A Phase I/II of Vorinostat Plus CHOP in Untreated T-cell Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Phase II MTD of Vorinostat
研究概览
简要总结
The goal of this clinical research study is to find out how well the drug Zolinza (vorinostat) works in combination with the drug combination called CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) to treat patients with untreated T-cell Non-Hodgkin's Lymphoma (NHL). The safety of these drugs in combination and the best dose of vorinostat when given in combination with CHOP will also be studied.
详细描述
The Study Drugs:
Vorinostat is designed to cause chemical changes in different groups of proteins that are attached to DNA (the genetic material of cells), which may slow the growth of cancer cells or cause the cancer cells to die.
Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth. This may cause the cancer cells to die.
Doxorubicin is designed to stop the growth of cancer cells, which may cause the cells to die.
Vincristine is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth. This may cause the cancer cells to die.
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
- •Patients must have a new diagnosis of T-cell NHL eligible histologies include:Peripheral T-cell lymphoma (unspecified), CD 30 + anaplastic large cell lymphoma (ALK) (ALK-1 positive and ALK-1 negative), angioimmunoblastic T-cell lymphoma, intestinal T-cell lymphoma, subcutaneous panniculitic T-cell lymphoma.
- •Patients who are eligible for blood and marrow transplant can receive this treatment to maximal reduction of tumor bulk. A minimum of four cycles of therapy will be given before evaluation for to hematopoetic stem cell transplant.
- •Patients must have biopsy proven disease which can include bone marrow and/or lymph node (cutaneous only disease is excluded)
- •Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Patients must be age 18 years old and above.There is no dosing or adverse event data are currently available on the use of vorinostat in patients <18 years of age, children are excluded from this study but may be eligible for future pediatric phase 2 combination trials.
- •There is Patients are required to have adequate bone marrow reserve as indicated: Absolute neutrophil count (ANC) >/= 1000/mm^3, Platelets >/= 50,000/mm3, Hemoglobin >/= 8g/dL. If there is bone marrow involvement by lymphoma then there is no minimum level of counts required.
- •Patients must have adequate liver function as indicated by: Bilirubin </= 1.5 times the upper limit of normal (ULN), Alanine transaminase (ALT) </=2 times the (ULN) or aspartate transaminase (AST) </= 2 times the ULN. These values must be obtained within two weeks before protocol entry.
- •Patients are required to have adequate renal function as indicated by a serum creatinine </= 2.5 mg/dL. This value must be obtained within two weeks before protocol entry.
- •Left ventricular ejection fraction must be evaluated by nuclear medicine scan or echocardiography and measure >/= 50%.
- •Concomitant steroids may continue provided they are being used for symptom management and not for treatment of lymphoma.
- •Male patients must agree to use a barrier method of contraception or agree to abstain from heterosexual activity for the duration of the study
- •Female patients must be willing to use two adequate barrier methods of contraception to prevent pregnancy or agree to abstain from heterosexual activity throughout the study or be post menopausal (free from menses > two years or surgically sterilized).
- •Female patients of childbearing potential must have a negative serum pregnancy test (Beta human chorionic gonadotropin (hCG)) within 72 hours of receiving the first dose of vorinostat.
- •Patients must have the ability able to give informed consent.
排除标准
- •Patients with a) T-cell lymphoma with skin involvement only are excluded if they have no evidence of systemic disease b)T-cell prolymphocytic leukemia (T-PLL) c) T-cell large granular lymphocytic leukemia d) Primary cutaneous CD30+ disorders: anaplastic large cell lymphoma and lymphomatoid papulosis e) Angiocentric/nasal type T/Natural Killer (NK)-cell lymphoma f) Hepatosplenic gamma-delta T-cell lymphoma
- •Patients with active Hepatitis B and/or Hepatitis C infection.
- •Patients with known HIV infection are excluded. a) These patients are excluded secondary to potential to target activated T-cells, in a population of patients already at risk for T-cell depletion, would be a contraindication to therapy.
- •Patients with active infections requiring specific anti-infective therapy are not eligible until all signs of infections are resolved.
