NCT01701375终止1 期
A Phase I and Pharmacodynamic Trial of Timed Sequential Administration of the Cyclin Dependent Kinase 4/6 Inhibitor PD 0332991 Followed by Cytarabine Plus Mitoxantrone for Adults With Relapsed and Refractory Acute Leukemias and High-Risk Myelodysplasias
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins2 个研究点 分布在 1 个国家目标入组 2 人开始时间: 2012年9月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- The Toxicities of Administration of PD 0332991 in Combination With Cytarabine and Mitoxantrone.
研究概览
简要总结
1.1 Primary Objectives
- To determine the feasibility, tolerability, and toxicities of administering the selective CDK 4/6 inhibitor PD 0332991 prior to the combination of ara-C and Mitoxantrone for adults with relapsed and refractory acute leukemias and high risk myelodysplasias (MDS), including primary refractory disease
- To determine the direct cytotoxic effects of single agent PD 0332991 on malignant blasts
- To determine the maximal tolerated dose (MTD) of PD 0332991 in timed sequential combination with ara-C and Mitoxantrone
- To determine if the timed sequential combination of PD 0332991 with ara-C and mitoxantrone can induce clinical responses in adults with relapsed or refractory acute leukemias and high-risk MDS
1.2 Secondary Objectives:
- To determine the ability of PD 0332991 to directly induce apoptosis in malignant cell populations in vivo
- To obtain pharmacodynamic (PD) data regarding the ability of PD 0332991 to arrest malignant cells in the G 1 phase of cell cycle, followed by synchronized release of those cells into S phase upon discontinuation of PD 0332991 and resultant enhanced ara-C cytotoxicity
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults age ≥ 18 years
- •Multilineage bone marrow failure
- •Serum creatinine ≤ 2.0 mg/dl
- •Hepatic enzymes (AST, ALT) ≤ 3x upper limit of normal (ULN)
- •Bilirubin ≤ 2.0 mg/dl, unless due to Gilbert's disease, hemolysis or leukemic infiltration
- •Left ventricular ejection fraction ≥ 45%
- •QTc ≤ 470 msec
- •RB expression is required for the action of PD
- •Because rb deletions and mutations are rare in acute leukemias and MDS, screening for RB expression will not be required before enrollment. Pretreatment biopsies will be stored and analyzed for RB expression if needed subsequently.
排除标准
- •• No more than 5 cytotoxic regimens
- •Previous allogeneic or autologous stem cell transplantation permitted
- •≥ 3 weeks delay from prior cytotoxic chemotherapy or radiation therapy
- •≥ 2 week delay from prior biologic therapies including hematopoietic growth factors and vidaza or decitabine
- •If using Hydroxyurea, steroids, tyrosine kinase/src kinase inhibitors, arsenic, interferon for count control, must be off therapy for ≥ 48 hours prior to beginning PD 0332991
- •No concomitant use of potent CYP450 3A4 inhibitors (e.g. triazole antifungal agents) or inducers (e.g. omperazole, dilantin, dexamethasone) within 7 days prior to beginning PD 0332991
研究组 & 干预措施
Arm 1
Experimental
- PD 0332991 will be given orally days 1,2,3
- Cytarabine (ara-C) will be given by continuous 72 hour intravenous infusion beginning on day 6
- Mitoxantrone will be given over 2 hour infusion day 9, 12 hours after the completion of the ara-C infusion. The mitoxantrone dose may be reduced by 25-50% for patients who have received previous anthracyclines as determined by total previous anthracycline dose
干预措施: PD 0332991 (Drug)
结局指标
主要结局
The Toxicities of Administration of PD 0332991 in Combination With Cytarabine and Mitoxantrone.
时间窗: 42 days
The number of participants experiencing toxicities of administration of PD 0332991 in combination with cytarabine and mitoxantrone will be measured according to NCI-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
次要结局
- To Determine the Maximal Tolerated Dose (MTD) of PD 0332991 in Timed Sequential Combination With Ara-C and Mitoxantrone(42 days)
研究者
研究点 (2)
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