

    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

  2. Changes in MF Symptoms Assessed by the MPN-SAF (Myeloproliferative Neoplasm Symptom Assessment Form) Score (MF Patients)

    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)

  3. Changes in Pharmacodynamic Effects of Alisertib

    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

  4. Changes in Splenomegaly by Palpation (MF Patients)

    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

  5. Change in Bone Marrow Fibrosis (MF Patients)

    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

07

Results

Posted Dec 19, 2020

Participant flow

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.

Registered for Study
Participant flow — Registered for Study
MilestoneAlisertib 50 mg BID
Started26
Registered26
Received 1st dose of alisertib24
Completed24
Not completed2
Withdrew: Withdrawal by subject2
Completed 1st Cycle of Treatment
Participant flow — Completed 1st Cycle of Treatment
MilestoneAlisertib 50 mg BID
Started24
Completed24
Not completed0
Continued Treatment Cycles 2 Through 6
Participant flow — Continued Treatment Cycles 2 Through 6
MilestoneAlisertib 50 mg BID
Started24
Completed14
Not completed10
Withdrew: Adverse event2
Withdrew: Withdrawal by subject2
Withdrew: Progressive disease4
Withdrew: Lack of efficacy2
Continued Treatment Cycle 7+
Participant flow — Continued Treatment Cycle 7+
MilestoneAlisertib 50 mg BID
Started14
Completed14
Not completed0
Follow-up Period (6 Months)
Participant flow — Follow-up Period (6 Months)
MilestoneAlisertib 50 mg BID
Started21
Completed10
Not completed11
Withdrew: Death4
Withdrew: Lost to follow-up2
Withdrew: Withdrawal by subject5

Outcome measures

PrimarySafety Profile of Alisertib Per NCI's Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.

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)
Reported as:
Count of participants · Participants
Safety Profile of Alisertib Per NCI's Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
ParticipantsAlisertib 50 mg BID
Neutropenia Grade 35
Neutropenia Grade 45
Febrile Neutropenia Grade 31
Lymphocytopenia Grade 39
Thrombocytopenia Grade 35
Thrombocytopenia Grade 42
Anemia Grade 35
Vertigo Grade 31
Diarrhea Grade 31
Alanine aminotransferase increased Grade 31
Creatinine increased Grade 31
SecondaryResponse to Treatment

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

Results for this outcome have not been posted.

Other pre-specifiedChanges in Biomarker Expression Levels

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

Results for this outcome have not been posted.

Other pre-specifiedChanges in MF Symptoms Assessed by the MPN-SAF (Myeloproliferative Neoplasm Symptom Assessment Form) Score (MF Patients)

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)

Results for this outcome have not been posted.

Other pre-specifiedChanges in Pharmacodynamic Effects of Alisertib

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

Results for this outcome have not been posted.

Other pre-specifiedChanges in Splenomegaly by Palpation (MF Patients)

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

Results for this outcome have not been posted.

Other pre-specifiedChange in Bone Marrow Fibrosis (MF Patients)

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

Results for this outcome have not been posted.

Adverse events

Collected over 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.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Alisertib 50 mg BID5/24 (20.8%)8/24 (33.3%)24/24 (100%)
Most frequent serious events
Showing 10 of 13
Most frequent serious events
EventAlisertib 50 mg BID
Upper Respiratory Infection - parainfluenzaInfections and infestations1/24
pneumoniaRespiratory, thoracic and mediastinal disorders1/24
Lung infectionInfections and infestations1/24
Febrile neutropeniaBlood and lymphatic system disorders1/24
CellulitisInfections and infestations1/24
PneumonitisRespiratory, thoracic and mediastinal disorders1/24
Non- ST Myocardial Infarction (NSTEMI)Cardiac disorders1/24
pulmonary embolismVascular disorders1/24
AnemiaBlood and lymphatic system disorders1/24
diarrheaGastrointestinal disorders1/24
Most frequent other events
Showing 10 of 149
Most frequent other events
EventAlisertib 50 mg BID
Lymphocyte count decreasedInvestigations17/24
Platelet count decreasedInvestigations16/24
HyperglycemiaMetabolism and nutrition disorders16/24
Neutrophil count decreasedInvestigations14/24
White blood cell decreasedInvestigations14/24
HypocalcemiaMetabolism and nutrition disorders13/24
AlopeciaSkin and subcutaneous tissue disorders13/24
AnemiaBlood and lymphatic system disorders11/24
DiarrheaGastrointestinal disorders11/24
HypoalbuminemiaMetabolism and nutrition disorders11/24

Baseline characteristics

Two patients were registered to the study, but never received any study drug (alisertib). These two patients are excluded from demographics.

Age, Categorical
Age, Categorical(Participants)Alisertib 50 mg BID
<=18 years0
Between 18 and 65 years6
>=65 years18
Sex: Female, Male
Sex: Female, Male(Participants)Alisertib 50 mg BID
Female8
Male16
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Alisertib 50 mg BID
Hispanic or Latino1
Not Hispanic or Latino23
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Alisertib 50 mg BID
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American1
White22
More than one race0
Unknown or Not Reported1
Region of Enrollment
Region of Enrollment(participants)Alisertib 50 mg BID
United States24
Refractory Acute Megakaryoblastic Leukemia or Myelofibrosis
Refractory Acute Megakaryoblastic Leukemia or Myelofibrosis(Participants)Alisertib 50 mg BID
Myelofibrosis24
Refractory Acute Megakaryoblastic Leukemia0
08

Study locations

3 sites
  • University of Miami Miller School of Medicine-Sylvester Cancer Center
    Miami, Florida 33136, United States
  • Northwestern University
    Chicago, Illinois 60611, United States
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Feb 4, 2019

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 26, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02530619
Lead sponsor
Northwestern University
Collaborators
The Leukemia and Lymphoma Society, Millennium Pharmaceuticals, Inc., National Cancer Institute (NCI)
Responsible party
Brady Stein (Principal Investigator, Northwestern University) — Principal investigator
First posted
Aug 21, 2015
Start date
Oct 9, 2015
Primary completion
May 21, 2018
Completion
May 2022 (estimated)
Results posted
Dec 19, 2020
Last update
May 26, 2021

Study contacts

Brady Stein, MD
principal investigator · Northwestern University

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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