Oblimersen, Cytarabine, and Daunorubicin in Treating Older Patients With Acute Myeloid Leukemia
A Phase I Study of G3139 ( NSC # 683428) in Combination With Cytarabine and Daunorubicin in Previously Untreated Patients With Acute Myeloid Leukemia (AML)>= 60 Years of Age
調査の概要
状態
条件
詳細な説明
OBJECTIVES:
I. Determine the maximum tolerated dose of daunorubicin in combination with cytarabine and oblimersen in older patients with previously untreated acute myeloid leukemia.
II. Determine the qualitative and quantitative toxic effects of this regimen in these patients.
III. Determine the pharmacokinetics of oblimersen in this regimen in these patients.
IV. Determine the disease-free survival and overall survival of patients treated with this regimen.
V. Assess the spontaneous rate of apoptosis in leukemic blasts in patients before and after initiation of treatment with oblimersen.
VI. Determine therapeutic response (complete remission) in patients treated with this regimen.
OUTLINE: This is a dose-escalation study of daunorubicin. Patients are stratified according to disease status (primary vs secondary).
INDUCTION THERAPY: Patients receive oblimersen (G3139) IV continuously on days 1-10 and cytarabine IV continuously on days 4-10. Patients also receive daunorubicin IV daily on days 4-6.
Patients with bone marrow cellularity of at least 20% and at least 5% leukemic blasts at day 17 or evidence of refractory disease receive a second induction comprising G3139 IV continuously on days 1-8, cytarabine IV continuously on days 4-8, and daunorubicin IV on days 4-5.
CONSOLIDATION THERAPY: Beginning no sooner than 14 days after hematologic recovery from induction therapy, patients receive G3139 IV continuously on days 1-8 and cytarabine IV over 4 hours on days 4-8. Patients receive a second course of consolidation therapy no sooner than 14 days after hematologic recovery from the first course.
Cohorts of 3-6 patients receive escalating doses of daunorubicin 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.
Patients are followed every 2 months for 2 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:
Histologically confirmed primary or secondary acute myeloid leukemia (AML)
- More than 20% bone marrow blasts
- Myelodysplastic syndromes (MDS) or a chronic myeloproliferative disorder antecedent to AML allowed
- Therapy-related AML allowed
- No acute promyelocytic leukemia
- At least 4 weeks
- Bilirubin no greater than 2 mg/dL
- ALT and AST no greater than 2 times upper limit of normal (unless directly attributable to AML)
- Creatinine no greater than 2.5 mg/dL
- Ejection fraction at least 50% by MUGA or echocardiogram
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- No allergy to any of the study medications
- No other uncontrolled concurrent illness
- No serious medical or psychiatric illness that would preclude giving informed consent
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No prior therapy for primary AML except emergency leukapheresis
- No prior anthracyclines
- No prior chemotherapy for primary AML except hydroxyurea for hyperleukocytosis
- At least 3 months since prior chemotherapy for MDS or chronic myeloproliferative disorders antecedent to AML
- No other concurrent chemotherapy
- No concurrent corticosteroids as anti-emetics
- No concurrent steroids except for adrenal failure or septic shock
- No concurrent hormonal therapy except hormones for non-disease-related conditions (e.g., insulin for diabetes, tamoxifen or equivalent for breast cancer prevention or adjuvant treatment, or estrogens or progestins for gynecologic indications)
- No prior radiotherapy for primary AML except cranial radiotherapy for CNS leukostasis
- No concurrent palliative radiotherapy
- No concurrent whole brain radiotherapy
- No other concurrent investigational or commercial agents or therapies
- No concurrent cyclooxygenase-2 inhibitors
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：Arm I
INDUCTION THERAPY: Patients receive oblimersen (G3139) IV continuously on days 1-10 and cytarabine IV continuously on days 4-10. Patients also receive daunorubicin IV daily on days 4-6. Patients with bone marrow cellularity of at least 20% and at least 5% leukemic blasts at day 17 or evidence of refractory disease receive a second induction comprising G3139 IV continuously on days 1-8, cytarabine IV continuously on days 4-8, and daunorubicin IV on days 4-5. CONSOLIDATION THERAPY: Beginning no sooner than 14 days after hematologic recovery from induction therapy, patients receive G3139 IV continuously on days 1-8 and cytarabine IV over 4 hours on days 4-8. Patients receive a second course of consolidation therapy no sooner than 14 days after hematologic recovery from the first course. |
相関研究
与えられた IV
他の名前：
相関研究
他の名前：
与えられた IV
他の名前：
与えられた IV
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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MTD of cytarabine and daunorubicin in combination with G3139, defined as the dose level just below the dose level at which DLT is observed in 2 patients, graded according to NCI CTC version 2.0
時間枠：Up to day 10
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Up to day 10
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Incidence of adverse events, graded according to NCI CTC version 2.0
時間枠：Up to 2 years
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We will define the qualitative and quantitative toxicities in regard to organ specificity, time course, predictability, and reversibility.
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Up to 2 years
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
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全生存
時間枠：2年まで
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2年まで
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Pharmacokinetics of G3139
時間枠：During induction therapy on day 1 at hour 0 and 24hours after G3139 administration; day 4 at hour 73 before cytarabine administration; day 11 at hour 0 and .5, 1, 2, 4, 6, and 8 hours
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During induction therapy on day 1 at hour 0 and 24hours after G3139 administration; day 4 at hour 73 before cytarabine administration; day 11 at hour 0 and .5, 1, 2, 4, 6, and 8 hours
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Level of bcl-2 in circulating and/or marrow leukemic blasts before and after initiation of treatment with G3139
時間枠：Up to 18 weeks
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Up to 18 weeks
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Spontaneous rate of apoptosis in leukemic blasts before and after initiation of treatment with G3139
時間枠：Up to 18 weeks
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Up to 18 weeks
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Incidence of therapeutic response (complete remission [CR])
時間枠：Up to 2 years
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Up to 2 years
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無病生存
時間枠：2年まで
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2年まで
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協力者と研究者
捜査官
- 主任研究者：Guido Marcucci、Ohio State University
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
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
- NCI-2012-01409
- U01CA076576 (米国 NIH グラント/契約)
- OSU-0164
- NCI-4630
- CDR0000069353
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