高用量治療に不適格な未治療の多発性骨髄腫患者を対象に、レナリドミドおよび皮下投与のダラツムマブとレナリドミドおよびデキサメタゾンの比較 (IFM2017_03)
高用量治療に不適格な未治療の多発性骨髄腫患者を対象に、レナリドミドと皮下投与のダラツムマブ（R-Dara SC）とレナリドミドとデキサメタゾン（Rd）を比較する第 III 相試験
This is a Phase 3, randomized (study drug assigned by chance), open-label (participants and researchers are aware about the treatment, participants are receiving), active-controlled (study in which the experimental treatment or procedure is compared to a standard treatment or procedure), parallel-group (each group of participants will be treated at the same time), and multicenter (when more than one hospital team work on a medical research study) study in participants with newly diagnosed multiple myeloma (a blood cancer of plasma cells) and who are not candidates for high dose chemotherapy (treatment of disease, usually cancer, by chemical agents) and autologous stem cell transplant (ASCT). The primary hypothesis of this study is that subcutaneous Daratumumab in combination with Lenalidomide will prolong progression-free survival and likely induce less toxicity as compared with Lenalidomide and dexamethasone, in elderly frail subjects with newly diagnosed Multiple myeloma who are ineligible for high dose chemotherapy and ASCT
調査の概要
状態
条件
詳細な説明
The primary hypothesis of this study is that subcutaneous Daratumumab in combination with Lenalidomide will prolong progression-free survival and likely induce less toxicity as compared with Lenalidomide and dexamethasone, in elderly frail subjects with newly diagnosed Multiple myeloma who are ineligible for high dose chemotherapy and ASCT
研究の種類
入学 (実際)
段階
- フェーズ 3
連絡先と場所
研究場所
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-
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Besançon、フランス
- Chru Jean Minjoz
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Blois、フランス
- Ch Blois Simone Veil
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Bourg-en-Bresse、フランス
- Ch Fleyriat
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Brest、フランス
- Chru Brest Site Hopital Morvan
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Caen、フランス
- Chu de Caen Normandie
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Cesson-Sévigné、フランス
- Hopital Prive Sevigne - Cesson
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Dijon、フランス
- Chu Dijon Bourgogne
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Grenoble、フランス
- Chu de Grenoble
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La Rochelle、フランス
- Gpe Hospitalier La Rochelle-Re-Aunis
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Le Coudray、フランス
- Ch Chartres Louis Pasteur-Le Coudray
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Lille、フランス
- Hôpital Claude Huriez, CHU
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Marseille、フランス
- Institut Paoli Calmettes
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Mont-de-Marsan、フランス
- Chi Mont de Marsan Et Pays Des Sources
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Montpellier、フランス
- Chu Montpellier
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Nantes、フランス
- Chu de Nantes Site Hotel Dieu Hme
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Nice、フランス
- Chu de Nice Hopital de L'Archet
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Pessac、フランス、33604
- Hopital Haut-Leveque - Chu
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Périgueux、フランス
- Centre Hospitalier de Perigueux
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Rennes、フランス
- Chru Rennes Site Pontchaillou
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Saint-Quentin、フランス
- Centre Hospitalier de Saint Quentin
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St-Malo、フランス
- Centre Hospitalier Saint-Malo
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Toulouse、フランス
- Oncopole Chu Toulouse
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Tours、フランス
- Chu de Tours
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
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Subject must be at least 65 years of age.
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Subject must have documented multiple myeloma satisfying the CRAB criteria and measurable disease.
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Newly diagnosed and not considered candidate for high-dose chemotherapy with SCT.
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Subject must have a Frailty Score ≥ 2
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Subject must have within 5 days prior to first drug intake (C1D1) pretreatment clinical laboratory values meeting the following criteria during the Screening Phase:
- hemoglobin ≥7.5 g/dL
- absolute neutrophil count ≥1.0 x 109/L
- platelet count ≥70 x 109/L
- aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN)
- alanine aminotransferase (ALT) ≤2.5 x ULN
- total bilirubin ≤2.0 x ULN
- creatinine clearance≥30mL/min
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Measurable ISS with β2-microglobulin and albumin values for randomization
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A man who is sexually active with a woman of childbearing potential must agree to use a latex or synthetic condom, even if they had a successful vasectomy. All men must also not donate sperm during the study, for 4 weeks after the last dose of lenalidomide, and for 4 months after the last dose of daratumumab. Women participating in this study must be postmenopausal.
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Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study. Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol, as referenced in the ICF.
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Subjects affiliated with an appropriate social security system.
Exclusion Criteria:
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Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma.
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Subject has a diagnosis of Waldenström's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
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Subject has prior or current systemic therapy or SCT for multiple myeloma
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Subject has a history of malignancy (other than multiple myeloma) within 5 years before the date of randomization
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Subject has had radiation therapy within 14 days of randomization.
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Subject has had plasmapheresis within 28 days of randomization.
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Subject is exhibiting clinical signs of meningeal involvement of multiple myeloma.
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Subject has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume [FEV] in 1 second <60% of predicted normal), persistent asthma, or a history of asthma within the last 2 years (intermittent asthma is allowed).
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Subject is known to be seropositive for history of human immunodeficiency virus (HIV)
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Seropositive for hepatitis B.
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(Known to be) seropositive for hepatitis C
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Subject has any concurrent medical or psychiatric condition or disease that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study.
