Acute Megakaryoblastic LeukemiaNCT02530619
Alisertib in Treating Patients With Myelofibrosis or Relapsed or Refractory Acute Megakaryoblastic Leukemia
A study testing Alisertib, Laboratory Biomarker Analysis and Pharmacological Study in people with Acute Megakaryoblastic Leukemia and Myelofibrosis, run by Northwestern University at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Megakaryoblastic Leukemia, Myelofibrosis, Primary Myelofibrosis
- What is being tested?
- Alisertib, Laboratory Biomarker Analysis and Pharmacological Study
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 3 sitesUnited States
- Study dates
- 9 Oct 2015to May 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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%)
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- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Northwestern University
Chicago, Illinois, 60611
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Mayo Clinic
Rochester, Minnesota, 55905
About this study
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)
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:
- Determine the safety profile of alisertib in patients with acute megakaryoblastic leukemia (AMKL) and in patients with myelofibrosis (MF).
SECONDARY OBJECTIVES:
- Determine preliminary efficacy of alisertib in both populations.
TERCIARY OBJECTIVES:
- 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).
- 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.
- Being tested
- Alisertib, Laboratory Biomarker Analysis, Pharmacological Study
- Medical subject headings
- Leukemia, Megakaryoblastic, Acute, Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlisertibDrug
Also called Aurora A Kinase Inhibitor MLN8237, MLN-8237, MLN8237
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (alisertib) | Experimental | Patients receive alisertib PO BID on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: Alisertib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline to up to 6 months after the last dose of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2015 (estimated)
- Study start9 Oct 2015
- Primary completion21 May 2018
- Study completionMay 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Megakaryoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- The Leukemia and Lymphoma Society, Millennium Pharmaceuticals, Inc., National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Brady Stein, Northwestern University
- Investigators
- Brady Stein, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02530619
- Sponsor's protocol ID
- NU 15H10
- Other IDs
- NCI-2015-01219, STU00200682, NU 15H10, P30CA060553
- Status last verified
- May 2021
- First submitted
- 18 Aug 2015
- Last updated
- 26 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02530619
- Acronym / sponsor ID
- NU 15H10
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- The Leukemia and Lymphoma Society, Millennium Pharmaceuticals, Inc., National Cancer Institute (NCI)
- Study start
- 9 Oct 2015 (actual)
- Primary completion
- 21 May 2018 (actual)
- Study completion
- May 2022 (estimated)
- First posted
- 21 Aug 2015 (estimated)
- Results
- Posted 19 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- Determine the safety profile of alisertib in patients with acute megakaryoblastic leukemia (AMKL) and in patients with myelofibrosis (MF).
SECONDARY OBJECTIVES:
- Determine preliminary efficacy of alisertib in both populations.
TERCIARY OBJECTIVES:
- 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).
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (alisertib) | Experimental | Drug: Alisertib, Other: Laboratory Biomarker Analysis, Other: Pharmacological StudyPatients receive alisertib PO BID on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (39 listed)
- 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
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlisertibAlso: Aurora A Kinase Inhibitor MLN8237, MLN-8237, MLN8237Given PO | Drug | Treatment (alisertib) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (alisertib) |
| Pharmacological StudyCorrelative studies | Other | Treatment (alisertib) |
Primary outcome
Safety Profile of Alisertib Per NCI's Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
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)
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.
1 secondary outcome
Response to Treatment
Time frame: Baseline to up to 6 months after the last dose of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brady Stein, MD principal investigator
Northwestern University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Alisertib, Laboratory Biomarker Analysis and Pharmacological Study in people with Acute Megakaryoblastic Leukemia and Myelofibrosis, run by Northwestern University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 39 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety Profile of Alisertib Per NCI's Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. (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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2021.