A Study of IXAZOMIB in Adult Patients With Lymphoma
2015年10月12日 更新者：Millennium Pharmaceuticals, Inc.
An Open-Label, Dose-Escalation, Phase 1 Study of IXAZOMIB (MLN9708), A Second-Generation Proteasome Inhibitor, in Adult Patients With Lymphoma
This study is an open-label, multicenter, phase 1, dose-escalation study of IXAZOMIB in adult patients with lymphoma.
This study will be the first to administer IXAZOMIB to patients with lymphoma.
調査の概要
研究の種類
介入
入学 (実際)
31
段階
- フェーズ 1
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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California
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Beverly Hills、California、アメリカ、90211
- Tower Cancer Research Center
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Colorado
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Denver、Colorado、アメリカ、80218
- Rocky Mountain Cancer Center
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Kansas
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Westwood、Kansas、アメリカ、66160
- Kansas University Medical Center
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New York
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New York City、New York、アメリカ、10021
- Cornell University
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ、19107
- Thomas Jefferson University
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Wisconsin
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Madison、Wisconsin、アメリカ、53792
- University of Wisconsin Madison
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Quebec
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Montreal、Quebec、カナダ、H3T 1E2
- Jewish General Hospital
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- Male or female patients 18 years or older.
- Eastern Cooperative Oncology Group performance status 0-2.
- Patients must have a confirmed diagnosis of lymphoma that is relapsed and/or refractory after at least 2 prior chemotherapeutic regimens and for which no curative option exists. Patients with Waldenstrom's macroglobulinemia are not eligible for enrollment in this study. Patients with Hodgkin lymphoma are considered eligible for this study.
- Suitable venous access for PK and pharmacodynamic evaluations.
Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
Male patients who agree to to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
- Voluntary written consent must be obtained.
Adequate blood and chemistry values during the screening period:
- Absolute neutrophil count (ANC) ≥ 1,500/mm3; platelet count ≥ 100,000/mm3.
- Total bilirubin must be ≤ 1.5 × the upper limit of the normal range upper limit of normal (ULN).
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be ≤ 2.5 × the upper limit of normal (ULN). AST and ALT may be elevated up to 5 times the upper limit of normal if their elevation can be reasonably ascribed to the presence of metastatic disease.
- Calculated creatinine clearance ≥ 30 mL/minute.
Exclusion Criteria:
- Peripheral neuropathy ≥ Grade 2.
- Female patients who are lactating or have a positive serum pregnancy test during the screening period .
- Major surgery within 14 days before the first dose of treatment.
- Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study treatment.
- Life-threatening illness unrelated to cancer.
- Diarrhea > Grade 1 based on the NCI CTCAE categorization.
- Systemic antineoplastic therapy/or radiotherapy within 21 days before the first dose of study treatment.
- Systemic treatment with prohibited medications.
- Patient has symptomatic brain metastases.
- Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or myocardial infarction within the past 6 months.
- QTc > 470 milliseconds (msec) on a 12-lead electrocardiogram (ECG) obtained during the screening period.
- Known human immunodeficiency virus (HIV), hepatitis B or hepatitis C positive.
- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
- Treatment with any investigational products within 28 days before the first dose of study treatment.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：IXAZOMIB
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Patients will be administered IXAZOMIB by IV on Days 1, 8, and 15 of a 28-day cycle.
The first stage of the study will be initiated at a starting dose of 0.125 mg/m2.
Subsequent doses will increase until a maximum tolerated dose (MTD) is established.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
時間枠：Baseline up to 30 days after last dose of study drug
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An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.
An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.
A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event.
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Baseline up to 30 days after last dose of study drug
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Number of Participants Reporting at Least 1 TEAE Related to Laboratory Assessments
時間枠：Baseline and Days 1, 8, and 15 of each treatment cycle (up to Cycle 45)
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The number of participants with any markedly abnormal standard safety laboratory values collected throughout study.
Hematology, clinical chemistry and urinalysis were performed.
TEAEs related to laboratory assessment observed at any time-points were reported under 3 system organ classes: blood and lymphatic system disorders, metabolism and nutrition disorders, and investigations.
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Baseline and Days 1, 8, and 15 of each treatment cycle (up to Cycle 45)
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Number of Participants With Clinically Significant Change From Baseline in Vital Signs
時間枠：Baseline and Days 1, 8, 15 of each treatment cycle up to 45 treatment cycles
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Vital signs included body temperature, weight, systolic and diastolic blood pressure and heart rate.
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Baseline and Days 1, 8, 15 of each treatment cycle up to 45 treatment cycles
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Maximum Tolerated Dose (MTD)
時間枠：Treatment Cycle 1
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The MTD was defined as the highest dose of ixazomib that generated dose limiting toxicity (DLT) during Cycle 1 in 0 of 3 or 1 of 6 participants.
