A Phase II Study of Bortezomib (Velcade, PS-341) in Combination With Ifosfamide/Vinorelbine in Pediatric Patients and Young Adults With Refractory/Recurrent Hodgkin Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Complete Response (CR)
研究概览
简要总结
This phase II trial studies the side effects and efficacy of bortezomib with ifosfamide and vinorelbine in children and young adults with Hodgkin's lymphoma that was recurrent or did not respond to previous therapy. Bortezomib is an inhibitor of protein degradation. Bortezomib degrades short-lived regulatory proteins in the cell, and has been reported to increase the tumor cells. Bortezomib may increase the effectiveness of ifosfamide and vinorelbine (two standard drugs given to children with Hodgkin Lymphoma that has come back after initial treatment) by making cancer cells more sensitive to effectiveness of standard chemotherapy by preventing anti-death responses in these drugs. Giving bortezomib together with ifosfamide and vinorelbine tartrate should kill more cancer cells than are killed with ifosfamide and vinorelbine alone.
详细描述
PRIMARY OBJECTIVES:
I. Determine the efficacy and safety of bortezomib (as a chemosensitizing agent) in pediatric patients and young adults with primary refractory Hodgkin's lymphoma (HL) or HL in first relapse.
II. Determine the response rate in patients treated with bortezomib, ifosfamide, and vinorelbine ditartrate (vinorelbine tartrate) (IVB) and compare the response rate to the historical response rate in patients treated with ifosfamide and vinorelbine ditartrate alone.
SECONDARY OBJECTIVES:
I. Determine the overall response rate (complete and partial response) and induction success rate after 2 or 4 courses of therapy and the reinduction rate (complete response) after 4 courses of therapy.
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
- — 至 29 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed Hodgkin's lymphoma at time of relapse or disease progression, meeting all of the following criteria:
- •Stage I-IV disease
- •No morphologically unclassifiable disease
- •Meets 1 of the following criteria:
- •Mixed cellularity
- •Lymphocytic depletion (LD)
- •LD, diffuse fibrosis
- •LD, reticular
- •Lymphocyte predominance (LP)
- •LP, diffuse
- •LP, nodular
- •Nodular sclerosis (NS)
- •NS, cellular phase
- •NS, lymphocytic predominance
- •NS, mixed cellularity
- •Not otherwise specified
- •Primary refractory disease OR disease in first relapse, except for the following:
- •Patients who achieved a complete response after treatment on protocol COG-AHOD0431 who experience a biopsy-proven recurrence after doxorubicin hydrochloride, vincristine, prednisone, and cyclophosphamide without involved-field radiotherapy
- •Patients on the observation-only arm of protocol COG-AHOD0431
- •Any measurable, focal mass lesion of a visceral organ (e.g., liver, spleen, or kidney)
- •Patients with metastatic disease to bone marrow and granulocytopenia, anemia, and/or thrombocytopenia are allowed provided both of the following criteria are met:
- •Platelet count ≥ 20,000/mm³ (platelet transfusion allowed)
- •Hemoglobin ≥ 8 g/dL (packed red blood cell transfusion allowed)
- •Karnofsky performance status (PS) 60-100% (for patients > 16 years of age) OR Lanksy PS 60-100% (for patients =< 16 years of age)
- •Life expectancy >= 2 months
- •Absolute neutrophil count >= 1,000/mm^3
- •Platelet count >= 75,000/mm^3 (transfusion independent) (for patients with no bone marrow involvement)
- •Creatinine =< 1.5 times upper limit of normal (ULN)
- •Creatinine clearance or radioisotope glomerular filtration rate >= 70 mL/min/1.73 m^2
- •AST and ALT =< 2.5 times ULN
- •Bilirubin =< 1.5 times ULN
- •Shortening fraction >= 27% by echocardiogram OR LVEF >= 50% by gated radionuclide study
- •Patients with a seizure disorder are eligible if on a nonenzyme-inducing anticonvulsant and seizures are well controlled
- •No CNS toxicity > grade 2
- •No serious intercurrent illnesses
- •No known hypersensitivity to E. coli-derived proteins, filgrastim (G-CSF), or any component of the study drugs
- •No peripheral neuropathy > grade 1
- •No known hypersensitivity to bortezomib, boron, or mannitol
- •No other concurrent chemotherapy or immunomodulating agents (including steroids)
- •Concurrent corticosteroids allowed for treatment or prophylaxis of anaphylactic reactions
- •No dexamethasone or aprepitant as an antiemetic
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Recovered from prior therapy
- •No prior bortezomib or other proteasome inhibitors
- •At least 3 weeks since prior chemotherapy (4 weeks for nitrosoureas)
- •More than 14 days since prior investigational drugs
- •No concurrent enzyme inducing anticonvulsants that alter p450 metabolism, including phenytoin, carbamazepine, phenobarbital, or other anticonvulsants
- •Benzodiazepine or gabapentin allowed
排除标准
- 未提供
研究组 & 干预措施
Treatment (enzyme inhibitor therapy, chemotherapy)
Patients receive ifosfamide IV continuously over days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, bortezomib IV on days 1, 4, and 8, and filgrastim (G-CSF) IV or subcutaneously beginning on day 6 and continuing until blood counts recover or PBSC are harvested. Treatment repeats every 21 days for up to 2 or 4 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo autologous PBSC harvesting according to institutional guidelines after the second course of therapy.
干预措施: ifosfamide (Drug)
Treatment (enzyme inhibitor therapy, chemotherapy)
Patients receive ifosfamide IV continuously over days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, bortezomib IV on days 1, 4, and 8, and filgrastim (G-CSF) IV or subcutaneously beginning on day 6 and continuing until blood counts recover or PBSC are harvested. Treatment repeats every 21 days for up to 2 or 4 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo autologous PBSC harvesting according to institutional guidelines after the second course of therapy.
干预措施: bortezomib (Drug)
Treatment (enzyme inhibitor therapy, chemotherapy)
Patients receive ifosfamide IV continuously over days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, bortezomib IV on days 1, 4, and 8, and filgrastim (G-CSF) IV or subcutaneously beginning on day 6 and continuing until blood counts recover or PBSC are harvested. Treatment repeats every 21 days for up to 2 or 4 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo autologous PBSC harvesting according to institutional guidelines after the second course of therapy.
干预措施: vinorelbine tartrate (Drug)
Treatment (enzyme inhibitor therapy, chemotherapy)
Patients receive ifosfamide IV continuously over days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, bortezomib IV on days 1, 4, and 8, and filgrastim (G-CSF) IV or subcutaneously beginning on day 6 and continuing until blood counts recover or PBSC are harvested. Treatment repeats every 21 days for up to 2 or 4 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo autologous PBSC harvesting according to institutional guidelines after the second course of therapy.
干预措施: filgrastim (Biological)
结局指标
主要结局
Complete Response (CR)
时间窗: After 2 cycles of treatment
CR is defined as at least 80% reduction in the sum of the products of the perpendicular diameters of each of the nodal masses or return to normal size, along with negative nuclear medicine imaging.
次要结局
- Overall Response Rate(After 2 cycles and 4 cycles)
- Number of Participants With Grade 3 or 4 Toxicity(4 weeks following completion of therapy)
- Rate of Successful PBSC Harvest(After 2 cycles)
- Biological Markers(Before, during, and after treatment)
- Induction Success Rate(After 2 cycles and 4 cycles)