A Phase 2 Trial of MLN8237 in Adult Participants With Acute Myelogenous Leukemia and High-Grade Myelodysplastic Syndrome
2018년 4월 9일 업데이트: Millennium Pharmaceuticals, Inc.
A Phase 2 Trial of MLN8237, an Oral Aurora A Kinase Inhibitor, in Adult Patients With Acute Myelogenous Leukemia and High-Grade Myelodysplastic Syndrome
This is an open-label, multicenter, phase 2 study of alisertib (MLN8237) in participants with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
연구 개요
상세 설명
The drug being tested in this study is called alisertib (MLN8237). Alisertib is being tested to treat people who have acute myeloid leukemia (AML) or high-grade myelodysplastic syndrome (MDS). This study looked at the antitumor activity in people who received alisertib.
The study enrolled 57 patients. Participants were categorized by disease sub-types AML and MDS. Participants received:
• Alisertib 50 mg
All participants took alisertib capsules every 12 hours each day for 7 days followed by a 14-day rest period in 21-day cycles for approximately 26 cycles.
This multi-center trial was conducted in North America and France. The overall time to participate in this study was until there is evidence of disease progression or unacceptable treatment-related toxicity. The participant could continue treatment beyond 12 months if it was considered by the Sponsor and the Investigator that they would derive benefit from continued alisertib treatment. Participants had weekly blood work and clinic visits, with disease assessments every 2 cycles (ie. every 6 weeks) up to and including Cycle 16. Reduced visits (every 12 weeks) were conducted for participants tolerating treatment beyond Cycle 16 and for participants off treatment without disease progression.
연구 유형
중재적
등록 (실제)
57
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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New Jersey
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Morristown, New Jersey, 미국, 07962
- Hematology and Oncology Associates of Northern New Jersey
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria:
Each participants must meet all of the following inclusion criteria:
- Male or female participants 18 years or older
Eligible diagnoses:
- Acute myelogenous leukemia (except acute promyelocytic leukemia [APL]) with > 10% bone marrow or peripheral blood blasts; failed to achieve complete response (CR) or relapse after prior therapy, not candidates for potentially curative treatment. Untreated participants > 60 are eligible if not candidates for standard induction.
- High-grade myelodysplastic syndrome (MDS), defined by all the following features: International Prognostic Scoring System (IPSS) Intermediate-2 or High Risk; > 10% blasts on bone marrow examination; treatment failure from, or not candidates for, standard therapies including demethylating agents, e.g. azacytidine or decitabine.
- Eastern Cooperative Oncology Group performance status 0-2
Female participants:
- Postmenopausal for at least one year
- Surgically sterile, or
- If childbearing potential, agree to practice two effective methods of contraception or abstain from heterosexual intercourse.
Male participants:
- Practice effective barrier contraception to one month after the last dose of study drug, or
- Abstain from heterosexual intercourse.
- Voluntary written consent
- Participants on hydroxyurea may be included
Exclusion Criteria:
- Pregnant or lactating females
- Known human immunodeficiency virus (HIV) positive or acquired immune deficiency syndrome (AIDS) - related illness
- Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the protocol completion
- Total bilirubin > 1.5 × the upper limit of normal (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 × the ULN. AST, ALT may be elevated to 5 x the ULN if reasonably ascribed to underlying hematological disorder.
- Calculated creatinine clearance < 30 mL/minute
- Antineoplastic or radiotherapy within 14 days preceding the first dose
- Myocardial infarction within 6 months of enrollment or current history of New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
- Major surgery 14 days prior to the first dose
- Clinically uncontrolled central nervous system (CNS) involvement.
- Inability to swallow capsules
- History of uncontrolled sleep apnea or conditions that result in excessive daytime sleepiness, such as chronic lung disease
공부 계획
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연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Alisertib
Alisertib 50 mg, capsules, orally, twice daily for 7 days, followed by 14-day washout period, in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 26 Cycles).
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알리서팁 캡슐
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Best Overall Response Rate (ORR) Based on Investigator's Assessment
기간: Baseline and every 2 cycles up to Cycle 16 (up to Month 12), from Cycle 17 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Approximately 2.4 years)
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Best ORR is defined as the number of participants with complete remission(CR) or partial remission(PR) assessed by the Investigator using modified AML/MDS International Working Group(IWG) Criteria.
