A Phase 2 Study of Rituximab, Venetoclax (ABT 199) and Bortezomib in Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Overall response rate (ORR)
研究概览
简要总结
This phase II trial studies how well rituximab, venetoclax, and bortezomib work in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Venetoclax and bortezomib may stop the growth of tumor cells by blocking some of the proteins needed for cell growth. Giving rituximab, venetoclax, and bortezomib may slow or stop the growth of cancer cells in patients with diffuse large B-cell lymphoma.
详细描述
PRIMARY OBJECTIVE:
I. To determine the overall response rate (ORR) of rituximab, venetoclax, and bortezomib in relapsed/refractory diffuse large B-cell lymphoma.
SECONDARY OBJECTIVES:
I. To describe the safety profile of rituximab, venetoclax, and bortezomib in diffuse large B-cell lymphoma (DLBCL).
II. To describe the progression free survival of subjects enrolled to the study.
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
- •Relapsed/refractory DLBCL defined as any of the following:
- •Confirmed DLBCL/Burkitt lymphoma (BL)/B-cell lymphoma, unclassifiable (BCLU) by World Health Organization (WHO) 2016 classification
- •Double hit lymphoma (DHL) phenotype as confirmed by FISH (fluorescent in-situ hybridization) or IHC (immunohistochemistry)
- •Relapsed or progression of disease after at least one prior line of standard rituximab-cyclophosphamide-hydroxydaunorubicin-oncovin-prednisone (R-CHOP), rituximab-etoposide-prednisone-oncovin-cyclophosphamide-hydroxydaunorubicin (R-EPOCH) or other R-CHOP-like therapy
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •No prior treatment with a proteasome inhibitor or prior BCL2 inhibitor
- •No cytotoxic chemotherapy within 2 weeks prior to study treatment
- •Patients who are not candidates for salvage stem cell transplant or patients who are not candidates for CAR-T (chimeric antigen receptor T-cell) therapy, patients who have progressed or relapsed after a salvage transplant or CAR-T therapy are eligible
- •Patients must give informed consent
- •Prior radiation therapy allowed to < 25% of the bone marrow and patients must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia). Patients treated with standard postoperative adjuvant radiation therapy for other cancers are allowed. Prior radiotherapy must be completed 14 days before study entry. Lesions that have been radiated in the advanced setting cannot be included as sites of measurable disease unless clear tumor progression has been documented in these lesions since the end of radiation therapy
- •Patients with lower blood counts due to marrow involvement by DHL will be eligible for the study
- •Absolute neutrophil count (ANC) >= 1,000/uL
- •Platelets >= 50,000/uL
- •Total bilirubin within normal institutional limits
- •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 3 X institutional upper limit of normal (ULN)
- •Creatinine < 1.5 the upper limit of normal
排除标准
- •Patients who have had prior proteasome inhibitor therapy or prior therapy with venetoclax
- •Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- •Serious concomitant systemic disorders (including active infections) that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator
- •Patients with history of hepatitis B with negative viral load are eligible (including latent carriers and patient with history of active disease who required treatment)
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to venetoclax and bortezomib or other agents used in the study
- •Subjects with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) which is not well controlled on antiviral therapy
- •Patients who have received autologous hematopoietic stem cell transplantation within 12 months
- •Subject has received the following within 7 days prior to the first dose of study drug: Steroid therapy for anti-neoplastic intent, strong and moderate CYP3A inhibitors and/or strong and moderate CYP3A inducers
- •The effects of combination venetoclax and bortezomib may cause fetal harm. For this reason, 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, for the duration of study participation and for 12 weeks after. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
研究组 & 干预措施
Treatment (rituximab, venetoclax, bortezomib)
Patients receive rituximab IV on day -1 of cycle 1, then on day 1 of cycles 2-6. Patients also receive venetoclax PO QD on days 1-14 and bortezomib IV or SC on day -1 of cycle 1, then on days 1, 8, and 15 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles for rituximab and up to 26 cycles for venetoclax and bortezomib in the absence of disease progression or unacceptable toxicity.
干预措施: Bortezomib (Drug)
Treatment (rituximab, venetoclax, bortezomib)
Patients receive rituximab IV on day -1 of cycle 1, then on day 1 of cycles 2-6. Patients also receive venetoclax PO QD on days 1-14 and bortezomib IV or SC on day -1 of cycle 1, then on days 1, 8, and 15 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles for rituximab and up to 26 cycles for venetoclax and bortezomib in the absence of disease progression or unacceptable toxicity.
干预措施: Rituximab (Biological)
Treatment (rituximab, venetoclax, bortezomib)
Patients receive rituximab IV on day -1 of cycle 1, then on day 1 of cycles 2-6. Patients also receive venetoclax PO QD on days 1-14 and bortezomib IV or SC on day -1 of cycle 1, then on days 1, 8, and 15 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles for rituximab and up to 26 cycles for venetoclax and bortezomib in the absence of disease progression or unacceptable toxicity.
干预措施: Venetoclax (Drug)
结局指标
主要结局
Overall response rate (ORR)
时间窗: Up to 4 years
Defined as the proportion of subjects who achieve a best response of a partial response (PR) or better. The ORR (complete and partial responses) will be reported as a percentage with a 95% confidence interval. If response is missing for any patients, those patients will still be included in the denominator when reporting the response rate.
次要结局
- Incidence of adverse events(Up to 30 days post treatment)
- Progression free survival (PFS)(From study enrollment to disease progression or death from any cause, assessed up to 4 years)
- Overall survival (OS)(From study enrollment to the date of death from any cause, assessed up to 4 years)
- Complete response (CR) and partial response (PR) rates(Up to 4 years)
- Duration of response (DoR)(From when measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 4 years)
研究者
CINJRegulatory
CINJ Regulatory - The PI is no longer affiliated with Rutgers
Rutgers Cancer Institute of New Jersey