- •Patients with pre-existing cardiovascular disease requiring ongoing treatment. This includes:a) Congestive heart failure, b) Severe CAD, c) Cardiomyopathy, d) Uncontrolled cardiac arrhythmia, e) Unstable angina pectoris, f) Recent MI (within 6 months).
- •Patients with prior exposure to either vorinostat (including other histone deacetylase (HDAC) inhibitors except valproic acid) or anthracyclines: a) Patients who have received valproic acid (VPA) for the treatment of seizures may be enrolled on this study, but must not have received VPA within 30 days of study enrollment.
- •Patients who are pregnant or breast-feeding. a)Effects of this treatment on the fetus and young children are unknown at this time.
- •Patients who have had an invasive solid tumor malignancy in the past five years except non-melanoma skin cancers or cervical carcinoma in situ or ductal/lobular carcinoma in situ of the breast who is currently without evidence of disease.
- •Patients undergoing anti-neoplastic chemotherapy, radiation, hormonal (excluding contraceptives) or immunotherapy, or investigational medications within the past four weeks.
- •Patients with deep vein thrombosis within three months.
- •Patient with concurrent use of complementary or alternative medicines.
- •Patients with psychiatric illness and/or social situations that would limit compliance with the study medication and requirements.
- •Patients with grade 2 or more neuropathy.
- •Patients with known central nervous system (CNS) lymphoma.
研究组 & 干预措施
Zolinza + CHOP
Zolinza (vorinostat) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)
干预措施: Zolinza (vorinostat) (Drug)
Zolinza + CHOP
Zolinza (vorinostat) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)
干预措施: Cyclophosphamide (Drug)
Zolinza + CHOP
Zolinza (vorinostat) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)
干预措施: Doxorubicin (Drug)
Zolinza + CHOP
Zolinza (vorinostat) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)
干预措施: Vincristine (Drug)
Zolinza + CHOP
Zolinza (vorinostat) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)
干预措施: Prednisone (Drug)
结局指标
主要结局
Phase II MTD of Vorinostat
时间窗: 21 Days
MTD of Vorinostat when administered in combination with Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) defined as highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT). Continual reassessment during each 21-day cycle to assess dose limiting toxicity. Two schedules of Vorinostat were investigated: Phase I A) daily doses on days 5 to 14, or Phase II B) three times a day on days -2 to 3 of standard CHOP every 21 days. Vorinostat was administered orally on days 5 to 14 (Schedule A), first at 300 mg orally once daily (total doses of 3000 mg over 10 days per cycle), and next at 200 mg orally twice daily (total doses of 4000 mg over 10 days per cycle); Schedule B Vorinostat administered orally 300 mg orally three times daily from days -2 to 3 (4500 mg over 5 days per cycle).
Phase I Maximum Tolerated Dose (MTD) of Vorinostat
时间窗: 21 Days
MTD of Vorinostat when administered in combination with Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) defined as highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT). Continual reassessment during each 21-day cycle to assess dose limiting toxicity. Two schedules of Vorinostat were investigated: Phase I A) daily doses on days 5 to 14, or Phase II B) three times a day on days -2 to 3 of standard CHOP every 21 days. Vorinostat was administered orally on days 5 to 14 (Schedule A), first at 300 mg orally once daily (total doses of 3000 mg over 10 days per cycle), and next at 200 mg orally twice daily (total doses of 4000 mg over 10 days per cycle); and for Phase II Schedule B Vorinostat administered orally 300 mg orally three times daily from days -2 to 3 (4500 mg over 5 days per cycle).
Number of Participants With Dose Limiting Toxicity for Determination Phase I (Schedule A) MTD of Vorinostat
时间窗: 21 Days
MTD of Vorinostat defined as highest dose level in which 6 patients have been treated with less than 2 instances of DLT. Continual reassessment during each 21-day cycle to assess DLT. Vorinostat was administered orally on days 5 to 14 (Schedule A), first at 300 mg orally once daily (total doses of 3000 mg over 10 days per cycle), and next at 200 mg orally twice daily (total doses of 4000 mg over 10 days per cycle. The dose of Vorinostat escalated in successive 3+3 cohorts of participants to determine the MTD.
次要结局
未报告次要终点