EUCTR2011-000609-32-GB进行中（未招募）不适用
A Multicenter, Phase 1-2 Study of MLN8237, an Oral Aurora A Kinase Inhibitor, in Patients With Relapsed or Refractory Aggressive B-Cell Lymphoma Treated With Rituximab and Vincristine
适应症
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 100
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •1. Patients must have histologically confirmed diagnosis of DLBCL/TFL (WHO criteria, with neoplastic cells expressing CD20). Transformed DLBCL/TFL from a previous indolent NHL or the concomitant presence of a component of low-grade lymphoma will not exclude participation. (Note: Patients with Mantle cell or Burkitt’s lymphoma) may be eligible for enrollment to the safety lead-in and dose escalation cohorts, parts 1 and 2 only.
- •2. Relapsed or refractory after at least 1 prior systemic treatment for aggressive lymphoma (including anthracycline unless contra-indicated). Relapsed is defined as patients who initially responded and then progressed. Refractory is defined as patients who, in the judgment of the investigator, received adequate prior treatment and did not respond during treatment or progressed within 60 days of last treatment. Relapse following an autologous stem cell transplant is allowed.
- •3. Patients must have relapsed after autologous stem cell transplantation or not be eligible for autologous stem cell transplantation, in the judgment of the investigator, or refuse autologous stem cell transplantation. Patients may have received up to 4 treatment regimens for aggressive lymphoma. Salvage chemotherapy and high-dose conditioning for autologous stem cell transplantation count as 2 separate regimens. Patients enrolled to the phase 2 part must have received prior rituximab.
- •4. Measurable disease on cross-sectional imaging that is at least 2.0 cm in the longest diameter.
- •5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- •6. Male or female patients 18 years or older.
- •7. Female patients who:
- •Are postmenopausal for at least 1 year before the screening visit, or
- •Are surgically sterile, or
- •If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing of the informed consent form (ICF) through 30 days after the last dose of MLN8237 or agree to completely abstain from heterosexual intercourse. Individuals of childbearing potential should also use effective contraception for 12 months following the last dose of rituximab.
- •8. Male patients, even if surgically sterilized (ie, status postvasectomy), who:
- •Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of MLN8237, or
- •Agree to completely abstain from heterosexual intercourse.
- •9. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
- •Are the trial subjects under 18? no
- •Number of subjects for this age range: 0
- •F.1.2 Adults (18-64 years) yes
- •F.1.2.1 Number of subjects for this age range 60
- •F.1.3 Elderly (>=65 years) yes
- •F.1.3.1 Number of subjects for this age range 40
- •1. Patients must have histologically confirmed diagnosis of DLBCL/TFL (WHO criteria, with neoplastic cells expressing CD20). Transformed DLBCL/TFL from a previous indolent NHL or the concomitant presence of a component of low-grade lymphoma will not exclude participation. (Note: Patients with Mantle cell or Burkitt’s lymphoma) may be eligible for enrollment to the safety lead-in and dose escalation cohorts, parts 1 and 2 only.
- •2. Relapsed or refractory after at least 1 prior systemic treatment for aggressive lymphoma (including anthracycline unless contra-indicated). Relapsed is defined as patients who initially responded and then progressed. Refractory is defined as patients who, in the judgment of the investigator, received adequate prior treatment and did not respond during treatment or progressed within 60 days of last treatment. Relapse following an autologous stem cell transplant is allowed.
- •3. Patients must have relapsed after autologous stem cell transplantation or not be eligible for autologous stem cell transplantation, in the judgment of the investigator, or refuse autologous stem cell transplantation. Patients may have received up to 4 treatment regimens for aggressive lymphoma. Salvage chemotherapy and high-dose conditioning for autologous stem cell transplantation count as 2 separate regimens. Patients enrolled to the phase 2 part must have received prior rituximab.
- •4. Measurable disease on cross-sectional imaging that is at least 2.0 cm in the longest diameter.
- •5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- •6. Male or female patients 18 years or older.
- •7. Female patients who:
- •Are postmenopausal for at least 1 year before the screening visit, or
- •Are surgically sterile, or
- •If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing of the informed consent form (ICF) through 30 days after the last dose of MLN8237 or agree to completely abstain from heterosexual intercourse. Individuals of childbearing potential should also use effective contraception for 12 months following the last dose of rituximab.
- •8. Male patients, even if surgically sterilized (ie, status postvasectomy), who:
- •Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of MLN8237, or
- •Agree to completely abstain from heterosexual intercourse.
- •9. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
- •Are the trial subjects under 18? no
- •Number of subjects for this age range: 0
- •F.1.2 Adults (18-64 years) yes
- •F.1.2.1 Number of subjects for this age range 60
- •F.1.3 Elderly (>=65 years) yes
- •F.1.3.1 Number of subjects for this age range 40
排除标准
- •1. Received more than 4 prior systemic treatment regimens for lymphoma
- •2. Known seropositive for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness; HBV, or hepatitis C virus (HCV); known history of Charcot-Marie-Tooth disease or polio
- •3. Diagnosed or treated for a malignancy other than lymphoma within 2 years prior to first dose, or evidence of active malignancy other than lymphoma. Patients are not excluded if they have basal cell or squamous cell carcinoma of the skin that was completely resected or any in situ malignancy that was adequately treated.
- •4. Clinical laboratory values as specified below:
- •Total serum bilirubin > 1.5 x the upper limit of normal (ULN).