DLT defined as any of the following considered possibly related to therapy by investigator: Grade 4 neutropenia (absolute neutrophil count [ANC] <500 cell per cubic millimeter [cells/mm^3]) for >7 days; Grade 3 neutropenia with fever or infection; Grade 4 thrombocytopenia for >7 days; platelet count <25,000 cells/mm^3; Grade 3 thrombocytopenia with clinically significant bleeding; platelet count <10,000/mm^3; Grade 2 peripheral neuropathy with pain or Grade 3 peripheral neuropathy; >=Grade 3 nausea/emesis, diarrhea controlled by maximal supportive therapy; Grade 3 QTc prolongation>500 millisecond (msec);any >=Grade 3 nonhematologic toxicity except arthralgia/myalgia; <1 week fatigue; delay in the initiation of the subsequent therapy cycle by >=7 days ; other Grade 2 ixazomib-related nonhematologic toxicities requiring therapy discontinuation.
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Treatment Cycle 1
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Recommended Phase 2 Dose (RP2D)
時間枠：Baseline up to Treatment Cycle 45
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The RP2D of Ixazomib was determined in Part 1 (dose escalation) on the basis of the totality of safety, tolerability, pharmacokinetics (PK), pharmacodynamic and preliminary efficacy data observed in Cycles 1 and 2 and beyond.
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Baseline up to Treatment Cycle 45
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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C0: Initial Plasma Concentration After Bolus Intravenous Administration
時間枠：Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 336 hours postdose)
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C0 is the plasma drug concentration at time zero following bolus intravenous injection, obtained from the plasma concentration-time curve.
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Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 336 hours postdose)
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AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib
時間枠：Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
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AUC(0-168) is a measure of the area under the plasma concentration time-curve from time 0 to 168 hours postdose
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Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
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Terminal Phase Elimination Half-life (T1/2) for Ixazomib
時間枠：Cycle 1 Day 15: Predose and at multiple time points (up to 336 hours postdose)
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Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
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Cycle 1 Day 15: Predose and at multiple time points (up to 336 hours postdose)
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Rac: Accumulation Ratio for Ixazomib
時間枠：Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
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Rac was estimated as the ratio of AUC (0-168) on Day 15 and AUC (0-168) on Day 1. AUC (0-168) is the area under the plasma concentration-time curve from time 0 to 168 hours postdose.
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Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
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Ae (0-4): Amount of Drug Excreted in Urine From 0 to 4 Hours Postdose
時間枠：Cycle 1, Days 1 and 15: 0 to 4 hours postdose
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Ae (0-4) is the total amount of drug excreted in the urine from 0 to 4 hours postdose.
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Cycle 1, Days 1 and 15: 0 to 4 hours postdose
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Fe (0-4): Fraction of Dose Excreted Unchanged in Urine From 0 to 4 Hours Postdose
時間枠：Cycle 1, Days 1 and 15: 0 to 4 hours postdose
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Fe (0-4) is the fraction of the dose excreted unchanged in the urine from 0 to 4 hours postdose, calculated as percentage of the exact dose administered.
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Cycle 1, Days 1 and 15: 0 to 4 hours postdose
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CLr: Renal Clearance
時間枠：Cycle 1, Days 1 and 15: 0 to 4 hours postdose
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CLr is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time, calculated as the amount of drug excreted in the urine divided by the area under the plasma concentration-time curve, expressed in liter per hour (L/hr).
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Cycle 1, Days 1 and 15: 0 to 4 hours postdose
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Emax: Maximum Observed Effect for Ixazomib
時間枠：Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
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Emax is the maximum inhibition of 20S proteasome activity in whole blood.
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Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
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TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib
時間枠：Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
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TEmax: Time to reach the maximum observed effect (Emax), equal to time (hours) to Emax.
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Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
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Overall Best Response
時間枠：Baseline up to Cycle 45
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Overall best response is the best response observed for a participant during the study based on International Working Group (IWG) Response Criteria for malignant lymphoma.
Complete response (CR) as per IWG is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.
Partial response (PR) is a minimum of 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses and no increase in the size of other nodes.
Stable disease (SD) is when a participant fails to attain the criteria needed for a CR or PR, but does not fulfill those for PD.
PD is any new lesion or increase by >50% of previously involved sites from nadir.
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Baseline up to Cycle 45
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2009年8月1日
一次修了 (実際)
2014年10月1日
研究の完了 (実際)
2014年10月1日
試験登録日
最初に提出
2009年5月4日
QC基準を満たした最初の提出物
2009年5月5日
最初の投稿 (見積もり)
2009年5月6日
学習記録の更新
投稿された最後の更新 (見積もり)
2015年11月11日
QC基準を満たした最後の更新が送信されました
2015年10月12日
最終確認日
2015年10月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。