A Phase II Study of Metronomic Chemotherapy in Elderly Non-fit Patients (>65 Years) With Aggressive B-Cell Lymphomas
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 10
- 主要终点
- Complete Remission Rate (CRR)
研究概览
简要总结
This is a phase II study of metronomic chemotherapy in elderly non-fit patients (>65 years) with aggressive B-Cell lymphomas
详细描述
Patients eligible for the study will receive 6 courses (q 28 days) of the DEVEC combination, according to the following schedule:
- DE: Prednisone (Deltacortene) 25 mg /day will be orally administered from day 1 to day 28 only in cycle 1 From cycle 2 to 6 it is reduced to three times a week (after breakfast, MON, WED, FRI)
- V: Vinorelbine 30 mg/day will be orally administered three times a week, 3 week on and 1 week off (after breakfast, MON, WED, FRI).
- E: Etoposide 50 mg/day will be orally administered from day 1 to day 14 (before lunch).
- C: Cyclophosphamide 50 mg/day will be orally administered from day 1 to day 21 (after dinner).
- Rituximab: 375 mg/m2 will be administered by IV infusion up to four infusions on days 8, 15, 22, 29, only in patients suitable for infusion treatment and relapsed after >6 months from last R-chemotherapy. Refractory patients who had received at least 5 doses of Rituximab will not repeat it during the metronomic therapy.
Super-frail patients will not receive etoposide during cycles 1 and 2; etoposide will be included in the treatment schedule starting from cycle 3 at reduced dose (50 mg/day, from day 1 to day 7) only in patients who in cycles 1 and 2 didn't experience hematological toxicity >G2 and/or non-hematological toxicity >G1.
In Unfit and Frail patients with hemoglobin level at study entry <11 gr/dL, will start etoposide will be orally administered at reduced dose (50 mg/day from day 1 to day 7). If hemoglobin will raise to ≥11 gr/dL, at subsequent induction cycles etoposide will be administered at full dose (50 mg/day, from day 1 to day 14), As a preventive measure, to avoid perforation, patients with gastrointestinal visceral involvement will receive a pre-phase therapy with steroids (prednisolone 40mg/m2
) for 6-7 days before starting protocol treatment. Moreover, in these patients the four Rituximab doses will be administered in cycle 2.
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
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of aggressive Non-Hodgkin Lymphomas (NHLs) including:
- •Grade IIIb follicular lymphoma;
- •B-Cell unclassifiable lymphomas with features intermediate between DLBCL and BL or between DLBCL and Hodgkin's lymphoma (HL)35;
- •High grade B-cell lymphomas1
- •Age >65 years
- •Unfit or frail patients (the latest defined, for the purpose of this study, as those who have a maximum of 1 frail factor) according to the multidimensional geriatric evaluation model of the elderly platform of the FIL, who relapsed/progressed after one or maximum two previous lines of treatment or
- •"Super-frail" elderly patients at disease onset: eligible super-frail patients are defined, for the purpose of this study, as those who have a maximum of 2 frail factors, according to the CGA adopted in the elderly platform of the FIL, among those below listed:
- •IADL ≤ 5;
- •Age ≥ 80 years;
- •1 CIRS grade 3 or >8 CIRS grade
- •Ann Arbor stage I bulky to IV
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Life expectancy >1-2 months.
- •Adequate renal function (creatinine ≤ 2 mg/dl, unless secondary to lymphoma).
- •Adequate liver function (bilirubin ≤ 2 mg/dl, unless secondary to lymphoma).
- •Absolute neutrophil count (ANC) ≥1500 cells/mmc and platelets ≥ 50,000 cells/mmc, haemoglobin ≥ 9 gr/dl, unless cytopenia is related to bone marrow involvement by lymphoma.
- •Availability of adequate care by family members or other caregivers.
- •Written informed consent signature.
- •Male Subjects must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 3 months following the end or the discontinuation from the study treatment even if he has undergone a successful vasectomy.
排除标准
- •Patients who received more than two previous chemotherapy lines.
- •Relapsed/refractory patients with fit profile.
- •Fit, unfit, and frail patients at disease onset.
- •Malabsorption syndrome or other diseases that affect the ability to swallow oral therapy.
- •Concomitant malignancy requiring treatment (except non-melanoma skin cancers and in situ carcinoma of the uterine cervix).
- •Presence of opportunistic infections in place.
- •Seropositive for or active viral infection with hepatitis B virus (HBV):
- •HBsAg positive;
- •HBsAg negative, HBcAb positive with detectable viral DNA (Subjects who are HBsAg negative, HBcAb positive, but viral DNA negative are eligible.
- •Seropositive and active infection for hepatitis C virus (subjects who are HCV-RNA negative are eligible).
- •Known seropositive for or active viral infection with human immunodeficiency virus (HIV).
- •Impossibility to give written informed consent.
研究组 & 干预措施
One arm for all patient
Induction phase:
Eligible Pts will receive 6 cycles (every 28 days) of the DEVEC combination: DE: Prednisone, V: Vinorelbine, E: Etoposide, C: Cyclophosphamide and R:Rituximab ; R will be administered only in patients suitable for infusion treatment and relapsed after >6 months from last R-chemotherapy. Refractory patients who received at least 5 doses of R will not repeat it during the metronomic therapy.
Super-frail patients will not receive etoposide during cycles 1 and 2.
