Carfilzomib Consolidation Therapy After Autologous Stem Cell Transplantation (ASCT) for Patients With Mantle Cell (MCL), T-cell (TCL), and Diffuse B-Cell Lymphoma (DLBCL)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Carfilzomib (CFZ) After Autologous Stem Cell Transplantation (ASCT)
研究概览
简要总结
The goal of this clinical research study is to find the highest tolerable dose of carfilzomib that can be given to patients with lymphoma after a stem cell transplant. The safety of this drug will also be studied.
Carfilzomib is designed to block cancer cells from repairing themselves. If the cancer cells cannot repair themselves, this may cause them to die.
详细描述
Study Groups:
If you agree to take part in this study, you will be assigned to a dose level of carfilzomib based on when you joined this study. Up to 4 dose levels of carfilzomib will be tested. Three (3) participants will be enrolled at each dose level until the highest tolerable dose level is found. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. When the highest tolerable dose is found, more participants may be enrolled at that dose level.
Study Treatment:
Each study cycle is 28 days.
On Days 1, 2, 15, and 16 of each cycle, you will receive carfilzomib by vein over 30 minutes. You will receive hydration by vein before and after each infusion of carfilzomib in Cycle 1. This may be repeated in Cycle 2, if your doctor thinks it is needed. On these days during Cycles 1 and 2, before you receive carfilzomib you will receive dexamethasone by vein or as a tablet by mouth. Dexamethasone may help prevent possible infusion reactions. You may continue to receive dexamethasone before each dose of each cycle depending how well you tolerate the infusion.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with mantle cell lymphoma, T-cell lymphoma, and diffuse large b-cell lymphoma within 6 months post autologous transplantation and without relapse.
- •Age >/= 18 years to </= 70 years.
- •Absolute neutrophil count (ANC) >/= to 1.5 x 10^9/L; Platelets > 75 x 10^9/L.
- •No active infection.
- •Performance status: Eastern Cooperative Oncology Group (ECOG) 2 or less or Karnofsky of at least
- •Cardiac EF >/= 45% by 2D-Echo.
- •Serum creatinine less than 1.6 mg/dl and Creatinine Clearance >/= to 30 mL/min.
- •Liver function tests less than 2x upper limit of normal range (unless related to medications or Gilbert's disease).
- •Females of childbearing potential who are not pregnant or breastfeeding.
- •Patient or legally authorized representative able to sign informed consent.
排除标准
- •Glucocorticoid therapy (prednisone >30 mg/day or equivalent within 14 days of first dose.
- •POEMS syndrome.
- •Plasma cell leukemia or circulating plasma cells >/= 2 X 10^9/L.
- •Waldenstrom's Macroglobulinemia.
- •Patients with known amyloidosis.
- •Immunotherapy or chemotherapy with approved or investigational anticancer therapeutics within 21 days of first dose.
- •Patients previously randomized in any other Onyx-sponsored Phase 3 trial.
- •Active congestive heart failure (NYHA Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 6 months.
- •Acute active infection requiring systemic antibiotics, antiviral (except antiviral directed at Hepatitis B) or antifungal agents within 14 days of first dose.
- •Known HIV seropositive, hepatitis C infection, and/or hepatitis B (except for patients with hepatitis B SAg or core antibody receiving and responding to antiviral therapy directed at hepatitis B: these patients are allowed).
- •Patients with known cirrhosis.
- •Second malignancy within past three years except: a. adequately treated basal or squamous cell skin cancer. b. carcinoma in situ of the cervix. c. prostate cancer < Gleason Score 6 with stable prostatic specific antigen (PSA) over the past three months. d. breast cancer in situ with full surgical resection. e. treated medullary or papillary thyroid cancer.
- •Patients with myelodysplastic syndrome.
- •Significant neuropathy (Grades 3 to 4, or Grade 2 pain).
- •Known hypersensitivity to carfilzomib.
- •Known contraindication to dexamethasone.
- •Pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days of first dose.
- •Any other clinically significant medical disease or psychiatric condition that, in the Investigator's opinion, may interfere with protocol compliance.
研究组 & 干预措施
Carfilzomib
Carfilzomib given in four doses, days 1, 2, 15 and 16, every 28 days for 6 months starting within 6 months post ASCT. Doses given in an escalated phase 1 design, starting at 20/20 mg/m2, later increased to 20/27 mg/m2, 20/36 mg/m2 and 20/45 mg/m2. CFZ dose based on actual body surface area at baseline (cycle 1). Patients with a body surface area (BSA) greater than 2.2 m2 receive dose based upon a 2.2 m2 BSA. Adjustments are not made if weight gains or losses are less than or equal to 20% from baseline. Dexamethasone 4 mg by vein or mouth prior to each CFZ dose in cycle 1 and 2 to prevent infusion reactions. After dexamethasone is stopped, then it should be restarted and administered prior to subsequent doses for reactions.
干预措施: Carfilzomib (Drug)
Carfilzomib
Carfilzomib given in four doses, days 1, 2, 15 and 16, every 28 days for 6 months starting within 6 months post ASCT. Doses given in an escalated phase 1 design, starting at 20/20 mg/m2, later increased to 20/27 mg/m2, 20/36 mg/m2 and 20/45 mg/m2. CFZ dose based on actual body surface area at baseline (cycle 1). Patients with a body surface area (BSA) greater than 2.2 m2 receive dose based upon a 2.2 m2 BSA. Adjustments are not made if weight gains or losses are less than or equal to 20% from baseline. Dexamethasone 4 mg by vein or mouth prior to each CFZ dose in cycle 1 and 2 to prevent infusion reactions. After dexamethasone is stopped, then it should be restarted and administered prior to subsequent doses for reactions.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Carfilzomib (CFZ) After Autologous Stem Cell Transplantation (ASCT)
时间窗: 56 days
Maximum tolerated dose (MTD) defined as dose with a posterior probability of treatment-related dose-limiting toxicity (DLT) during the first 56 days closest to the target of 30%. DLT defined as: equal or greater than Grade (G) 2 neuropathy with pain, equal or greater than G3 non-hematologic toxicity, G4 neutropenia greater than 7 days, febrile neutropenia, G4 thrombocytopenia lasting for more than 7 days despite withholding CFZ, G3/4 thrombocytopenia with bleeding, or equal or greater than Grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal antiemetic/antidiarrheal by day 56.
次要结局
- Efficacy of Carfilzomib (CFZ) After Autologous Stem Cell Transplantation (ASCT)(2 years)