Phase II Trial of Bortezomib and Vorinostat in Mantle Cell and Diffuse Large B-Cell Lymphomas
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 12
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
This phase II trial studies how well bortezomib and vorinostat work in treating patients with recurrent mantle cell lymphoma or recurrent and/or refractory diffuse large B-cell lymphoma. Bortezomib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
详细描述
This was a multicenter, non-randomized phase 2 trial using a Simon two-stage design with 3 cohorts.
PRIMARY OBJECTIVES:
I. Estimate the response rates of mantle cell and diffuse large B-cell lymphomas to bortezomib and vorinostat combination therapy.
SECONDARY OBJECTIVES:
I. Assess the safety and tolerability of the study regimen. II. Observe progression-free survival and response durations. III. Observe the relationship between pretreatment lymphoma cell nuclear v-rel reticuloendotheliosis viral oncogene homolog A (relA) and response.
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 mantle cell or diffuse large B-cell lymphoma; histological material must be available for central pathological review; unstained histological material -- slides or blocks -- must be available for correlative studies; archived material from previous biopsies is acceptable, unless a patient's lymphoma has been known to undergo histological transformation in the past, in which case a repeat biopsy to confirm histology prior to enrollment is required; availability of material must be confirmed at the time of registration, but material may be submitted subsequent to registration and initiation of study treatment
- •Measurable disease according to the Revised Response Criteria for Malignant Lymphoma; this requires at least one lesion greater than 1.0 cm in diameter in both the long and short axis as measured by spiral computed tomography (CT) scan or physical exam
- •Prior allogeneic stem cell transplant is allowed provided that all of the following conditions are met:
- •>= 6 months have elapsed since allogeneic transplant
- •No graft vs. host disease (GVHD) is present
- •Not currently on immunosuppressive therapy
- •Prior therapy:
- •Mantle cell lymphoma:
- •Previously treated or untreated
- •No prior bortezomib
- •Diffuse large B-cell lymphoma:
- •At least one prior systemic therapy
- •No prior bortezomib
- •Note: Not intended for patients in first relapse who are candidates for high dose therapy with stem cell support
- •Life expectancy of greater than 3 months
- •Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
- •Able to tolerate loperamide or other anti-diarrheal medications
- •Absolute neutrophil count >= 1.5 x 10^9/L
- •Platelets >= 75 x 10^9/L
- •Total bilirubin =< 1.5 x upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transferase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
- •Creatinine within normal institutional limits or calculated creatinine clearance >= 60 mL/min according to the Cockcroft-Gault formula
- •For patients with known human immunodeficiency virus (HIV) infection, a cluster of differentiation (CD)4 count >= 0.5 x 10^9/L
- •For patients whose last treatment included bendamustine or fludarabine, a CD4 count >= 0.4 x 10^9/L
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and to report pregnancy or suspected pregnancy while participating in the study
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Chemotherapy or large field radiotherapy within 3 weeks prior to entering the study
- •Prior histone deacetylase inhibitor as cancer treatment
- •Concurrent treatment with other investigational agents
- •Plans for other concurrent cancer treatment; if steroids for cancer control have been used, patients must be off these agents for >= 1 week before starting treatment; exception: maintenance therapy for non-malignant disease with prednisone or steroid equivalent dose < 10 mg/day is permitted
- •History of brain metastasis including leptomeningeal metastasis
- •Grade >= 2 neuropathy, regardless of cause
- •Unable to take oral medications
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to bortezomib or vorinostat
- •Not sufficiently recovered from previous treatment
- •Medical or other condition (for example: uncontrolled infection; potentially life threatening changes on electrocardiogram [EKG]) or concurrent treatment (for example, marrow suppressive agents such as zidovudine) that represents an inappropriate risk to the patient or likely would compromise achievement of the primary study objective; patients should be closely monitored when given bortezomib in combination with the cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors and inducers
- •Pregnant women are excluded from this study; breastfeeding should be discontinued
- •Active concurrent malignancy, except adequately treated non-melanoma skin cancer
研究组 & 干预措施
Treatment (vorinostat, bortezomib)
Participants receive vorinostat orally (PO) once daily (QD) on days 1-5 and 8-12. Participants also receive bortezomib intravenously (IV) over 3-5 seconds on days 1, 4, 8, and 11. Vorinostat precedes bortezomib on days of concurrent administration. Courses repeat every 3 weeks in the absence of disease progression - or unacceptable toxicity. After completion of study therapy, participants are followed periodically.
Treatment arm consists of 3 cohorts, all receiving the same treatment:
A: Mantle Cell Lymphoma (MCL) - with no prior bortezomib.
B: Mantle Cell Lymphoma (MCL) - with no prior bortezomib.
C: Diffuse Large B-Cell Lymphoma (DLBCL) - with no prior bortezomib.
干预措施: Bortezomib (Drug)
Treatment (vorinostat, bortezomib)
Participants receive vorinostat orally (PO) once daily (QD) on days 1-5 and 8-12. Participants also receive bortezomib intravenously (IV) over 3-5 seconds on days 1, 4, 8, and 11. Vorinostat precedes bortezomib on days of concurrent administration. Courses repeat every 3 weeks in the absence of disease progression - or unacceptable toxicity. After completion of study therapy, participants are followed periodically.
Treatment arm consists of 3 cohorts, all receiving the same treatment:
A: Mantle Cell Lymphoma (MCL) - with no prior bortezomib.
B: Mantle Cell Lymphoma (MCL) - with no prior bortezomib.
C: Diffuse Large B-Cell Lymphoma (DLBCL) - with no prior bortezomib.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (vorinostat, bortezomib)
Participants receive vorinostat orally (PO) once daily (QD) on days 1-5 and 8-12. Participants also receive bortezomib intravenously (IV) over 3-5 seconds on days 1, 4, 8, and 11. Vorinostat precedes bortezomib on days of concurrent administration. Courses repeat every 3 weeks in the absence of disease progression - or unacceptable toxicity. After completion of study therapy, participants are followed periodically.
Treatment arm consists of 3 cohorts, all receiving the same treatment:
A: Mantle Cell Lymphoma (MCL) - with no prior bortezomib.
B: Mantle Cell Lymphoma (MCL) - with no prior bortezomib.
C: Diffuse Large B-Cell Lymphoma (DLBCL) - with no prior bortezomib.
干预措施: Vorinostat (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: Up to 9 years
ORR: Complete Response (CR) + Partial Response (PR) assessed according to the Revised Response Criteria for Malignant Lymphoma.
次要结局
- Progression-free Survival (PFS)(Up to 9 years)
- Duration of Partial Response(Up to 9 years)
- Duration of Stable Disease(Up to 9 years)
- Best Response(Up to 9 years)