Activity & Safety Study of Lenalidomide & Rituximab as Non-chemotherapy Based Therapy on Chronic Lymphocytic Leukemia (LLC-LENAR-08)
Phase I Study of the Activity and Safety of Lenalidomide and Rituximab as Non-chemotherapy Therapy for Patients With Recurrent and Refractory Chronic Lymphocytic Leukemia
The rationale for combining lenalidomide with rituximab derives from preclinical observations suggesting that lenalidomide may enhance the ADCC (antigen-dependent cellular cytotoxicity) triggered by monoclonal antibodies such as rituximab. Lenalidomide augments NK cytotoxicity by increasing CD56dimCD3 subset, in addition to inducing IL-2 in T cells. These results provide the cellular and molecular basis for the use of lenalidomide as an adjuvant in immunotherapeutic strategies of monoclonal antibodies (mAb)-based therapies. The combination lenalidomide-rituximab was tested in lymphoma cell lines but not specifically on CLL cell lines. However the observed synergism was attributed to NK cells expansion, thus lending support to the notion that this synergism may operate in other B-cell lymphoproliferative malignancies.
The objective was to develop a non-cytotoxic and effective treatment for CLL that would fulfill an unmet medical need, as a significant proportion of CLL patients are elderly and frail. These patients experience an excess in chemotherapy induced toxicity, often preventing the completion of the planned treatment.
調査の概要
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
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Córdoba、スペイン、14004
- Hospital Universitario Reina Sofia
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Madrid、スペイン、28046
- Hospital Universitario La Paz
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Madrid、スペイン、28033
- MD Anderson Internacional España
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Salamanca、スペイン、37007
- Hospital Clínico de Salamanca
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Sevilla、スペイン、41013
- Hospital Virgen Del Rocio
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Valencia、スペイン、46010
- Hospital Clínico Universitario de Valencia
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Zaragoza、スペイン、50009
- Hospital Universitario Miguel Servet
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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:
- Recurrent and refractory CLL patients that have received at least one previous treatment with purine analogs.
- Adequate liver function and renal function.
- ECOG performance status ≤ 2.
- Signed informed consent
- Male and female patients who are fertile agree to use an effective barrier method of birth control to avoid pregnancy.
Exclusion Criteria:
- Positive serological markers for hepatitis B with the exception of HBsAc in previously vaccinated patients
- Pregnant patients
- HIV infection
- Concurrent chemotherapy or immunotherapy
- Other malignancy within the last 2 years, except for localized cutaneous carcinoma
- Neurological impairment precluding understanding of protocol and the entailed visits and procedures.
- Patients with Renal insufficiency that requires dialysis.
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：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：Lenalidomida, Rituximab
Phase I: Lenalidomide will be administered from day 1 to 21 of 28 days cycles, escalating doses (from 2,5mg to 25 mg).Rituximab dose will be administered at the standard (375 mg/m2 in the first cycle and 500 mg/m2 in successive cycles).
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Lenalidomide: Oral use. It will be administered from day 1 to 21 of 28 days cycles in a total of 6 cycles. Rituximab, intravenous use. The dose will be administered at the standard (375 mg/m2 in the first cycle and 500 mg/m2 in successive cycles). In the first cycle Rituximab will be administered in two divided doses:100mg/m2 total on day 1 and the rest up to 375mg/m2 on day 2. If lenalidomide treatment starts on day 1, Rituximab will be administered, in this first cycle, on days -2 (100 mg/m2) and -1 (275 mg/m2). In the second and subsequent cycles, 500 mg/m2 of Rituximab will be administered on day -1.
他の名前：
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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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Phase I: To determine Starting Recommended Dose for the first cycle and the subsequent cycles (Maximal Tolerated Dose)in relapsed B-cell CLL patients.
時間枠：5 months
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6 treatment cycles followed by an evaluation visit (between 60-90 days after last dosing) and quarterly follow up visits, until disease progression.
Module I: patients on every cohort will have the same dose during treatment, except if they experiment DLT, in which case dose will be decreased (unless they are on the first dose level).
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5 months
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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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To determine the toxicity profile of LenRtx.
時間枠：5 months
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Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
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5 months
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To determine the time to treatment failure.
時間枠：5 months
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Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
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5 months
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To determine the molecular response rate.
時間枠：5 months
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Phase II: patients will be followed during 6 cycles, safety assessment visit and quarterly follow up visits
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5 months
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To determine the clinical response rate (combined morphological and flow cytometry criteria).
時間枠：5 months
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6 treatment cycles followed by an evaluation visit (between 60-90 days after last dosing) and quarterly follow up visits, until disease progression
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5 months
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協力者と研究者
捜査官
- 主任研究者：José F Tomas, MD、MD Anderson Internacional España
研究記録日
主要日程の研究
研究開始
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 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
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
追加の関連 MeSH 用語
その他の研究ID番号
- LLC-LENAR-08 (その他の識別子：Fundación MD Anderson Internacional. España)
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