Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
A Phase I Dose-Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) Following Cytoreduction With Chemotherapy
調査の概要
状態
条件
介入・治療
詳細な説明
PRIMARY OBJECTIVES:
I. Determine the toxicity profile, dose-limiting toxicity, and maximum tolerated dose of flavopiridol (alvocidib) as consolidation chemotherapy after cytoreduction chemotherapy in patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.
SECONDARY OBJECTIVES:
I. Determine the pharmacokinetics and cellular pharmacodynamics of flavopiridol in these patients.
II. Determine the complete response (CR) and overall response rate (CR and partial response) of patients treated with flavopiridol.
OUTLINE: This is a dose-escalation study. Patients receive alvocidib intravenously (IV) over 30 minutes (loading dose), followed by alvocidib IV over 4 hours on days 1, 8, and 15.
Treatment repeats every 5 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 12 patients are treated at the MTD (i.e., recommended phase II dose). Patients undergo blood collection at baseline and periodically during study for pharmacokinetic and cytokine studies (levels of tumor necrosis factor-alpha, interleukin [IL]-6, -11, and -16) by enzyme-linked immunosorbent assay (ELISA). Interphase cytogenetics, p53 mutational status, p53/ATM function, V_H mutational status, zeta-chain-associated protein kinase 70 (ZAP-70) overexpression, and single nucleotide polymorphisms are also examined.
After completion of study treatment, patients are followed at 2 months and then every 3 months for 5 years.
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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Ohio
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Columbus、Ohio、アメリカ、43210
- Ohio State University Medical Center
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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:
Diagnosis of 1 of the following:
- B-cell chronic lymphocytic leukemia (CLL)
- Small lymphocytic lymphoma (SLL)
Must have received 1-3 prior therapies for CLL
- Completed therapy 2-12 months ago
- Prior therapy must have led to a partial response or greater
- No evidence of progressive disease
- ECOG performance status 0-2
- Absolute neutrophil count ≥ 1,000/mm³
- WBC ≤ 5,000/mm³
- Platelet count ≥ 50,000/mm³
- Cytopenia allowed
- Creatinine < 2.0 mg/dL
- Bilirubin ≤ 1.5 times normal (unless due to Gilbert's disease or hemolysis)
- AST ≤ 2 times normal (unless due to hemolysis)
- No secondary malignancy or other disease that would limit survival to < 2 years
- No history of inflammatory bowel disease unless inactive for > 2 years
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- See Disease Characteristics
- No other concurrent chemotherapy
- No concurrent radiotherapy
- No concurrent dexamethasone or other corticosteroid-based antiemetics
- No concurrent chronic corticosteroid therapy
No other concurrent hormonal therapy except for the following:
- Steroids for new adrenal failure
- Hormones for nondisease-related conditions (e.g., insulin for diabetes)
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：Treatment (chemotherapy)
Patients receive alvocidib IV over 30 minutes (loading dose), followed by alvocidib IV over 4 hours on days 1, 8, and 15.
Treatment repeats every 5 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
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相関研究
与えられた IV
他の名前：
相関研究
他の名前：
|
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 |
|---|---|---|
|
Toxicity profile of alvocidib administered as a 30 minute loading dose followed by a 4-hour infusion once weekly for 3 consecutive weeks every 5 weeks as consolidation therapy following cytoreduction chemotherapy
時間枠：Day 1, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment
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Assessed utilizing the NCI Common Terminology Criteria for Adverse Events version 3.0.
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Day 1, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment
|
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Dose-limiting toxicity of alvocidib as consolidation chemotherapy after cytoreduction chemotherapy in patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma
時間枠：Course 1
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The National Cancer Institute Common Toxicity Criteria version 3.0 will be used to characterize toxicity.
If no patients experience dose-limiting toxicity, dose escalation will occur.
If 1 patient has a dose limiting toxicity, 3 additional patients will be enrolled at that dose.
If fewer than 2 of 6 patients experiences dose limiting toxicity, then the next highest dose level will be used for the subsequent cohort of 3 patients.
If at any dose level two or more of the six patients experience a dose limiting toxicity, 3 additional patients will be treated at the previous dose level.
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Course 1
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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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Pharmacokinetics and cellular pharmacodynamics of alvocidib administered in this schedule
時間枠：Baseline and day 1
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Cytokine studies will be examined by standard ELISA assays to determine if increase IL-6 correlates with hypotension, hypoxemia, and tachycardia observed following treatment and to identify the source of production of this cytokine.
We will examine interphase cytogenetics, p53 mutational status, p53/ATM functional assay, VH mutational status, and ZAP-70 over-expression.
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Baseline and day 1
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Complete response (CR) and overall response rate (CR and partial response) of alvocidib in patients with previously-treated CLL
時間枠：Baseline, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment
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Criteria for response will utilize the Revised National Cancer Institute-sponsored Working Group Guidelines.
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Baseline, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment
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協力者と研究者
捜査官
- 主任研究者：Leslie Andritsos、Ohio State University
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
一次修了 (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
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。
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