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

NCT02530619 | Unknown Results DMC

• 4 other identifiers: NU 15H10NCI-2015-01219STU00200682P30CA060553
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

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.

Conditions

Acute Megakaryoblastic Leukemia; Myelofibrosis; Primary Myelofibrosis

Outcome Measures

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.

  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

  Baseline to up to 6 months after the last dose of treatment

Other Outcomes (5)

• Changes in Biomarker Expression Levels

  Baseline to up to 6 months after the last dose of treatment

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

  Once per cycle (1 cycle=21 days)

• Changes in Pharmacodynamic Effects of Alisertib

  Baseline to up to 6 months after the last dose of treatment

Study Arms (1)

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.

Drug: Alisertib; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

Interventions

Alisertib DRUG

Given PO

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

Treatment (alisertib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (alisertib)

Pharmacological Study OTHER

Correlative studies

Treatment (alisertib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (3)

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Leukemia, Megakaryoblastic, Acute; Primary Myelofibrosis

Interventions

MLN 8237

Condition Hierarchy (Ancestors)

Leukemia, Myeloid, Acute; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases

Results Point of Contact

• Title: Brady L. Stein, MD
• Organization: Northwestern University, Feinberg School of Medicine

bstein@nmff.org

312-695-6832

Study Officials

• Brady Stein, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 18, 2015
• First Posted: August 21, 2015
• Study Start: October 9, 2015
• Primary Completion: May 21, 2018
• Study Completion: May 1, 2022
• Last Updated: May 26, 2021
• Results First Posted: December 19, 2020

Record last verified: 2021-05

Locations

US (3)