A Multicenter Phase IB Dose Escalation Study to Evaluate the Safety, Feasibility and Efficacy of the Torisel-Rituximab-Cyclophosphamide-Doxorubicin-Vincristine-Prednisone (T-R-CHOP), Torisel-Rituximab-Fludarabine-Cyclophosphamide (T-R-FC) and Torisel-Rituximab-Aracytine High Dose-Dexamethasone (T-R-DHA) for the Treatment of Patients in Relapsed/Refractory Mantle Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 41
- 试验地点
- 11
- 主要终点
- Incidence of Dose Limiting Toxicities (DLT)
研究概览
简要总结
This is a multicenter, open label, three arms, Phase IB study.
A dose escalation phase of Temsirolimus (Torisel™) administered in intravenous (IV) at day 2, day 8 and day 15 in combination with three chemotherapies regimens for patients in relapsed/refractory Mantle Cell Lymphoma (MCL):
- Rituximab-Cyclophosphamide-Doxorubicin-Vincristine-Prednisone (R-CHOP) administered every 3 weeks for 6 cycles,
- Rituximab-Fludarabine-Cyclophosphamide (R-FC) administered every 4 weeks for 6 cycles,
- Rituximab-Aracytine high dose-Dexamethasone (R-DHA) administered every 4 weeks for 6 cycles.
详细描述
This is a three arms trial that investigates Temsirolimus (Torisel™) in combination with three chemotherapy regimens (R-CHOP, R-FC or R-DHA).
Primary Objective:
- To assess the feasibility of these three chemotherapy regimens in combination with Temsirolimus (Torisel™) and to assess the incidence of dose limiting toxicities (DLT) during the two first cycles of Temsirolimus (Torisel™) in combination with three chemotherapy regimens in order to determine the maximal tolerate dose (MTD) in a dose escalating study design in a population of patients in relapsed/refractory Mantle Cell Lymphoma (MCL).
Secondary objectives:
- To assess the safety of the association Temsirolimus with the three chemotherapy regimens,
- To determine the efficacy of the association of Temsirolimus (Torisel™) and these three chemotherapy regimens after 4 cycles and after 6 cycles at the end of treatment: response rate and complete response rate (CR), progression-free survival (PFS), response duration (RD) and overall survival (OS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically or cytologically confirmed refractory or relapsed Mantle Cell Lymphoma (at initial diagnosis or relapse),
- •Ann Arbor Stage I-IV with at least one tumor site measurable,
- •Patients who received prior therapy (at least one but no more than three lines therapies) for Mantle Cell Lymphoma (MCL),
- •Aged ≥ 18 years,
- •ECOG performance status 0, 1 or 2,
- •Adequate hepatic and renal function :
- •Serum Glutamic Oxaloacetic Transaminase (SGOT)/AST or Serum Glutamic Pyruvic TransaminaseSGPT/ALT ≤ 3.0 x upper limit of normal (ULN),
- •Serum Total Bilirubin ≤ 1.5 mg/dL (26 μmol/L) except in case of hemolytic anemia,
- •Serum Creatinine ≤ 2 mg/dL (177 μmol/L) or calculated Creatinine Clearance (Cock-croft-Gault formula) of ≥ 50 mL /min
- •Adequate bone marrow reserve :
- •Absolute neutrophil count (ANC) ≥ 1 G/L (1,000 cells/mm³)
- •Platelets count ≥ 50 G/L
- •Hemoglobin ≥ 9.0 g/dL,
- •Signed and date informed consent,
- •Life expectancy of ≥ 90 days (3 months)
排除标准
- •Other types of lymphomas, e.g. B-cell lymphoma,
- •Contraindication to any drug contained in the three chemotherapy regimens (R-CHOP, R-FC, R-DHA),
- •Tested positive for HIV,
- •Active Hepatitis B and/or C,
- •Exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited, to active systemic fungal infection, diagnosis of fever and neutropenia,
- •Any serious active disease or co-morbid medical condition (according to investigator's decision),
- •Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form,
- •Received a biological agent for anti-neoplastic intent within 30 days prior to the first dose of study drug,
- •Use of any standard or experimental anti-cancer drug therapy within 30 days prior to the first dose of study drug,
- •Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for ≥ 3 years,
- •Left Ventricular Ejection Fraction < 45% (calculated by echocardiographic or scintigraphic method),
- •Pregnancy or breast feeding women,
- •Women of childbearing potential who not willing to use an adequate method of birth controls for the duration of the study and for twelve months after the end of treatment,
- •Male patient whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for twelve months after the end of treatment.
研究组 & 干预措施
Torisel 15 mg
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 15 mg
干预措施: Torisel dose 15 mg and R-CHOP (Drug)
Torisel 15 mg
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 15 mg
干预措施: Torisel dose 15 mg and R-FC (Drug)
Torisel 15 mg
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 15 mg
干预措施: Torisel dose 15 mg and R-DHA (Drug)
Torisel 25 mg
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 25 mg
干预措施: Torisel dose 25 mg and R-CHOP (Drug)
Torisel 25 mg
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 25 mg
干预措施: Torisel dose 25 mg and R-FC (Drug)
Torisel 25 mg
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 25 mg
干预措施: Torisel dose 25 mg and R-DHA (Drug)
Torisel 50 mg
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 50 mg
干预措施: Torisel dose 50 mg and R-CHOP (Drug)
Torisel 50 mg
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 50 mg
干预措施: Torisel dose 50 mg and R-FC (Drug)
Torisel 50 mg
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 50 mg
干预措施: Torisel dose 50 mg and R-DHA (Drug)
Torisel 75 mg
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 75 mg
干预措施: Torisel dose 75 mg and R-CHOP (Drug)
Torisel 75 mg
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 75 mg
干预措施: Torisel dose 75 mg and R-FC (Drug)
Torisel 75 mg
Chemotherapy (R-CHOP, R-DHA or R-FC) associated to Torisel 75 mg
干预措施: Torisel 75 mg and R-DHA (Drug)
结局指标
主要结局
Incidence of Dose Limiting Toxicities (DLT)
时间窗: 56 days
The evaluable for DLT population is the subset of patients from all treated population with a DLT assessment at the two first cycles.
次要结局
- Overall Response at the end of treatment(28 days up to 42 days after the last treatment dose)
- Overall Survival (OS)(From the date of inclusion to the date of first documentated disease progression, relapse or death from any cause up to 3 years)
- Complete Response Rate(CR) after 4 cycles and at the end of treatment(28 days up to 42 days after the last treatment dose)
- Progression-free survival (PFS)(From the date of inclusion to the date of first documentated disease progression, relapse or death from any cause up to 3 years)
- Duration of Response(From the date of first documentation of a response to the date of first documented evidence of progression/relapse or death from any cause up to 3 years)
- Safety of association Temsirolimus with the three chemotherapy regimens(From the date of informed consent signature to 28 days after the last drug administration)