A Phase 3 Study of Siltuximab or Placebo in Combination With Velcade and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
2013年1月25日 更新者：Centocor, Inc.
A Phase 3, Randomized, Double-blind Study of Siltuximab (Anti-IL-6 Monoclonal Antibody) or Placebo in Combination With VELCADE and Dexamethasone for the Treatment of Subjects With Relapsed or Refractory Multiple Myeloma
The purpose of this study is to determine if there is an improvement in progression-free survival (length of time during and after treatment in which a patient is living with a disease that does not get worse) when siltuximab is added to VELCADE and dexamethasone in subjects with relapsed or refractory multiple myeloma.
調査の概要
状態
引きこもった
条件
詳細な説明
This is a research study with an experimental drug called siltuximab (also known as CNTO 328).
Siltuximab is being developed to see if it may be useful in treating multiple myeloma, including multiple myeloma that has returned after (relapsed) or did not respond (refractory) to previous treatment.
Multiple myeloma is a type of cancer that affects the blood and bone marrow.
The cancer cells in the bone marrow can cause the normal bone marrow cells to breakdown.
This can result in low levels of red blood cells (which may make the patient feel tired or fatigued), low levels of white blood cells (which may increase the patient's chances of infections) or low levels of platelets (which may increase risk of bleeding).
The cancer cells can cause damage to the normal bone.
This can cause bone pain, bone fractures, and can increase the level of calcium in the blood.
The cancer cells also make proteins (called M-proteins), which can result in damage to other organs, especially the kidneys.
Siltuximab is a chimeric (part mouse and part human) antibody (immunoglobulin that is important for fighting infection).
Siltuximab blocks another small protein called Interleukin 6 (IL-6).
The body makes IL-6 naturally, and at normal levels it is important for the inflammatory response.
But high levels of IL-6 can help cancer cells grow and interfere with chemotherapy drugs killing cancer cells.
Cancer-related sicknesses such as weight loss, bone weakening, and depression have been linked to high levels of IL-6.
This study tests the effectiveness and safety of siltuximab when it is taken together with Velcade and dexamethasone.
There are two treatment groups, Arm A and Arm B. To try to make sure the groups are similar, patients will be put into Arm A or Arm B, randomly (by chance), like flipping a coin.
Patients in Arm A will receive siltuximab plus Velcade and dexamethasone.
Patients in Arm B will receive placebo plus Velcade and dexamethasone.
About 500 patients will participate in the study.
Velcade, also known as bortezomib, is injected directly into the vein all at once.
This is called an intravenous (IV) push.
Siltuximab or placebo is given as a 1 hour IV infusion through a small tube that goes directly into the vein.
Dexamethasone is given orally.
The treatment period is divided into cycles lasting about 21 days which will last until the patient's multiple myeloma gets worse, side effects that are not acceptable happen or when the patient decides to withdraw consent for treatment, whichever occurs first.
Siltuximab 11mg/kg or placebo will be given on Day 1 of every cycle.
Velcade 1.3 mg/m2 will be given on Days 1, 4, 8 and 11 for Cycles 1-8, and on Days 1 and 8 for Cycles 9 and higher.
Dexamethasone 20 mg will be given on the day of and the day after each Velcade dose.
Safety assessments will be performed throughout the study and include obtaining and evaluating laboratory tests, vital signs (e.g.
blood pressure), and checking the occurrence and severity of adverse events.
Disease assessments will also be performed and include obtaining and evaluating blood and 24 hour urine samples, bone marrow aspirate and/or biopsy samples and clinical and radiologic evaluations.
After treatment, patients will enter the follow-up period, which includes visits up to 12 weeks after the last dose and checks every three months until death or the end of the study.
Patients who stop treatment before their multiple myeloma gets worse will have disease assessments until their disease gets worse, they start a new multiple myeloma treatment, they decide to withdraw consent for study participation or the end of the study, whichever happens first.
Siltuximab or placebo plus Velcade and dexamethasone will be given in 21-day treatment cycles until worsening of disease (progression), unacceptable toxicity or withdrawal of consent for treatment, whichever comes first.
Siltuximab 11 mg/kg or placebo will be given on Day 1 of every cycle.
Velcade 1.3 mg/m2 will be given on Days 1, 4, 8 and 11 for Cycles 1-8, and on Days 1 and 8 for Cycles 9 and higher.
Dexamethasone 20 mg will be given on the day of and the day after each Velcade dose.
