Phase I/IIA Study of the Novel Antifolate Agent Pralatrexate in Combination With the Histone Deacetylase Inhibitor Romidepsin for the Treatment of Patients With Peripheral T-cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 57
- 试验地点
- 3
- 主要终点
- Maximum tolerated dose (MTD) of the combination of pralatrexate and romidepsin
研究概览
简要总结
This is a study to test how safe the combination of the drugs Romidepsin and Pralatrexate are in patients with lymphoid malignancies and to determine the dose of the combination of drugs that is safest. If the combination is determined to be safe, the study will continue accrual patients with peripheral T-Cell lymphoma (PTCL).
详细描述
The non- Hodgkin lymphomas (NHL) represent a heterogeneous group of malignancies. Under the rubric of lymphoma exist some of the fastest growing cancers known to science, (Burkett's lymphoma, lymphoblastic lymphoma/leukemia), as well as some of the most indolent (small lymphocytic lymphoma, follicular lymphoma, and marginal zone lymphoma). This remarkable diversity of biology imposes significant challenges. Researchers are seeking to understand the cell of origin and differentiate what are sometimes subtle differences between the related sub-types of disease; and to identify the best treatments for these subtypes, with the ever-increasing likelihood that new understanding of the molecular pathogenesis of these diseases will result in an increase in new drugs for specific target populations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Phase I: Patients must have histologically confirmed relapsed or refractory Non-Hodgkin's lymphoma, Hodgkin's Disease or multiple myeloma (defined by World Health Organization (WHO) criteria).
- •Phase II: Patients must have histologically confirmed relapsed or refractory T-Cell Lymphoma (as defined by WHO criteria).
- •Must have received first line chemotherapy. No upper limit for the number of prior therapies
- •Evaluable Disease
- •Age ≥18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤2
- •Patients must have adequate organ and marrow function as defined in the protocol
- •Adequate Contraception
- •Ability to understand and the willingness to sign a written informed consent document
- •Inclusion Criteria for Multiple Myeloma patients specified in the protocol
排除标准
- •Prior Therapy
- •Exposure to chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier
- •Systemic steroids that have not been stabilized to the equivalent of ≤10 mg/day prednisone prior to the start of the study drugs
- •No other investigational agents are allowed
- •Central nervous system metastases, including lymphomatous meningitis
- •History of allergic reactions to Pralatrexate or Romidepsin
- •Uncontrolled intercurrent illness
- •Pregnant women
- •Nursing women
- •Current malignancy or history of a prior malignancy, as outlined in the protocol
- •Patient known to be Human Immunodeficiency Virus (HIV)-positive
- •Active Hepatitis A, Hepatitis B, or Hepatitis C infection
研究组 & 干预措施
Phase I: Schedule A
Subjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 8 of each 21 day cycle
干预措施: Pralatrexate (Drug)
Phase I: Schedule A
Subjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 8 of each 21 day cycle
干预措施: Romidepsin (Drug)
Phase I: Schedule B
Subjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 15 of each 28 day cycle
干预措施: Pralatrexate (Drug)
Phase I: Schedule B
Subjects will receive dose escalation of pralatrexate and romidepsin, receiving both infusions on days 1 and 15 of each 28 day cycle
干预措施: Romidepsin (Drug)
Phase II
Subjects will receive Pralatrexate 25 mg/m2 and Romidepsin 12 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle
干预措施: Pralatrexate (Drug)
Phase II
Subjects will receive Pralatrexate 25 mg/m2 and Romidepsin 12 mg/m2 will be given intravenously once weekly on days 1 and 15 on a 28 day cycle
干预措施: Romidepsin (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) of the combination of pralatrexate and romidepsin
时间窗: Up to 1.5 years
For Phase I
Overall response rate (ORR) (complete + partial response) of the combination of pralatrexate and romidepsin in patients with relapsed/refractory T-Cell Lymphoma
时间窗: Up to 3 years
For Phase II
次要结局
- Maximum number of cycles received(Up to 1.5 years)
- Number of dose delays at the MTD(Up to 1.5 years)
- Overall survival (OS) of patients with T-Cell Lymphoma on study(Up to 3 years)
- Overall response rate (ORR) of the study population(Up to 1.5 years)
- Duration of response (DOR) of the combination in patients with T-Cell Lymphoma(Up to 3 years)
- Duration of response (DOR) of the study population.(Up to 1.5 years)
- Progression free survival (PFS) of the combination in patients with T-Cell Lymphoma(Up to 3 years)
- Number of dose reductions at the MTD(Up to 1.5 years)
- Progression free survival (PFS) of the study population(Up to 1.5 years)
研究者
Jennifer Amengual
Assistant Professor of Medicine
Columbia University