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Subject has clinically significant cardiac disease, including:
- myocardial infarction within 1 year before randomization, or an unstable or uncontrolled disease/condition related to or affecting cardiac function
- uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities
- screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470 msec
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Subject has known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients
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Subject has plasma cell leukemia or POEMS syndrome
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Subject is known or suspected of not being able to comply with the study protocol. Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject or that could prevent, limit, or confound the protocol-specified assessments.
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Subject has had major surgery within 2 weeks before randomization or has not fully recovered from surgery.
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Subject has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks before randomization or is currently enrolled in an interventional investigational study.
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Refusal to consent or protected by legal regime ( guardianship, trusteeship)
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Subject has contraindications to required prophylaxis for deep vein thrombosis and pulmonary embolism
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Incidence of gastrointestinal disease that may significantly alter the absorption of oral drugs.
研究計画
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：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 |
|---|---|
|
実験的：Arm 1: Experimental group
Daratumumab SC 1800 mg
|
Daratumumab SC 1800 mg
Lenalidomide PO (25mg): days 1 through 21 of each 28-day cycle, until progression Dexamethasone PO (20mg): days 1, 8, 15, 22 of each 28-day cycle, until progression |
|
偽コンパレータ：Arm 2: Control group
Lenalidomide PO (25mg): days 1 through 21 of each 28-day cycle, until progression Dexamethasone PO (20mg): days 1, 8, 15, 22 of each 28-day cycle, until progression |
Lenalidomide PO (25mg): days 1 through 21 of each 28-day cycle, until progression Dexamethasone PO (20mg): days 1, 8, 15, 22 of each 28-day cycle, until progression |
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 |
|---|---|---|
|
Comparison of the efficacy of Daratumumab SC injection when combined with Lenalidomide (R-Dara SC) vs Lenalidomide and Dexamethasone (Rd): PFS
時間枠：From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
|
The primary objective is to compare the efficacy of Daratumumab SC injection when combined with Lenalidomide (R-Dara SC) to that of Lenalidomide and Dexamethasone (Rd), in terms of PFS in frail subjects with newly diagnosed myeloma who are not candidates for high dose chemotherapy and autologous stem cell transplant. |
From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
治療失敗までの時間
時間枠：無作為化日から、最初に記録された進行日または毒性日または何らかの原因による死亡日のいずれか早い方まで、最大84か月まで評価
|
無作為化日から、最初に記録された進行日または毒性日または何らかの原因による死亡日のいずれか早い方まで、最大84か月まで評価
|
|
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次の治療までの時間
時間枠：無作為化日から、最初に記録された進行日または毒性日または何らかの原因による死亡日のうち、いずれか早い方まで、最大84か月まで評価
|
無作為化日から、最初に記録された進行日または毒性日または何らかの原因による死亡日のうち、いずれか早い方まで、最大84か月まで評価
|
|
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PFS2 時間
時間枠：無作為化日から、最初に記録された進行日または毒性日または何らかの原因による死亡日のうち、いずれか早い方まで、最大84か月まで評価
|
無作為化日から、最初に記録された進行日または毒性日または何らかの原因による死亡日のうち、いずれか早い方まで、最大84か月まで評価
|
|
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イベントフリーサバイバル
時間枠：無作為化日から、最初に記録された進行日または毒性日または何らかの原因による死亡日のうち、いずれか早い方まで、最大84か月まで評価
|
無作為化日から、最初に記録された進行日または毒性日または何らかの原因による死亡日のうち、いずれか早い方まで、最大84か月まで評価
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Overall survival (OS) time
時間枠：From date of randomization until the date of death from any cause, whichever came first, assessed up to 84months
|
Overall survival (OS) time, |
From date of randomization until the date of death from any cause, whichever came first, assessed up to 84months
|
|
Complete remission (CR)
時間枠：From date of randomization until the date of first documented progression whichever came first, assessed up to 84months
|
Percentage of participants with CR, as defined by the IMWG criteria, will be reported. |
From date of randomization until the date of first documented progression whichever came first, assessed up to 84months
|
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Very good partial response (VGPR) or better.
時間枠：From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
|
VGPR or better, defined as VGPR or CR according to the IMWG criteria during or after the study treatment at the time of data cutoff. |
From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
|
|
Overall response (CR + VGPR + partial response [PR]).
時間枠：From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
|
Overall response, defined as CR or VGPR or PR, according to the IMWG criteria |
From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
|
|
Occurrence of grade 3 or more side effects.
時間枠：From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
|
Collecting all AE (grade 3 or more) |
From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
|
|
Safety and tolerability of Daratumumab SC when administered in combination with Revlimid: NCI-CTCAE V5.0.
時間枠：From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
|
Evaluation of safety data by type, frequency, severity, relation to study drug, according to NCI-CTCAE V5.0. |
From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
|
|
Evaluation of quality of life based on MY20 questionnaires
時間枠：From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
|
Treatment effects on patient reported outcomes and heath economic/resource utilization. |
From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
|
|
Evaluation of quality of life based on EORTC C30 questionnaires
時間枠：From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
|
Treatment effects on patient reported outcomes and heath economic/resource utilization. |
From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
|
|
Evaluation of quality of life based on EQ-5D questionnaires
時間枠：From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
|
Treatment effects on patient reported outcomes and heath economic/resource utilization. |
From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months
|
|
Minimal residual disease (MRD) negative rate at 12 months.
時間枠：after 12 months of treatment
|
Proportion of participants assessed as MRD negative |
after 12 months of treatment
|
協力者と研究者
捜査官
- 主任研究者：Thierry Facon, MD,PhD、University Hospital, Lille
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 2018_16
- 2018 (米国 NIH グラント/契約)
- 2018-003535-30 (EudraCT番号)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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