研究の種類
介入
段階
- フェーズ 3
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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Iowa
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Iowa City、Iowa、アメリカ
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Massachusetts
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Boston、Massachusetts、アメリカ
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Ohio
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Toledo、Ohio、アメリカ
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Pennsylvania
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Willow Grove、Pennsylvania、アメリカ
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Wisconsin
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Milwaukee、Wisconsin、アメリカ
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Nottingham、イギリス
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Gandhinagar Guiarat、インド
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Cherkassy、ウクライナ
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Dnepropetrovsk、ウクライナ
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Kharkov、ウクライナ
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Khmelnitskiy、ウクライナ
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Kiev、ウクライナ
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Odessa、ウクライナ
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Simferopol、ウクライナ
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Vinnitsa、ウクライナ
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Apeldoorn、オランダ
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Deventer、オランダ
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Zwolle、オランダ
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Adelaide、オーストラリア
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Camperdown、オーストラリア
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Heidelberg、オーストラリア
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Parkville、オーストラリア
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Prahran、オーストラリア
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Toronto、カナダ
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Hradec Kralove、チェコ共和国
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Liberec、チェコ共和国
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Praha、チェコ共和国
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Praha 2、チェコ共和国
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Christchurch、ニュージーランド
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Grafton、ニュージーランド
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Nz 9 Takapuna Auckland、ニュージーランド
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Palmerston North、ニュージーランド
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Plovdiv N/A、ブルガリア
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Sofia、ブルガリア
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Varna、ブルガリア
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Edegem、ベルギー
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Liège、ベルギー
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Turnhout、ベルギー
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Yvoir、ベルギー
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Brzozow、ポーランド
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Gdansk、ポーランド
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Lodz、ポーランド
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Opole、ポーランド
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Wroclaw、ポーランド
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Ankara、七面鳥
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Bursa、七面鳥
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Edirne、七面鳥
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Hwasun Gun、大韓民国
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Seoul、大韓民国
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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:
- Confirmed diagnosis of multiple myeloma requiring treatment
- Measurable secretory disease, defined as either serum M-protein >=1 g/dL or urine M-protein (light chain) >=¿200 mg/24 hours
- Must have received 1 to 3 lines of prior treatment for multiple myeloma
- Must have achieved a response (Minimal Response or better) to at least 1 prior line of treatment
- Must have progressed on or been refractory (defined as < Minimal Response or disease progression within 60 days of last dose) to the most recent line of treatment
- Must not be refractory to any previous line of treatment that included a proteasome inhibitor
- Qualifying hematology and chemistry laboratory results.
Exclusion Criteria:
- Diagnosis of primary amyloidosis, plasma cell leukemia, or other conditions in which a paraprotein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
- Grade 1 peripheral neuropathy with pain or Grade 2 or higher peripheral neuropathy
- Allogeneic bone marrow transplantation within 28 days
- Bone marrow transplant planned within 12 months after study start
- Chemotherapy or radiation therapy within 21 days
- Clinically significant infection, including known HIV or hepatitis C infection, or known hepatitis B surface antigen positivity
- Major surgery within 21 days before or planned during the study
- Subjects who the investigator believes would not tolerate starting doses of VELCADE or dexamethasone
- Significant cardiac disease or myocardial infarction within 6 months
- Vaccination with live attenuated vaccines within 4 weeks
- Prior exposure to agents targeting IL-6 or the IL-6 receptor
- Received any investigational agent within 30 days¿
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：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
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：001
Siltuximab Velcade and dexamethasone Given in 21-day treatment cycles Siltuximab 11 mg/kg as 1 hour IV infusion on Day 1 of every cycle Velcade 1.3 mg/m2 IV push on Days 1 4 8 and 11 for Cycles 1-8 and on Days 1 and 8 for Cycles 9 and higher Dexamethasone 20 mg orally on the day of and the day after each Velcade dose
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Given in 21-day treatment cycles
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他の：002
Placebo Velcade and dexamethasone Given in 21-day treatment cycles Placebo as 1-hour IV infusion on Day 1 of every cycle Velcade 1.3 mg/m2 IV push on Days 1 4 8 and 11 for Cycles 1-8 and on Days 1 and 8 for Cycles 9 and higher Dexamethasone 20 mg orally on the day of and the day after each Velcade dose
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Siltuximab 11 mg/kg as 1 hour IV infusion on Day 1 of every cycle
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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 |
時間枠 |
|---|---|
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Progression-free survival (PFS)
時間枠：Event driven, i.e. every 3-4 weeks until progression, death, or end of study (5 years after first patient is dosed)
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Event driven, i.e. every 3-4 weeks until progression, death, or end of study (5 years after first patient is dosed)
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
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Overall survival
時間枠：Every 3 months until death or end of study (5 years after 1st patient is dosed)
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Every 3 months until death or end of study (5 years after 1st patient is dosed)
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Overall response rate
時間枠：Every 3 weeks until disease progression or end of study (5 years after 1st patient is dosed)
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Every 3 weeks until disease progression or end of study (5 years after 1st patient is dosed)
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Siltuximab pharmacokinetic evaluations (Cmin, Cmax) to provide information on the pharmacokinetic profile of siltuximab
時間枠：Day 1 of Cycles 1, 2, 3, 5, 7, 11, 15, and 19 and during the follow-up period (12 weeks after last dose)
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Day 1 of Cycles 1, 2, 3, 5, 7, 11, 15, and 19 and during the follow-up period (12 weeks after last dose)
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Dexamethasone pharmacokinetic evaluations (Cmin, AUC[t1-t2]) from approx. 30 patients from each treatment arm to provide information on the pharmacokinetic profile of dexamethasone
時間枠：Pre-dose on Day 1 of Cycles 1, 2 and 3; at Cycle 3 measured 1, 2, 4, 6 and 24 hours after dose
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Pre-dose on Day 1 of Cycles 1, 2 and 3; at Cycle 3 measured 1, 2, 4, 6 and 24 hours after dose
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Number of adverse events as a measure of safety and tolerability
時間枠：Routinely until 30 days after last dose at a minimum, or until end of study
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Routinely until 30 days after last dose at a minimum, or until end of study
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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。
スポンサー
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
2011年7月1日
一次修了 (予想される)
2014年4月1日
研究の完了 (予想される)
2014年12月1日
試験登録日
最初に提出
2010年12月23日
QC基準を満たした最初の提出物
2010年12月23日
最初の投稿 (見積もり)
2010年12月24日
学習記録の更新
投稿された最後の更新 (見積もり)
2013年1月28日
QC基準を満たした最後の更新が送信されました
2013年1月25日
最終確認日
2013年1月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- CR017743
- CNTO328MMY3001 (その他の識別子：Centocor, Inc.)
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。