Purine-Alkylator Combination In Follicular Lymphoma Immuno-Chemotherapy for Older Patients: a Phase III Comparison of First-line R-CVP Versus R-FC
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 680
- 试验地点
- 73
- 主要终点
- Toxicity
研究概览
简要总结
The purpose of this study is to determine whether R-FC is more beneficial that R-CVP in the treatment of older patients (aged 60 or over) with Follicular Lymphoma (FL).
详细描述
FL predominantly affects the elderly, yet the optimum treatment for older patients with the disease has not been defined. The present study aims to address this question by comparing the drug combination that is currently considered the gold-standard (R-CVP) with a newer combination (R-FC) that might be more effective without being significantly more toxic. In order to take into account the balance between efficacy and toxicity, a dual primary endpoint has been employed: progression-free survival and toxicity in the form of grade 3-4 infection.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed follicular lymphoma (grade 1,2, and 3a with material available for central review)
- •Ann Arbor stage II-IV
- •Aged 60 years or over, or aged less than 60 but anthracycline-based therapy contra-indicated
- •No prior systemic therapy (one episode of prior local radiotherapy is allowed)
- •At least one of the following criteria for initiation of treatment:
- •Rapid generalized disease progression in the preceding 3 months
- •Life threatening organ involvement
- •Renal or macroscopic liver infiltration
- •Bone lesions
- •Presence of systemic symptoms or pruritus
- •Haemoglobin < 10 g/dL or WBC < 3.0 × 109/L or platelet counts < 100 × 109/L due to marrow involvement
- •Adequate haematological function (unless abnormalities are related to lymphoma infiltration of the bone marrow):
- •Haemoglobin ≥ 8.0 g/dL
- •Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- •Platelet count ≥ 100 x 109/L
- •Written Informed Consent
排除标准
- •Overt transformation to diffuse large B-cell lymphoma
- •Grade 3b follicular lymphoma
- •Presence or history of CNS disease (either CNS lymphoma or lymphomatous meningitis)
- •WHO performance status 3 or 4
- •Impaired renal function defined as estimated Glomerular filtration rate (eGFR) < 30 mL/min using the Modification of Diet in Renal Disease (MDRD) formula
- •Impaired hepatic function defined as serum bilirubin more than twice upper limit of normal (unless due to lymphoma or Gilbert's syndrome)
- •Life expectancy less than 12 months
- •Pre-existing neuropathy
- •Active auto-immune haemolytic anaemia
- •Serological evidence of infection with HIV, hepatitis B (positivity for surface antigen or core antibody) or hepatitis C
- •Allergy to murine proteins
- •Corticosteroid treatment during the last 4 weeks, unless administered at a dose equivalent to no more than prednisolone 20mg/day continuously or a single course of prednisolone 1 mg/kg for up to 7 days
- •Concomitant malignancies except adequately treated localised non-melanoma skin cancer or adequately treated in situ cervical cancer, or cancers that have been in remission for at least 5 years following surgery with curative intent.
- •Major surgery (excluding lymph node biopsy) within 28 days prior to randomisation
- •Serious underlying medical conditions, which could impair the ability of the patient to participate in the trial (e.g. ongoing infection, uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease)
- •Treatment within a clinical trial within 30 days prior to trial entry
- •Any other co-existing medical or psychological condition that will preclude participation in the study or compromise ability to give informed consent
- •Adult patient under tutelage (not competent to sign informed consent)
- •Pregnant or lactating women
- •All men or women of reproductive potential, unless using at least two contraceptive precautions, one of which must be a condom
研究组 & 干预措施
R-CVP
Repeated every 21 days for up to 8 cycles with response assessment after 4 cycles. Responders (PR/CR) after 8 cycles will receive Rituximab maintenance therapy for 2 years (12 bi-monthly cycles).
干预措施: Rituximab (Drug)
R-CVP
Repeated every 21 days for up to 8 cycles with response assessment after 4 cycles. Responders (PR/CR) after 8 cycles will receive Rituximab maintenance therapy for 2 years (12 bi-monthly cycles).
干预措施: Cyclophosphamide (Drug)
R-CVP
Repeated every 21 days for up to 8 cycles with response assessment after 4 cycles. Responders (PR/CR) after 8 cycles will receive Rituximab maintenance therapy for 2 years (12 bi-monthly cycles).
干预措施: Vincristine (Drug)
R-CVP
Repeated every 21 days for up to 8 cycles with response assessment after 4 cycles. Responders (PR/CR) after 8 cycles will receive Rituximab maintenance therapy for 2 years (12 bi-monthly cycles).
干预措施: Prednisolone (Drug)
R-FC
Repeated every 21 days for 4 cycles. Responders (PR/CR) after 4 cycles will receive 4 further cycles of Rituximab only. Responders after 8 cycles will receive Rituximab maintenance therapy for 2 years (12 bi-monthly cycles).
干预措施: Cyclophosphamide (Drug)
R-FC
Repeated every 21 days for 4 cycles. Responders (PR/CR) after 4 cycles will receive 4 further cycles of Rituximab only. Responders after 8 cycles will receive Rituximab maintenance therapy for 2 years (12 bi-monthly cycles).
干预措施: Fludarabine (Drug)
结局指标
主要结局
Toxicity
时间窗: 36 months
The second primary outcome measure is grade 3-4 infection occurring anytime from the start of treatment until 6 months following the last dose of treatment, and this will be used as the toxicity end-point. Toxicity will be measured according to standard National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 following each cycle of treatment and at each subsequent follow-up visit until 6 months following the last dose of treatment.
Progression-free survival
时间窗: 30 months
次要结局
- Response rates (overall, complete and partial) following initial therapy(24 weeks)
- Response rates following maintenance therapy(30 months)
- Response duration(30 months)
- Overall survival(End of study)
- Time to next treatment(End of study)
- Rate of large cell transformation(End of study)
- Response to second-line therapy(30 months)
- Number of treatment cycles delivered(30 months)
- Cumulative dose of individual drugs administered(30 months)
- Quality of life(End of study)
- Cost effectiveness(End of study)