NCT02374424终止2 期
Phase II Study With Ga101-DHAP as Induction Therapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL) Patients Before High-Dose Chemotherapy BEAM With Autologous Stem Cell Transplantation (ASCT)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 29
- 试验地点
- 10
- 主要终点
- Aim of this trial is to assess the efficacy of new anti-CD20 antibody (GA101) in association with DHAP as induction therapy before high dose chemotherapy BEAM with ASCT in patients with relapsed/refractory DLBCL.
研究概览
简要总结
Aim of this trial is to assess the efficacy of new anti-CD20 antibody (GA101) in association with DHAP as induction therapy before high dose chemotherapy BEAM with ASCT in patients with relapsed/refractory DLBCL.
详细描述
This is a prospective, multicenter, single arm, phase II trial in young patients (18-65 years) affected by relapsed/refractory Diffuse Large B-cell Lymphoma (DLBCL) at diagnosis,eligible to high-dose therapy.
Aim of the study is to assess whether the addition of GA101 to DHAP is more promising than standard R-DHAP, as induction therapy before high dose chemotherapy BEAM with ASCT with respect to response.
The study is designed primarily to evaluate the efficacy of GA101-DHAP in patients with DLBCL who have relapsed or are refractory to one chemotherapy regimen and secondarily to assess safety and capability to mobilize peripheral stem cells The study is designed with two stages and with stopping rules after the first stage. In particular, at the end of the first stage, the study will be stopped if the efficacy is too low or if the toxicity, measured during the drug administration period, is too high with respect to pre-defined thresholds. .
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •18≥ Age < 65
- •Relapsed/refractory disease after receiving one line of standard R-CHOP like chemotherapy
- •Diffuse Large B-cell Lymphoma at relapse. The re-biopsy is particularly recommended if relapse is over 1 year from previous complete remission. If this is harmful for the patient, the patient can be enrolled if archival tumor sample and block from first diagnosis are available.
- •Measurable and/or evaluable disease
- •Any Ann Arbor stage and IPI group at relapse
- •Performance status < 2 according to Eastern Cooperative Oncology Group (ECOG) scale unless due to lymphoma
- •No Central Nervous System (CNS) disease (meningeal and/or brain involvement by lymphoma)
- •Adequate haematological counts: Absolute Neutrophil Count (ANC) > 1.5 x 109/L, Hgb > 10.5 g/dl (transfusion independent), Platelet count > 75 x 109/L (transfusion independent), with the exception of cytopenia due to lymphoma bone marrow involvement
- •Normal liver function (ALP, AST, ALT, GGT, conjugated bilirubin total < 2 x ULN) if not related to lymphoma
- •Normal kidney function (creatinine clearance >= 80 ml/min)
- •Cardiac ejection fraction > 50% (MUGA scan or echocardiography)
- •Normal lung function
- •Absence of active infections
- •Non peripheral neuropathy or active neurological non neoplastic disease of CNS
- •Non major surgical intervention prior 3 months to randomization if not due to lymphoma and/or not other disease life-threatening that can compromise chemotherapy treatment
- •Disease free of prior malignancies other than lymphoma for > 3 years with exception of currently treated squamous cell and basal cell carcinoma of the skin or carcinoma in situ of the cervix or breast
- •Life expectancy > 6 months
- •No psychiatric illness that precludes understanding concepts of the trial or signing ten informed consent
- •Written informed consent
- •Women must be:
- •postmenopausal for at least 1 year (must not have had a natural menses for at least 12 months)
- •surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy),
- •abstinent (at the discretion of the investigator/per local regulations), or
- •if sexually active, be practicing a highly effective method of birth control (eg, prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method (eg, condoms, diaphragm, or cervical cap, with spermicidal foam, cream, or gel, male partner sterilization) as local regulations permit, before entry, and must agree to continue to use the same method of contraception throughout the study. They must also be prepared to continue birth control measures for at least 18 months after terminating treatment.
- •Women of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening
- •Men must agree to use an acceptable method of contraception (for themselves or female partners as listed above) for the duration of the study. Men must agree to use a double barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug.
排除标准
- •Diagnosis of Lymphoblastic Lymphoma, Burkitt Lymphoma, Non Hodgkin Lymphoma CD20 negative, Mantle Cell Lymphoma, Follicular Lymphoma, Primary Mediastinal Lymphoma
- •Age ≥ 65 years
- •Patients ineligible to high-dose chemotherapy
- •Performance status > 2 according to ECOG scale if not due to lymphoma
- •Patients who previously received GA101 (obinutuzumab) are excluded.
- •Patient has known or suspected hypersensitivity or intolerance to Rituximab
- •Patient has received an experimental drug or used an experimental medical device within 4 weeks before the planned start of treatment. Concurrent participation in nontreatment studies is allowed, if it will not interfere with participation in this study.
- •CNS disease (meningeal and/or brain involvement by lymphoma)
- •History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances
- •Positive test results for chronic hepatitis B infection (defined as positive HBsAg serology). Patients with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HBsAg) may be included if HBV DNA is undetectable. These patients must be willing to undergo monthly DNA testing.
- •Positive test results for hepatitis C (HCV antibody serology testing). Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
- •Known history of HIV seropositive status. For patients with unknown HIV status, HIV testing will be performed at screening if required by local regulations.
- •Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug
- •Uncontrolled or severe cardiovascular disease including myocardial infarction within six months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
- •Cardiac ejection fraction < 45% (MUGA scan or echocardiography)
- •Creatinine clearance < 45 ml/min
- •Presence of major neurological disorders
- •Active infection
- •Major surgical intervention prior 3 months to randomization if not due to lymphoma and/or other disease life-threatening that can compromise chemotherapy treatment
- •Prior malignancies other than lymphoma in the last 3 years with exception of currently treated squamous cell and basal cell carcinoma of the skin or carcinoma in situ of the cervix or breast
- •Life expectancy < 6 months
- •Any other coexisting medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent.
- •If female, the patient is pregnant or breast-feeding.
研究组 & 干预措施
GA101_DHAP
Experimental
Patients receive: GA101-DHAP x 2, restaging, mobilization and collection of peripheral blood stem cells, + GA101-DHAP x 2, restaging with PET and CT and consolidation with BEAM and ASCT in patients in response (CR+PR).
During the treatment period of four cycles, all patients will receive a total of four 28-day courses of chemotherapy.
干预措施: GA101_DHAP (Drug)
结局指标
主要结局
Aim of this trial is to assess the efficacy of new anti-CD20 antibody (GA101) in association with DHAP as induction therapy before high dose chemotherapy BEAM with ASCT in patients with relapsed/refractory DLBCL.
时间窗: 4 months
Primary objective is to assess whether the treatment achieves an absolute increase of the CR proportion of at least 20% (from 30% to 50%) with respect to the standard treatment. The complete response rate (CR) evaluated by PET scan after four cycles of GA101-DHAP before ASCT according to Cheson criteria.
次要结局
- Overall Response Rate (ORR) prior to consolidation with BEAM and ASCT(2 years)
- Progression free survival (PFS) at 6 month after the end of treatment (EOT)(6 month)
- Overall Survival (OS) at 2 years after the EOT(2 years)
- Toxicity: Severe, life-threatening, fatal (grade 3, 4 and 5) and/or serious adverse events(2 years)
- The hematopoietic cell mobilization(2 years)
- Feasibility: the rate of patients actually proceeding to ASCT(2 years)
研究者
研究点 (10)
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