AML:CR=neutrophils >1x10^9/L, platelets >100x10^9/L, bone marrow blasts(BMB) <5%, transfusion independent, no extramedullary disease(EMD); CRi=BMB <5%, transfusion independent, no EMD; PR=neutrophils >1x10^9/L, platelets >100x10^9/L, BMB >50% decrease and 5% to 25%, blasts <5% with Auer rods; PRi=BMB >50% decrease and 5% to 25%.
MDS:CR=bone marrow: ≤5% myeloblasts with normal maturation, peripheral blood: hemoglobin ≥11 g/dL, platelets ≥100x10^9/L, neutrophils ≥1.0x10^9/L, blasts 0%; PR=all CR criteria if abnormal before treatment except: BMB decreased by ≥50% over pretreatment but still >5%; PRi=BMB decreased by ≥50% over pretreatment but still >5%; Marrow CR=bone marrow: ≤5% myeloblasts and decrease by ≥50% over pretreatment, peripheral blood hematologic improvement responses noted.
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Baseline and every 2 cycles up to Cycle 16 (up to Month 12), from Cycle 17 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Approximately 2.4 years)
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Progression Free Survival (PFS)
기간: Baseline and every 2 cycles up to Cycle 16 (up to Month 12), from Cycle 17 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Approximately 2.4 years)
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PFS is defined as the time from the date of first study drug administration to the date of first documented progressive disease (PD) or death.
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Baseline and every 2 cycles up to Cycle 16 (up to Month 12), from Cycle 17 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Approximately 2.4 years)
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Duration of Response (DOR)
기간: Baseline and every 2 cycles up to Cycle 16 (up to Month 12), from Cycle 17 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Approximately 2.4 years)
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Duration of response is defined as the time from the date of first documentation of a response to the date of first documented PD.
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Baseline and every 2 cycles up to Cycle 16 (up to Month 12), from Cycle 17 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Approximately 2.4 years)
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Best Overall Hematologic Improvement (HI) Response for Myelodysplastic Syndrome Based on Investigator Assessment
기간: Baseline and every 2 cycles up to Cycle 16 (up to Month 12), from Cycle 17 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Approximately 2.4 years)
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Best overall HI response is defined as percentage of participants with response as assessed by Investigator based on IWG criteria: 1)Erythroid response (pretreatment,<11 g/dL): hemoglobin (Hgb) increase by ≥1.5 g/dL, relevant reduction of units of red blood cell (RBC) transfusions by absolute number of at least 4 RBC transfusions/8 weeks compared to pretreatment transfusion number in previous 8 weeks.
Only RBC transfusions given for Hgb of ≤9.0 g/dL pretreatment will count in RBC transfusion response evaluation.
2)Platelet response (pretreatment,<100x10^9/L):Absolute increase of ≥30x10^9/L for participants starting->20x10^9/L platelets, increase <20x10^9/L to >20x10^9/L by at least 100%.
3)Neutrophil response (pretreatment,<1.0x10^9/L):At
least 100% increase and an absolute increase >0.5x10^9/L.
4)Progression or relapse after HI:At least 1 of following: 50% decrement from maximum response levels in granulocytes or platelets, or reduction in Hgb by ≥1.5 g/dL, or transfusion dependence.
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Baseline and every 2 cycles up to Cycle 16 (up to Month 12), from Cycle 17 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Approximately 2.4 years)
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Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths
기간: First dose of study drug to 30 days after last dose (Up to 18.9 months)
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An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment.
A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event.
Relationship of each AE to study drug was determined by the Investigator.
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First dose of study drug to 30 days after last dose (Up to 18.9 months)
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Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events
기간: First dose of study drug to 30 days after last dose (Up to 18.9 months)
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Vital signs measurements (blood pressure, heart rate, and oral temperature) were obtained throughout the study.
A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
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First dose of study drug to 30 days after last dose (Up to 18.9 months)
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Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events
기간: First dose of study drug to 30 days after last dose (Up to 18.9 months)
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Abnormal Laboratory Values for Chemistry or Hematology tests that were assessed by the investigator to be Grade 3 or higher using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).
Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death.
A treatment--emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
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First dose of study drug to 30 days after last dose (Up to 18.9 months)
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연구 주요 날짜
연구 시작 (실제)
2009년 2월 10일
기본 완료 (실제)
2010년 2월 2일
연구 완료 (실제)
2011년 7월 4일
연구 등록 날짜
최초 제출
2009년 1월 27일
QC 기준을 충족하는 최초 제출
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처음 게시됨 (추정)
2009년 1월 28일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2018년 5월 11일
QC 기준을 충족하는 마지막 업데이트 제출
2018년 4월 9일
마지막으로 확인됨
2018년 4월 1일
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