A Randomized Phase 2 Study of Rituxan Hycela in Patients With Advanced Melanoma Undergoing Combination Immune Checkpoint Blockade With Nivolumab and Ipilimumab
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Number of Participants With Common Terminology Criteria (CTC) (Version [v]5.0) Grade 3 or Greater Immune-related Adverse Events
研究概览
简要总结
This phase II trial studies whether rituximab and hyaluronidase human (Rituxan Hycela) can prevent immune related adverse events in participants with stage III-IV melanoma that cannot be removed by surgery who are undergoing nivolumab and ipilimumab therapy.
详细描述
PRIMARY OBJECTIVE:
I. To compare rates for grade 3-4 immune-related adverse event (IRAE)s in the first 6 months in patients treated with combination checkpoint blockade (CCB) therapy (anti-CTLA4 and anti-PD1) as a part of standard of care for advanced melanoma who are treated with a single course of 4 weekly doses of rituximab and hyaluronidase human (Rituxan) therapy versus those who are not treated with Rituxan.
SECONDARY OBJECTIVES:
I. To evaluate the safety and tolerability (in terms of Rituxan-related adverse events) in patients with melanoma receiving CCB.
II. To compare objective response rate in patients receiving CCB therapy + Rituxan versus CCB therapy alone.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Clinically eligible to receive Food and Drug Administration (FDA) approved standard of care combination immune checkpoint therapy with ipilimumab and nivolumab for unresectable stage III or stage IV melanoma.
- •No therapy with immune checkpoint inhibitors within 1 year prior to starting combination checkpoint therapy. Prior adjuvant ipilimumab, nivolumab, or pembrolizumab as single agent is allowed if greater than 1 year since last treatment and patient had no grade 3 or 4 toxicities from the checkpoint inhibitors. History of adjuvant interferon is allowed.
- •Obtained within one week prior to randomization:
- •White blood count ≥ 3,000/µL
- •Absolute neutrophil count (ANC) ≥ 1,500/µL
- •Platelet count ≥ 100,000/µL
- •Hemoglobin ≥ 9 g/dL
- •Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN) or serum creatinine clearance (CrCl) ≥ 40 ml/min
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN (≤ 5 x ULN for patients with documented liver metastases)
- •Alkaline phosphatase ≤ 2 X ULN (≤ 5 X ULN for those with bone metastasis)
- •Total bilirubin ≤ 1.5 X ULN except those with direct bilirubin or Gilbert's syndrome
- •Serum lactate dehydrogenase (LDH) ≤ 10 X ULN
排除标准
- •Allergy to rituximab, or any of the ingredients in rituximab injection or rituximab and hyaluronidase human injection.
- •Patients with active central nervous system (CNS) metastatic disease or leptomeningeal disease. Patients with CNS metastatic disease that has been treated with surgical resection or stereotactic radiosurgery are eligible if lesions are stable for at least 4 weeks following therapy as determined by magnetic resonance imaging (MRI) scan done within one week of randomization.
- •Prior therapy with immune checkpoint blocking antibodies (unless monotherapy given at least 1 year prior to starting combination therapy and no grade 3-4 toxicities while on monotherapy), vaccines or interleukin-2 (IL-2).
- •Patients may have had prior systemic therapy in the adjuvant setting (e.g. interferon, proto-oncogene B-Raf [BRAF], or mitogen-activated protein-extracellular signal-regulated kinase [MEK] agents). Adjuvant ipilimumab, nivolumab, or pembrolizumab as single agent is allowed if greater than 1 year since last treatment and patient had no grade 3 or 4 toxicities from the checkpoint inhibitors.
- •Women must not be pregnant or lactating. Must have negative urine or blood pregnancy test within 1 week of starting therapy.
- •Patients with known human immunodeficiency virus (HIV) are ineligible.
- •Patients with active Hepatitis B Virus (HBV) or Hepatitis C virus (HCV) are ineligible. -- ----Patients with prior history of, or serology suggestive of prior infection with Hepatitis B Virus (HBV) or Hepatitis C virus (HCV) are also ineligible.
