A Phase 2 Trial of MLN8237, an Oral Aurora A Kinase Inhibitor, in Adult Patients with Acute Myelogenous Leukemia and High-Grade Myelodysplastic Syndrome
- Conditions
- Acute myelogenous leukemia (AML) and high-grade myelodysplastic syndrome (MDS)MedDRA version: 11.1Level: LLTClassification code 10028533Term: <Manually entered code. Term in E.1.1>MedDRA version: 11.1Level: LLTClassification code 10000886Term: <Manually entered code. Term in E.1.1>
- Registration Number
- EUCTR2008-006977-34-FR
- Lead Sponsor
- Millennium Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 57
Each patient must meet all of the following inclusion criteria to be enrolled in the study:
1.Male or female patients 18 years or older
2.Have one of the following diagnoses:
a) Acute myelogenous leukemia (as defined in WHO criteria (28)) with > 10% bone marrow or peripheral blood blasts. This includes leukemia secondary to prior chemotherapy or resulting from an antecedent hematologic disorder, who have failed to achieve CR or relapse after prior therapy and who are not candidates for potentially curative treatment options. Patients who are over age 60 and have not received prior therapy are also eligible, if they are not candidates for standard induction chemotherapy. Patients with acute promyelocytic leukemia (APL) are not eligible.
b) High-grade MDS, defined by all the following features: IPSS Intermediate-2 or High Risk; > 10% blasts on bone marrow examination; treatment failure from, or not candidates for, standard therapies including demethylating agents, eg azacytidine or
decitabine.
3.Eastern Cooperative Oncology Group (ECOG) performance status 0-2
4.Female patients must meet one of the following:
•Postmenopausal for at least one year before the screening visit, or
•Surgically sterile, or
•If they are of childbearing potential, agree to practice two effective methods of contraception from the time of signing of the informed consent form through one month after the last dose of study drug, or agree to completely abstain from heterosexual intercourse.
5.Male patients, even if surgically sterilized (ie, status post-vasectomy) must agree to the following:
•Practice effective barrier contraception during the entire study treatment period and through one month after the last dose of study drug, or completely abstain from heterosexual intercourse.
6.Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
7.Patients who are on hydroxyurea may be included in the study and may continue on hydroxyurea while participating in this study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Patients meeting any of the following exclusion criteria are not to be enrolled in the study.
1.Pregnant or lactating females
2.Known human immunodeficiency virus (HIV) positive or AIDS-related illness
3.Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol
4.Total bilirubin > 1.5 x the upper limit of normal (ULN)
5.Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 x the ULN. AST, ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to their underlying hematological disorder.
6.Calculated creatinine clearance < 30 mL/minute (Cockcroft-Gault formula in Section 14.2 of the protocol)
7.Systemic antineoplastic therapy, including radiotherapy within 14 days preceding the first dose of study drug treatment, except for hydroxyurea
8.Myocardial infarction within 6 months of enrollment or current history of New York Heart Association (NYHA) Class III or IV heart failure (see Section 14.4 of the protocol), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
9.Major surgery within 14 days prior to the first dose of study treatment
10.Clinically uncontrolled central nervous system (CNS) involvement. Patients who have a history of CNS involvement, but no evidence of active CNS disease, are not excluded.
11.Inability to swallow capsules, or inability or unwillingness to avoid taking anything by mouth except for water and prescribed medications for 2 hours before and 1 hour after each dose of MLN8237
12.History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary end point(s): Response rate: partial remission plus complete remission (PR + CR);Main Objective: To estimate antitumor activity of MLN8237 as measured by response rate in patients with AML and high-grade MDS;Secondary Objective: To assess additional measures of antitumor activity, including progression-free survival (PFS) and duration of response (DOR).<br><br>To evaluate the safety and tolerability of MLN8237 treatment based on vital signs, physical examination, laboratory tests, and adverse events.<br>
- Secondary Outcome Measures
Name Time Method