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 3.0 x the ULN. AST and ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to documented liver involvement bylymphoma
- •Absolute neutrophil count (ANC) < 1,250/mm3 without growth factor support
- •Platelet count < 75,000/mm3 without growth factor or transfusion support
- •Calculated creatinine clearance < 30 mL/minute (see Cockcroft-Gault formula in protocol)
- •5. Autologous stem cell transplant less than 3 months prior to enrollment
- •6. Patients who have undergone allogeneic stem cell or organ transplantation any time
- •7. Systemic antineoplastic therapy, including glucocorticoids (> 15 mg prednisone/day or equivalent) or treatment with an investigational agent within 14 days preceding the first dose of study drug treatment (see Section in protocol). No concurrent systemic corticosteroids are allowed except for treatment of anaphylactic-like reactions to study drugs. Steroids are permitted for administration with rituximab to prevent or treat infusion reaction
- •8. Patients who have received treatment with nitrosoureas, mitomycin C, rituximab, alemtuzumab, or other unconjugated antibody treatment within 42 days (21 days if clear evidence of PD) prior to the first day of study drug treatment
- •9. Patients who have received treatment with radioimmunoconjugates or toxin immunoconjugates, such as ibritumomab-tiuxetan, or tositumomab, within 12 weeks prior to the first day of study drug treatment
- •10. Patients who have received radiotherapy within 21 days prior to the first day of study drug treatment
- •11. Patients treated with enzyme-inducing antiepileptic drugs, such as phenytoin, carbamazepine, or phenobarbital, or with rifampin, rifabutin, rifapentine, or St. John’s wort, within 14 days prior to the first dose of MLN8237; co-administration of these drugs is also not permitted during participation in the study
- •12. Myocardial infarction within 6 months of enrollment or current history of New York Heart Association (NYHA) Class III or IV heart failure (see Section in protocol), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia (heart disease)
- •13. Has an LVEF measured by MUGA or echocardiogram of < 40%
- •14. Major surgery within 14 days prior to the first dose of study treatment
- •15. Infection requiring systemic antibiotic therapy within 14 days prior to the first dose of study treatment, or other serious infection
- •16. History of hemorrhagic or thrombotic cerebrovascular event in the past 12 months
- •17. Clinically uncontrolled CNS involvement. Patients who have a history of CNS involvement but no evidence of active CNS disease are not exclud;
- •1. Received more than 4 prior systemic treatment regimens for lymphoma
- •2. Known seropositive for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness; HBV, or hepatitis C virus (HCV); known history of Charcot-Marie-Tooth disease or polio
- •3. Diagnosed or treated for a malignancy other than lymphoma within 2 years prior to first dose, or evidence of active malignancy other than lymphoma. Patients are not excluded if they have basal cell or squamous cell carcinoma of the skin that was completely resected or any in situ malignancy that was adequately treated.
- •4. Clinical laboratory values as specified below:
- •Total serum bilirubin > 1.5 x the upper limit of normal (ULN).
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 3.0 x the ULN. AST and ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to documented liver involvement bylymphoma
- •Absolute neutrophil count (ANC) < 1,250/mm3 without growth factor support
- •Platelet count < 75,000/mm3 without growth factor or transfusion support
- •Calculated creatinine clearance < 30 mL/minute (see Cockcroft-Gault formula in protocol)
- •5. Autologous stem cell transplant less than 3 months prior to enrollment
- •6. Patients who have undergone allogeneic stem cell or organ transplantation any time
- •7. Systemic antineoplastic therapy, including glucocorticoids (> 15 mg prednisone/day or equivalent) or treatment with an investigational agent within 14 days preceding the first dose of study drug treatment (see Section in protocol). No concurrent systemic corticosteroids are allowed except for treatment of anaphylactic-like reactions to study drugs. Steroids are permitted for administration with rituximab to prevent or treat infusion reaction
- •8. Patients who have received treatment with nitrosoureas, mitomycin C, rituximab, alemtuzumab, or other unconjugated antibody treatment within 42 days (21 days if clear evidence of PD) prior to the first day of study drug treatment
- •9. Patients who have received treatment with radioimmunoconjugates or toxin immunoconjugates, such as ibritumomab-tiuxetan, or tositumomab, within 12 weeks prior to the first day of study drug treatment
- •10. Patients who have received radiotherapy within 21 days prior to the first day of study drug treatment
- •11. Patients treated with enzyme-inducing antiepileptic drugs, such as phenytoin, carbamazepine, or phenobarbital, or with rifampin, rifabutin, rifapentine, or St. John’s wort, within 14 days prior to the first dose of MLN8237; co-administration of these drugs is also not permitted during participation in the study
- •12. Myocardial infarction within 6 months of enrollment or current history of New York Heart Association (NYHA) Class III or IV heart failure (see Section in protocol), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia (heart disease)
- •13. Has an LVEF measured by MUGA or echocardiogram of < 40%
- •14. Major surgery within 14 days prior to the first dose of study treatment
- •15. Infection requiring systemic antibiotic therapy within 14 days prior to the first dose of study treatment, or other serious infection
- •16. History of hemorrhagic or thrombotic cerebrovascular event in the past 12 months
- •17. Clinically uncontrolled CNS involvement. Patients who have a history of CNS involvement but no evidence of active CNS disease are not exclud
研究者
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