- •Patients with active, known or suspected autoimmune disorders including lupus and type I diabetes are ineligible. Patients with history of vitiligo, thyroiditis are eligible.
- •Patients with active disease or history of inflammatory bowel disease are ineligible.
- •Patients cannot be on corticosteroid therapy except as physiologic replacement therapy.
- •Patients receiving ongoing corticosteroid therapy for autoimmune disorders are ineligible. Occasional steroid inhaler use or nasal spray are allowed. Patients receiving replacement doses of steroids for adrenal insufficiency are eligible.
- •Patients must not have any serious underlying medical conditions or take medications that in the investigators opinion may interfere with compliance or interpretation of Immune-related adverse events (IRAEs).
研究组 & 干预措施
Arm A (standard of care)
This is standard of care arm: induction with 4 cycles (21 days each) of Ipilimumab and nivolumab followed by continuation with nivolumab alone every month X1 year (13 doses).
干预措施: Nivolumab (Drug)
Arm A (standard of care)
This is standard of care arm: induction with 4 cycles (21 days each) of Ipilimumab and nivolumab followed by continuation with nivolumab alone every month X1 year (13 doses).
干预措施: Ipilimumab (Drug)
Arm B (rituximab, hyaluronidase human)
This includes induction with 4 cycles of ipilimumab and nivolumab X 4 cycles followed by continuation with nivolumab alone every month for 1 year as in standard of care arm. Each induction cycle is 21 days and includes ipilimumab on day 1 plus nivolumab on day 1. In addition, patients will receive 4 weekly doses of Rituxan (first dose intravenously and then 3 weekly doses subcutaneously). First dose of Rituxan will be administered one week following the start of cycle 1 of ipilimumab and nivolumab. All treatments will have a +/-3 business day window for administration.
干预措施: Nivolumab (Drug)
Arm B (rituximab, hyaluronidase human)
This includes induction with 4 cycles of ipilimumab and nivolumab X 4 cycles followed by continuation with nivolumab alone every month for 1 year as in standard of care arm. Each induction cycle is 21 days and includes ipilimumab on day 1 plus nivolumab on day 1. In addition, patients will receive 4 weekly doses of Rituxan (first dose intravenously and then 3 weekly doses subcutaneously). First dose of Rituxan will be administered one week following the start of cycle 1 of ipilimumab and nivolumab. All treatments will have a +/-3 business day window for administration.
干预措施: Rituximab and Hyaluronidase Human (Biological)
Arm B (rituximab, hyaluronidase human)
This includes induction with 4 cycles of ipilimumab and nivolumab X 4 cycles followed by continuation with nivolumab alone every month for 1 year as in standard of care arm. Each induction cycle is 21 days and includes ipilimumab on day 1 plus nivolumab on day 1. In addition, patients will receive 4 weekly doses of Rituxan (first dose intravenously and then 3 weekly doses subcutaneously). First dose of Rituxan will be administered one week following the start of cycle 1 of ipilimumab and nivolumab. All treatments will have a +/-3 business day window for administration.
干预措施: Ipilimumab (Drug)
结局指标
主要结局
Number of Participants With Common Terminology Criteria (CTC) (Version [v]5.0) Grade 3 or Greater Immune-related Adverse Events
时间窗: At 6 months after study start
All patients will be evaluable for toxicity from the time of their first treatment with ipilimumab/nivolumab. Investigators will review the toxicities, grade, and attribute each toxicity.
次要结局
- Rate of Progression-free Survival (PFS)(From start of treatment up to 1 year)
- Rate of CTC (v5.0) Toxicity Related to Rituximab and Hyaluronidase Human(Up to 4 weeks after study start)
- Rate of Overall Survival(From start of treatment up to 1 year)
- Objective Tumor Response(At 12 weeks and every 12 weeks thereafter up to 1 year)
研究者
Kavita Dhodapkar
Principal Investigator
Emory University