Pre-emptive Daratumumab Therapy of Minimal Residual Disease Reappearance or Biochemical Relapse in Multiple Myeloma
赞助:
Polish Myeloma Consortium
合作者:
信息的提供 (责任方):
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| 追踪信息 | |||
|---|---|---|---|
| 首次提交日期 ICMJE | September 20, 2018 | ||
| 首次发布日期e ICMJE | October 5, 2018 | ||
| 最后更新发布日期 | October 5, 2018 | ||
| 预计研究开始日期 ICMJE | October 2018 | ||
| 预计主要完成日期 | September 2020 (主要结果测量的最终数据收集日期) | ||
| 目前主要观察指标 ICMJE |
Event Free Survival (ESF)[ Time Frame: from randomization till the date of development clinical relapse or death from any cause; up to 129 weeks ] To compare (EFS) between daratumumab arm and observation arm after randomization of patients with biochemical relapse of Multiple Myeloma and MRD reappearance in Multiple Myeloma |
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| 原始主要观察测量 ICMJE | 与当前相同 | ||
| 目前的二级观察 ICMJE |
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| 描述性信息 | |||
| 简略标题 ICMJE | Pre-emptive Daratumumab Therapy of Minimal Residual Disease Reappearance or Biochemical Relapse in Multiple Myeloma | ||
| 正式标题 ICMJE | Pre-emptive Daratumumab Therapy of Minimal Residual Disease Reappearance or Biochemical Relapse in Multiple Myeloma (PREDATOR) | ||
| 简要概况 | PREDATOR is a study investigating a role of preemptive daratumumab therapy for preclinical relapse or progression of multiple myeloma (MM). |
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| 详细说明 | The study is composed of two phase 2 randomized multi-center substudies: - PREDATOR-BR: to investigate the role of daratumumab in the setting of biochemical relapse - PREDATOR-MRD: to investigate the role of daratumumab in minimal residual disease (MRD) reappearance | ||
| 研究类型 ICMJE | Interventional | ||
| 研究阶段 | Phase 2 | ||
| 研究设计 ICMJE | 分配: Randomized 干预模型: Parallel Assignment 干预模型描述: treatment arm and control (observation) arm 盲法: Interventional 盲法描述: 主要目的: Prevention |
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| 适用条件 ICMJE | |||
| 干预项目 ICMJE |
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| 研究工具 |
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| 招募信息 | |||
| 招募状态 ICMJE | Not yet recruiting | ||
| 预计入组 ICMJE |
274 | ||
| 原始预计入组 ICMJE | 与当前相同 | ||
| 预计研究完成日期 | July 2024 | ||
| 预计主要完成日期 | September 2020 (主要结果测量的最终数据收集日期) | ||
| 合格标准 ICMJE | PREDATOR-BR: Inclusion Criteria: 1. Patients with diagnosed symptomatic MM who have completed one or two prior lines of therapy; single or tandem autologous stem cell transplant is not considered a separate line of therapy and is not mandatory; and have achieved at least PR to last line of therapy, and who experience asymptomatic biochemical progression not meeting criteria for SPR. 2. Males and females ≥18 years of age. 3. Life expectancy of more than 3 months. 4. ECOG performance status of 0-2. 5. Adequate hepatic function, with bilirubin ≤1.5 x ULN and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN. 6. ANC ≥1.0 x 109/L, hemoglobin ≥8 g/dL, platelet count ≥75 x 109/L. 7. Calculated creatinine clearance (by Cockroft-Gault) ≥50 mL/min (this equation is as follows: Creatinine clearance in ml/min: (140 - age) x body weight (kg) / 72 x plasma creatinine (mg/dL); multiplied by 0.85 for women) or serum creatinine below 2 g/dL. 8. Negative pregnancy test (serum βHCG) for women of childbearing potential (including pre-menopausal women who have had a tubal ligation) and for all women not meeting the definition of postmenopausal (≥ 24 months of amenorrhea), and who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy. For all other women, documentation must be present in medical history confirming that the patient is not of childbearing potential. 9. FCBP must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the study. 10. 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 28 days following discontinuation from the study even if he has undergone a successful vasectomy. 11. Voluntary written informed consent. Exclusion Criteria: 1. Potential subjects with evidence of progressive disease (CRAB symptoms) as per IMWG criteria. 2. Patient with SPR - significant paraprotein relapse defined as doubling of the M-component in two consecutive measurements separated by < 2 months; or an increase in the absolute levels of serum M protein by 1g/dl, or urine M protein by 500mg /24h, or involved serum FLC level by 20mg/dl (plus an abnormal FLC ratio) in two consecutive measurements separated by < 2 months. 3. Patients who have already started or received post-transplant maintenance or consolidation treatment. 4. Subject has received daratumumab or other anti-CD38 therapies previously. 5. Patients not able to tolerate daratumumab or required concomitant medication and procedures. 6. Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal. Note that FEV1 testing is required for subjects suspected of having COPD and subjects must be excluded if FEV1 <50% of predicted normal. 7. Known moderate or severe persistent asthma, or a history of asthma within the last 2 years, or currently has uncontrolled asthma of any classification. (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study). 8. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes). 9. Plasma cell leukemia. 10. Waldenström's macroglobulinemia. 11. CNS involvement. 12. Pregnant or lactating females. 13. Radiotherapy within 14 days before randomization. Seven days may be considered if to single area. 14. Major surgery within 3 weeks prior to first dose. Kyfoplasty is not considered as a major surgery. 15. Myocardial infarction within 3 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. 16. Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead ECG during screening. 17. Patient who in investigator's opinion is unable to comply with the protocol requirements. 18. Uncontrolled hypertension or diabetes. 19. Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to enter the study. 20. Active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible. 21. Non-hematologic malignancy or non-myeloma hematologic malignancy within the past 3 years except a) adequately treated basal cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, or prostate cancer < Gleason Grade 6 with stable prostate specific antigen levels or cancer considered cured by surgical resection alone. 22. Any clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent. PREDATOR-MRD: Inclusion Criteria: 1. Patients with diagnosed symptomatic MM who have completed one or two prior lines of therapy; single or tandem autologous stem cell transplant is not considered a separate line of therapy and is not mandatory; and have achieved CR with negative MRD to the last line of therapy and who remain in CR MRD negative. The last response assessment confirming CR MRD negative status based on assessment of bone marrow sample using flow cytometry with sensitivity of at least 10-5 needs to be performed not earlier than 3 months before inclusion to the study. 2. Males and females ≥18 years of age. 3. Life expectancy of more than 3 months. 4. ECOG performance status of 0-2. 5. Adequate hepatic function, with bilirubin ≤1.5 x ULN and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN. 6. ANC ≥1.0 x 109/L, hemoglobin ≥8 g/dL, platelet count ≥75 x 109/L. 7. Calculated creatinine clearance (by Cockroft-Gault) ≥50 mL/min (this equation is as follows: Creatinine clearance in ml/min: (140 - age) x body weight (kg) / 72 x plasma creatinine (mg/dL); multiplied by 0.85 for women) or serum creatinine below 2 g/dL. 8. Negative pregnancy test (serum βHCG) for women of childbearing potential (including pre-menopausal women who have had a tubal ligation) and for all women not meeting the definition of postmenopausal (≥ 24 months of amenorrhea), and who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy. For all other women, documentation must be present in medical history confirming that the patient is not of childbearing potential 9. FCBP must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the study. 10. 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 28 days following discontinuation from the study even if he has undergone a successful vasectomy. 11. Voluntary written informed consent. Exclusion criteria: 1. Potential subjects with evidence of progressive disease (CRAB symptoms) as per IMWG criteria. 2. Patient with SPR - significant paraprotein relapse defined as doubling of the M-component in two consecutive measurements separated by < 2 months; or an increase in the absolute levels of serum M protein by 1g/dl, or urine M protein by 500mg /24h, or involved serum FLC level by 20mg/dl (plus an abnormal FLC ratio) in two consecutive measurements separated by < 2 months. 3. Patients who have already started or received post-transplant maintenance or consolidation treatment. 4. Subject has received daratumumab or other anti-CD38 therapies previously. 5. Patients not able to tolerate daratumumab or required concomitant medication and procedures. 6. Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal. Note that FEV1 testing is required for subjects suspected of having COPD and subjects must be excluded if FEV1 <50% of predicted normal. 7. Known moderate or severe persistent asthma, or a history of asthma within the last 2 years, or currently has uncontrolled asthma of any classification. (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study). 8. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes). 9. Plasma cell leukemia. 10. Waldenström's macroglobulinemia. 11. CNS involvement. 12. Pregnant or lactating females. 13. Radiotherapy within 14 days before randomization. Seven days may be considered if to single area. 14. Major surgery within 3 weeks prior to first dose. Kyfoplasty is not considered as a major surgery. 15. Myocardial infarction within 3 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. 16. Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12- lead ECG during screening. 17. Patient who in investigator's opinion is unable to comply with the protocol requirements. 18. Uncontrolled hypertension or diabetes. 19. Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to enter the study. 20. Active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible. 21. Non-hematologic malignancy or non-myeloma hematologic malignancy within the past 3 years except a) adequately treated basal cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, or prostate cancer < Gleason Grade 6 with stable prostate specific antigen levels or cancer considered cured by surgical resection alone. 22. Any clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent. | ||
| 性别 |
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| 年龄 | 最小年龄：18 Years ，最大年龄：N/A | ||
| 接受健康的志愿者 | 没有 | ||
| 可入组国家 ICMJE | Poland | ||
| 管理信息 | 数据检测委员会 | No | |
| 研究涉及美国FDA监管的产品 |
研究美国FDA监管的药品: No 研究涉及美国FDA监管的设备产品: No |
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| IPD 共享声明 |
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| 责任方 | ， | ||
| 研究赞助商 ICMJE | Polish Myeloma Consortium | ||
| 合作者 ICMJE | |||
| 研究员 ICMJE |
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| PRS 账户 | |||
| 验证日期 | October 2018 | ||
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ICMJE 国际医学期刊编辑委员会和 世界卫生组织 ICTRP 要求的元素 |
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