A Phase I Trial of Combination Bryostatin-1 and Vincristine in HIV-Related B-cell Neoplasms
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- MTD of bryostatin-1 defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity
研究概览
简要总结
Phase I trial to study the effectiveness of bryostatin 1 plus vincristine in treating patients who have recurrent or refractory lymphoma. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Bryostatin 1 may help vincristine kill more cancer cells by making them more sensitive to the drug
详细描述
OBJECTIVES:
I. Determine the maximum tolerated dose of bryostatin 1 when administered with vincristine in patients with recurrent or refractory HIV-related B-cell lymphoma.
II. Determine the toxicity profile of this regimen in these patients. III. Determine the objective response and survival of these patients treated with this regimen.
IV. Determine the immunomodulatory effects of this regimen on interleukin-2 (IL-2), IL-2 receptor, and IL-6 cytokine levels in these patients.
V. Determine the effect of this regimen on CD4+ lymphocyte count and HIV load in these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Histologically confirmed B-cell lymphoma
- •Eligible subtypes:
- •Intermediate or high-grade non-Hodgkin's lymphoma (NHL), defined as follicular large cell, mantle cell, diffuse mixed cell, diffuse large cell and variants, Burkitt or Burkitt-like, or unclassifiable aggressive histologies
- •Body cavity-based lymphoma or primary effusion lymphoma
- •Evidence of HIV infection
- •Received at least 1 prior systemic chemotherapy regimen with failure to respond or relapse after completion of first-line therapy, including one of the following doxorubicin-based combinations:
- •Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)
- •Infusional cyclophosphamide, doxorubicin, and etoposide (CDE)
- •Etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH)
- •Evaluable disease outside of prior radiation port
- •No CNS parenchymal or leptomeningeal involvement
- •No primary CNS NHL
- •No HTLV-1-associated leukemia or lymphoma
- •Performance status - Karnofsky 70-100%
- •At least 12 weeks
- •Absolute granulocyte count at least 1,000/mm3
- •Platelet count at least 75,000/mm3
- •Hemoglobin at least 8.0 g/dL
- •Bilirubin no greater than 1.5 mg/dL (unless concurrently on indinavir)
- •SGOT and SGPT less than 3 times upper limit of normal
- •Creatinine no greater than 1.5 mg/dL
- •Creatinine clearance at least 50 mL/min
- •No history of cardiac disease
- •LVEF at least 45% by radionuclide ventriculography
- •No symptomatic congestive heart failure
- •No active angina pectoris
- •No uncontrolled hypertension
- •No history of symptomatic pulmonary disease
- •Corrected DLCO more than 50% predicted
- •No severe chronic obstructive lung disease
- •No symptomatic restrictive lung disease
- •Recurrent controllable infection (e.g., thrush) on chronic suppressive therapy allowed
- •No active uncontrolled infection
- •No active significant opportunistic infection (e.g., acute Pneumocystis pneumonia, cytomegalovirus retinitis on induction or maintenance therapy, acute toxoplasmosis)
- •No grade 2 or greater peripheral neuropathy
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective barrier contraception
- •At least 24 hours since prior transfusion
- •At least 24 hours since prior colony-stimulating factor therapy
- •No concurrent prophylactic filgrastim (G-CSF)
- •See Disease Characteristics
- •No concurrent hydroxyurea
- •See Disease Characteristics
- •At least 4 weeks since prior large-field radiotherapy
- •At least 3 weeks since prior anticancer therapy and recovered
- •Must be receiving stable antiretroviral regimen of at least 4 weeks duration
排除标准
- 未提供
研究组 & 干预措施
Treatment (bryostatin 1, vincristine sulfate)
Patients receive bryostatin 1 IV continuously on days 1 and 15 and vincristine IV over 5 minutes on days 2 and 16. Treatment continues every 4 weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: bryostatin 1 (Drug)
Treatment (bryostatin 1, vincristine sulfate)
Patients receive bryostatin 1 IV continuously on days 1 and 15 and vincristine IV over 5 minutes on days 2 and 16. Treatment continues every 4 weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity.
干预措施: vincristine sulfate (Drug)
结局指标
主要结局
MTD of bryostatin-1 defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity
时间窗: 4 weeks
次要结局
- Dose-limiting toxicities(4 weeks)
- Immunomodulatory effects of this combination(Up to 2 years)