Study of Vosaroxin and Decitabine in Older Patients With Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome
A Phase I/II Study of Vosaroxin and Decitabine in Older Patients With Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome
調査の概要
詳細な説明
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 4 groups of up to 6 participants will be enrolled in the Phase I portion of the study, and up to 60 participants will be enrolled in Phase II.
If you are enrolled in the Phase I portion, the dose of vosaroxin you receive will depend on when you joined this study. The first group of participants will receive the highest dose level of vosaroxin. If no intolerable side effects are seen, the study will move on to Phase II. If intolerable side effects are seen, each new group will receive a lower dose of vosaroxin than the group before it until the most tolerable dose is found.
If you are enrolled in the Phase II portion, you will receive vosaroxin at the highest dose that was tolerated in the Phase I portion.
All participants will receive the same dose level of decitabine.
Study Drug Administration:
You will receive the study drugs in cycles. The study cycles will be 4-12 weeks long, depending on if/how the disease responds to the treatment, how your bone marrow reacts to treatment, and what the doctor thinks is in your best interest.
On Days 1-5 of each study cycle, you will receive decitabine by vein over about 1 hour. On Days 1 and 4 of each cycle, you will also receive vosaroxin by vein over 8-10 minutes, before you receive decitabine. Depending on how the disease responds to the study drugs, the number of days you receive the study drug may change. Your doctor will discuss this with you.
The first 2 cycles are called Induction Cycles. All cycles after that are called Consolidation Cycles. All participants will receive Induction Cycle 1. If the study doctor thinks it is needed, you will also receive Induction Cycle 2. If after that the study doctor thinks it is in your best interest, you will receive up to 5 Consolidation Cycles of treatment.
Study Visits:
On Day 1 of each cycle, you will have a physical exam.
Every week, blood (about 1 tablespoon) will be drawn for routine tests. If at any point you appear to have a response to the study drugs, this blood will then be drawn every 1-2 weeks while you are still receiving the study drugs. If your doctor thinks it is needed, more blood may need to be drawn.
On Day 21 of Cycle 1 (+/- 7 days), then every 4 weeks after that, you will have a bone marrow aspiration and/or biopsy to check the status of the disease. If the doctor thinks it is needed, these may be done more or less often, depending on your response to the study drugs.
Length of Study:
You may receive the study drugs for up to 7 cycles. You will be taken off study if the disease gets worse, intolerable side effects occur, or if the study doctor thinks it is in your best interest.
Your participation in the study will be over after the follow-up period.
End-of-Study Visit:
If you are taken off study or if you leave the study early, you will have an end-of-study visit. At this visit:
Blood (about 2-3 teaspoons) will be drawn for routine tests. If the study doctor thinks it is needed, you will have a bone marrow aspiration.
You will then be contacted during a study visit or called and asked about any side effects you may be having 30 days after the end-of-study visit. This call will last about 5 minutes.
Follow-up:
If you do not leave the study early, you will have follow-up visits and calls for up to 5 years after you stop receiving the study drugs.
Every 4-8 weeks, blood (about 1 tablespoon) will be drawn for routine tests. If you cannot return to the clinic, you may have blood drawn at a clinic close to your home.
Every 3-6 months, you will be contacted during a clinic visit and asked how you are doing. If you cannot make it to the clinic for this visit, you will be called. The phone call should last about 5 minutes.
This is an investigational study. Vosaroxin is not FDA approved or commercially available. It is currently being used for research purposes only. Decitabine has been approved by the FDA for the treatment of MDS, which is a precursor of AML, but has not been approved for the treatment of AML. The use of these drugs in combination is investigational. The study doctor can explain how the drugs are designed to work.
Up to 84 patients will take part in this study. All will be enrolled at MD Anderson.
研究の種類
入学 (実際)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究場所
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Texas
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Houston、Texas、アメリカ、77030
- University of Texas MD Anderson Cancer 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:
- Previously untreated AML (>/= 20% blasts). Patients with high-risk MDS (defined as having >/= 10% blasts in the bone marrow) or patients with Chronic Myelomonocytic Leukemia (CMML) (having >/= 10% blasts in the bone marrow) may also be eligible after discussion with Principal Investigator (PI). Prior therapy with hydroxyurea, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is allowed, however prior therapy with chemotherapy agents for the disease under study is not allowed. Patients may have received one dose of cytarabine (up to 2 g/m2) administered at presentation for control of hyperleucocytosis. For patients with prior MDS or CMML who transformed to AML, therapy received for MDS is not considered as prior therapy for AML.