Maintenance Phase:
Pts in CR, CRu and PR at the end of the induction phase, will continue treatment with maintenance therapy including Vinorelbine, Cyclophosphamide, and Prednisone oral combination to be repeated every 28 days for up to 6 cycles.
Post Maintenance Phase:
Pts in CR/CRu at the EOT may, at discretion of the local investigator, continue maintenance with only Vinorelbine and Prednisone for up to further 12 months, progression or inacceptable toxicity at the same doses of maintenance
干预措施: Prednisone (Drug)
One arm for all patient
Induction phase:
Eligible Pts will receive 6 cycles (every 28 days) of the DEVEC combination: DE: Prednisone, V: Vinorelbine, E: Etoposide, C: Cyclophosphamide and R:Rituximab ; R will be administered only in patients suitable for infusion treatment and relapsed after >6 months from last R-chemotherapy. Refractory patients who received at least 5 doses of R will not repeat it during the metronomic therapy.
Super-frail patients will not receive etoposide during cycles 1 and 2.
Maintenance Phase:
Pts in CR, CRu and PR at the end of the induction phase, will continue treatment with maintenance therapy including Vinorelbine, Cyclophosphamide, and Prednisone oral combination to be repeated every 28 days for up to 6 cycles.
Post Maintenance Phase:
Pts in CR/CRu at the EOT may, at discretion of the local investigator, continue maintenance with only Vinorelbine and Prednisone for up to further 12 months, progression or inacceptable toxicity at the same doses of maintenance
干预措施: Vinorelbine (Drug)
One arm for all patient
Induction phase:
Eligible Pts will receive 6 cycles (every 28 days) of the DEVEC combination: DE: Prednisone, V: Vinorelbine, E: Etoposide, C: Cyclophosphamide and R:Rituximab ; R will be administered only in patients suitable for infusion treatment and relapsed after >6 months from last R-chemotherapy. Refractory patients who received at least 5 doses of R will not repeat it during the metronomic therapy.
Super-frail patients will not receive etoposide during cycles 1 and 2.
Maintenance Phase:
Pts in CR, CRu and PR at the end of the induction phase, will continue treatment with maintenance therapy including Vinorelbine, Cyclophosphamide, and Prednisone oral combination to be repeated every 28 days for up to 6 cycles.
Post Maintenance Phase:
Pts in CR/CRu at the EOT may, at discretion of the local investigator, continue maintenance with only Vinorelbine and Prednisone for up to further 12 months, progression or inacceptable toxicity at the same doses of maintenance
干预措施: Etoposide (Drug)
One arm for all patient
Induction phase:
Eligible Pts will receive 6 cycles (every 28 days) of the DEVEC combination: DE: Prednisone, V: Vinorelbine, E: Etoposide, C: Cyclophosphamide and R:Rituximab ; R will be administered only in patients suitable for infusion treatment and relapsed after >6 months from last R-chemotherapy. Refractory patients who received at least 5 doses of R will not repeat it during the metronomic therapy.
Super-frail patients will not receive etoposide during cycles 1 and 2.
Maintenance Phase:
Pts in CR, CRu and PR at the end of the induction phase, will continue treatment with maintenance therapy including Vinorelbine, Cyclophosphamide, and Prednisone oral combination to be repeated every 28 days for up to 6 cycles.
Post Maintenance Phase:
Pts in CR/CRu at the EOT may, at discretion of the local investigator, continue maintenance with only Vinorelbine and Prednisone for up to further 12 months, progression or inacceptable toxicity at the same doses of maintenance
干预措施: Cyclophosphamide (Drug)
One arm for all patient
Induction phase:
Eligible Pts will receive 6 cycles (every 28 days) of the DEVEC combination: DE: Prednisone, V: Vinorelbine, E: Etoposide, C: Cyclophosphamide and R:Rituximab ; R will be administered only in patients suitable for infusion treatment and relapsed after >6 months from last R-chemotherapy. Refractory patients who received at least 5 doses of R will not repeat it during the metronomic therapy.
Super-frail patients will not receive etoposide during cycles 1 and 2.
Maintenance Phase:
Pts in CR, CRu and PR at the end of the induction phase, will continue treatment with maintenance therapy including Vinorelbine, Cyclophosphamide, and Prednisone oral combination to be repeated every 28 days for up to 6 cycles.
Post Maintenance Phase:
Pts in CR/CRu at the EOT may, at discretion of the local investigator, continue maintenance with only Vinorelbine and Prednisone for up to further 12 months, progression or inacceptable toxicity at the same doses of maintenance
干预措施: Rituximab (Drug)
结局指标
主要结局
Complete Remission Rate (CRR)
时间窗: 30 months
The primary efficacy endpoint is defined in terms of complete response (CR), including complete response unconfirmed (CRu), according to Recommendations of an International Workshop to Standardise Response Criteria for Non-Hodgkin´s Lymphomas.
Incidence of adverse events
时间窗: 30 months
The primary safety endpoint is defined as incidence, nature, and severity of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03
次要结局
- Overall response rate (ORR)(30 months)
- Progression Free Survival (PFS)(36)
- Event Free Survival (EFS)(36)
- Overall Survival (OS)(36)
- Clinical Benefit(30 months)
- Disease Free Survival (DFS)(36)
- Patient-Reported Outcome (PRO)(36)