A Randomized Phase II Study of Bortezomib Plus ICE (BICE) Versus Standard ICE for Patients With Relapsed/Refractory Classical Hodgkin Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Overall Response After 3 Cycles of Botezomib Plus ICE (BICE) Versus Ifosfamide, Carboplatin, Etoposide (ICE) in Patients With Relapsed/Refractory Classical Hodgkin Lymphoma
研究概览
简要总结
This phase II trial studies how well combination chemotherapy with or without bortezomib works in treating patients with classical Hodgkin lymphoma that has come back or does not respond to prior treatment. Drugs used in chemotherapy, such as ifosfamide, carboplatin, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bortezomib is designed to block a protein that plays a role in cell function and growth. Bortezomib may cause cancer cells to die. It is not yet known if combination chemotherapy with or without bortezomib may work better in treating patients with classical Hodgkin lymphoma.
详细描述
PRIMARY OBJECTIVES:
I. To determine the objective response rate (ORR), partial remissions (PR), and complete remissions (CR) after 3 cycles of bortezomib plus ifosfamide, carboplatin, and etoposide (ICE) (BICE) versus ICE in patients with relapsed/refractory classical Hodgkin lymphoma (cHL).
II. To evaluate 2-year progression-free survival (PFS) in patients treated with 3 cycles of BICE versus ICE.
SECONDARY OBJECTIVES:
I. To compare positron emission tomography (PET) scan response after 3 cycles of BICE versus ICE chemotherapy.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Relapsed or refractory classical Hodgkin lymphoma.
- •Patients must have received a front-line standard anthracycline-containing regimen, such as adriamycin-bleomycin-vinblastine-dacarbazine (ABVD), Stanford V, or bleomycin-etoposide-adriamycin-cyclophosphamide-oncovin-procarbazine-prednisone (BEACOPP).
- •Bi-dimensionally measurable disease with at least 1 lesion >= 2.0 cm in a single dimension.
- •Absolute neutrophil count (ANC) >= 1,500/microL.
- •Platelet count >= 100,000/ microL.
- •Hemoglobin >= 8 g/dL.
- •Serum bilirubin < 2.0 mg/dL.
- •Alkaline phosphatase < 2 x upper limits of normal (ULN).
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 x ULN.
- •Serum creatinine =< 1.5 mg/dL.
- •Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to
- •Females of childbearing potential must have a negative serum beta-human chorionic gonadotropin (hCG) pregnancy test and must agree to use 2 highly effective contraceptive methods (hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) during the study and for 3 months after completion of protocol treatment. Females of non-childbearing potential are those who are postmenopausal for greater than 1 year or whom have had a bilateral tubal ligation or hysterectomy.
- •Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 3 months after completion of protocol treatment.
- •Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
排除标准
- •Lymphocyte predominant Hodgkin lymphoma histology.
- •More than one prior chemotherapy regimen.
- •Prior autologous or allogeneic stem cell transplant.
- •Presence of central nervous system (CNS) involvement with Hodgkin lymphoma.
- •Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
- •Active hepatitis B or C infection or history of cirrhosis.
- •Grade 2 or greater peripheral neuropathy within 14 days of enrollment.
- •Hypersensitivity to boron or mannitol.
- •Prior bortezomib therapy.
- •Another primary malignancy (other than squamous cell and basal cell carcinoma of the skin, in situ carcinoma of the cervix, or squamous intraepithelial lesion on PAP smear, or treated prostate cancer with a stable prostate specific antigen [PSA]) for which the patient has not been disease-free for at least 3 years.
- •Patients with congestive heart failure, Class III or IV, by New York Heart Association (NYHA) criteria.
- •Patients with a myocardial infarction 6 months prior to enrollment, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiogram (ECG) evidence of acute ischemia or active conduction system abnormalities.
- •Patient with other medical or psychiatric illness that is likely to interfere with participation in this clinical study.