- Age >/= 60 years and not candidates for conventional cytotoxic chemotherapy or refuse it; OR patients below the age of 60 years who are considered unfit and/or unable to tolerate standard chemotherapy at the discretion of the treating physician or the principal investigator. "
- Eastern Cooperative Oncology Group performance status </= 2.
- Adequate hepatic (serum total bilirubin </= 1.5 x upper limit normal (ULN), alanine aminotransferase and/or aspartate transaminase </= 2.5 x ULN) and renal function (creatinine </= 2.0 mg/dL).
- Left ventricular ejection fraction (LVEF) at least 40% by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO)
- Patients must be willing and able to review, understand, and provide written consent before starting therapy.
- Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum pregnancy test within 14 days before the start of the treatment. Women of childbearing potential may have a urine pregnancy test, instead of a serum pregnancy test. If either the serum or urine pregnancy test is equivocally negative the patient will be eligible for the protocol. Women of childbearing potential must agree to use an adequate method of contraception during the study until 30 days after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 30 days after the last treatment.
Exclusion Criteria:
- New York Heart Association class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as active angina pectoris, clinically significant cardiac arrhythmia that requires therapy in the opinion of the treating physician or PI, uncontrolled hypertension (blood pressure > 160 systolic and > 110 diastolic not responsive to antihypertensive medication), uncontrolled diabetes mellitus in the opinion of the treating physician or PI, or uncontrolled congestive heart failure in the opinion of the treating physician or PI.
- Myocardial infarction in the previous 12 weeks (from the start of treatment).
- Active and uncontrolled disease/infection as judged by the treating physician
- Pregnant or breastfeeding
- Known Human Immunodeficiency Virus seropositivity
- Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator or medical monitor
- Acute promyelocytic leukemia (APL).
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：Vosaroxin + Decitabine
The first 6 patients on study (first cohort) receive 1 or 2 induction cycles of therapy according to the following starting schedule: Vosaroxin administered intravenously on days 1 and 4 at a dose of 90 mg/m2 in the first cycle (induction 1) for a total dose of 180 mg/m2/cycle in combination with Decitabine at a dose of 20 mg/m2 intravenously daily for 5 consecutive days (Days 1 to 5). Following the phase I portion, patients in phase II receive the following induction:
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Phase I Starting Dose: 90 mg/m2 by vein on Days 1 and 4 of each cycle. Phase II Starting Dose: 70 mg/m2 by vein on Days 1 and 4 of each cycle, or maximum tolerated dose from Phase I.
Phase I and II: 20 mg/m2 by vein daily for 5 consecutive days (Days 1 to 5).
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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Maximum Tolerated Dose (MTD) of Vosaroxin in Combination With Decitabine
時間枠：21 days
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Maximum tolerated dose (MTD) defined as highest daily oral dose evaluated at which <33% of patients experience a dose limiting toxicity (DLT).
A non-hematologic dose-limiting toxicity (DLT) defined as a clinically significant grade 3 or 4 adverse event or abnormal laboratory value (according to CTCAE criteria) assessed by treating physician as related to study drug (and unrelated to disease progression, intercurrent illness, or concomitant medications) occurring during the first 28 days on study.
A hematologic DLT defined as severe myelosuppression with a hypoplastic marrow with less than 5% cellularity and no evidence of leukemia 42 days from start of therapy.
This will define severe and delayed myelosuppression not related to persistent leukemia and likely related to treatment.
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21 days
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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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Participants With a Response
時間枠：21 days
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A Response is defined as: Complete response (CR) + Complete response without platelet recovery (CRp) + CR with insufficient hematological recovery (platelets or neutrophils (CRi).
CR is Neutrophil count 2: 1.0 x 10^9/L, platelet count 2: 100 x 10^9/L and bone marrow aspirate and biopsy: S5% blasts.
CRp is same as CR but with Platelets < 100 x 10^/L.
CRi is same as CR but platelets < 100 x 10(/L or neutrophils < 1 x 10^9.
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21 days
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協力者と研究者
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 (見積もり)
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
追加の関連 MeSH 用語
その他の研究ID番号
- 2013-0099
- NCI-2013-01665 (レジストリ識別子：NCI CTRP)
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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