Alisertib in Treating Patients With Myelofibrosis or Relapsed or Refractory Acute Megakaryoblastic Leukemia
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|ClinicalTrials.gov Identifier: NCT02530619|
Recruitment Status : Active, not recruiting
First Posted : August 21, 2015
Results First Posted : December 19, 2020
Last Update Posted : May 26, 2021
|Condition or disease||Intervention/treatment||Phase|
|Acute Megakaryoblastic Leukemia Myelofibrosis Primary Myelofibrosis||Drug: Alisertib Other: Laboratory Biomarker Analysis Other: Pharmacological Study||Not Applicable|
I. Determine the safety profile of alisertib in patients with acute megakaryoblastic leukemia (AMKL) and in patients with myelofibrosis (MF).
I. Determine preliminary efficacy of alisertib in both populations.
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.
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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 :||October 9, 2015|
|Actual Primary Completion Date :||May 21, 2018|
|Estimated Study Completion Date :||May 2022|
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.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- 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.
- Response to Treatment [ Time Frame: 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.
- Changes in Biomarker Expression Levels [ Time Frame: 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.
- Changes in MF Symptoms Assessed by the MPN-SAF (Myeloproliferative Neoplasm Symptom Assessment Form) Score (MF Patients) [ Time Frame: 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.
- Changes in Pharmacodynamic Effects of Alisertib [ Time Frame: 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.
- Changes in Splenomegaly by Palpation (MF Patients) [ Time Frame: 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.
- Change in Bone Marrow Fibrosis (MF Patients) [ Time Frame: 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02530619
|United States, Florida|
|University of Miami Miller School of Medicine-Sylvester Cancer Center|
|Miami, Florida, United States, 33136|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Brady Stein, MD||Northwestern University|