- •Female subject that is pregnant or breast-feeding.
- •Patient that has received other investigational drugs within 14 days of enrollment.
- •Patients using concurrent therapy with corticosteroids at greater than or equal to 20 mg/day of prednisone equivalent.
- •Patients with active systemic bacterial, viral, or fungal infections that have required IV antimicrobials within 4 weeks prior to protocol treatment.
研究组 & 干预措施
Arm A (bortezomib, ifosfamide, carboplatin, etoposide)
ARM A: Patients receive bortezomib IV over 5 seconds on days 1 and 4, ifosfamide IV continuously over 24 hours on day 1, carboplatin IV over 1 hour on day 1, and etoposide IV over 2 hours on days 1-3. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Bortezomib (Drug)
Arm A (bortezomib, ifosfamide, carboplatin, etoposide)
ARM A: Patients receive bortezomib IV over 5 seconds on days 1 and 4, ifosfamide IV continuously over 24 hours on day 1, carboplatin IV over 1 hour on day 1, and etoposide IV over 2 hours on days 1-3. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Carboplatin (Drug)
Arm A (bortezomib, ifosfamide, carboplatin, etoposide)
ARM A: Patients receive bortezomib IV over 5 seconds on days 1 and 4, ifosfamide IV continuously over 24 hours on day 1, carboplatin IV over 1 hour on day 1, and etoposide IV over 2 hours on days 1-3. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Etoposide (Drug)
Arm A (bortezomib, ifosfamide, carboplatin, etoposide)
ARM A: Patients receive bortezomib IV over 5 seconds on days 1 and 4, ifosfamide IV continuously over 24 hours on day 1, carboplatin IV over 1 hour on day 1, and etoposide IV over 2 hours on days 1-3. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Ifosfamide (Drug)
Arm B (ifosfamide, carboplatin, etoposide)
Patients receive ifosfamide, carboplatin and etoposide as in Arm A. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Carboplatin (Drug)
Arm B (ifosfamide, carboplatin, etoposide)
Patients receive ifosfamide, carboplatin and etoposide as in Arm A. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Etoposide (Drug)
Arm B (ifosfamide, carboplatin, etoposide)
Patients receive ifosfamide, carboplatin and etoposide as in Arm A. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Ifosfamide (Drug)
结局指标
主要结局
Overall Response After 3 Cycles of Botezomib Plus ICE (BICE) Versus Ifosfamide, Carboplatin, Etoposide (ICE) in Patients With Relapsed/Refractory Classical Hodgkin Lymphoma
时间窗: From baseline to 3 cycles of treatment
Response rates for Bortezomib, Ifosfamide, Carboplatin, Etoposide (BICE) and Ifosfamide, Carboplatin, Etoposide (ICE) treatment groups were assessed by the 1999 International Working Group (IWG)(CT alone) (Cheson et al., 1999) and compared to 2007 IWG (CT plus PET) (Cheson et al., 2007) criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Progression Free Survival (PFS) Rate at 12 Months
时间窗: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Progression free survival time is defined as the time interval from treatment start to progression or death due to any cause whichever happens first. Participants will be censored at the last follow-up date, if an event(progression/death) is not observed during the follow-up.
Overall Survival (OS) Rate at 24 Months
时间窗: 24 months
Overall Survival is time from date of treatment start until date of death due to any cause or last Follow-up within 24 months.
次要结局
- PET Scan Response After 3 Cycles of BICE Versus ICE Chemotherapy.(Baseline up to 1 year)
- Serum Levels of Tumor Necrosis Factor (TNF) Proteins (APRIL, BLyS, sCD30, and CD40L) and CC Thymus and Activation-related Cytokine (TARC) at Baseline and After 3 Cycles of BICE Versus ICE Chemotherapy(November 2009 and December 2010)
- Baseline Cytokine/Chemokine Levels With Response to Therapy.(106 weeks/13 months/426 days)