Randomised Controlled Open-label Study to Evaluate Efficacy & Safety of Intravenous Ferric Carboxymaltose Versus no Treatment in Anaemic Subjects With Multiple Myeloma & Iron Restricted Erythropoiesis Receiving Chemotherapy
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Change in haemoglobin (Hb) from baseline to Weeks 4, 6 and 8
研究概览
简要总结
Multicentre, randomised, controlled, 2-arm open-label prospective pilot study to evaluate efficacy and safety of ferric carboxymaltose (FCM) in treatment of anaemia in subjects with multiple myeloma (MM) initiating chemotherapy. The subjects will be screened for eligibility within 4 weeks prior to inclusion and randomised to receive intravenous infusions of FCM or standard care (the subjects may be treated according to the local institutional practice if requiring symptomatic management of anaemia). Thereafter the visits are scheduled at Weeks 0, 2, 4, 6 and 8.
详细描述
Patients will be randomised into two groups. One will receive active FCM treatment and the other group will receive local standard of care.
Active treatment group: Subjects will receive a total dose of 1,000 mg iron as FCM on the day of the first scheduled chemotherapy cycle or within 24 hours before or after receiving chemotherapy. In subjects of weight ≤66 kg, the first dose (500 mg) will be administered on the day of the first scheduled chemotherapy cycle and the second dose (500 mg) on the next study visit.
Standard of care group: Subjects will be treated according to the local institutional practice if requiring management of symptomatic anaemia. Intravenous iron should only be used to treat absolute iron deficiency (as defined as ferritin less than the lower limit of normal based on the test reference ranges). Patients with absolute iron deficiency are not eligible for inclusion to the study.
Rescue medication to manage anaemia is permitted in both arms at the discretion of the treating physician and/or per institutional practice.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Subjects (male or female) aged ≥18, suffering from a newly diagnosed or progressed/relapsed MM and scheduled to receive anti-myeloma treatment. Progression is defined according to "Uniform Response Criteria for Multiple Myeloma"
- •Subjects with progressed/relapsed MM should have had stable disease (during the last 6 months since prior treatment).
- •Life expectancy at least 6 months.
- •8.5 g/dL ≤Hb ≤11 g/dL at time of randomisation.
- •Iron-restricted erythropoiesis as defined:
- •Stainable iron in bone marrow (BM) combined with transferrin saturation (TSAT) ≤20%, or
- •where the evaluation of stainable iron in BM is not possible or available:
- •ferritin >30 ng/mL (women) or >40 ng/mL (men), and
- •TSAT ≤20%
- •Females of child-bearing potential must have a negative urine pregnancy test at screening.
- •Before any study-specific procedure, the appropriate written informed consent must be obtained.
排除标准
- •Any anaemia treatment within 4 weeks prior to randomisation (including red blood cell transfusions, treatment with ESA or any oral/parenteral iron preparations).
- •Anthracycline containing chemotherapy regimens.
- •Subjects weighing <35 kg.
- •Folate deficiency (serum-folate <4.5 nmol/L) and/or Vitamin B12 deficiency (serum-cobalamin <145 pmol/L).
- •Ongoing haemolysis defined as serum-haptoglobin <0.2 g/L.
- •Known chronic renal failure, glomerular filtration rate <30 mL/min/m
- •Recent (within last 4 weeks) significant bleeding/surgery, defined as drop in Hb of ≥2 g/dL.
- •Clinically relevant active inflammatory disease other than MM (according to the judgement of the Investigator).
- •Clinically relevant ongoing infectious disease including known human immunodeficiency virus.
- •Serum ferritin >600 ng/mL.
- •Ongoing significant neurological or psychiatric disorders including psychotic disorders or dementia.
- •Significant cardiovascular disease prior to study inclusion including myocardial infarction within 12 months prior to study inclusion, congestive heart failure New York Heart Association Grade III or IV, or poorly controlled hypertension according to the judgment of the Investigator.
- •Elevation of liver enzymes (aspartate aminotransferase, alanine aminotransferase) over 3 times above the normal range or known acute hepatic disorder.
- •Subject currently is enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(ies), or subject is receiving other investigational agent(s).
- •Subject of child-bearing potential is evidently pregnant (e.g., positive human chorionic gonadotropin test) or is breast feeding.
- •Subject is not using adequate contraceptive precautions. Adequate contraceptive precautions are defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intra-uterine devices, sexual abstinence or vasectomised partner. Non-childbearing potential includes being surgically sterilised at least 6 months prior to the study or post-menopausal, defined as amenorrhea for at least 12 months.
- •Subject has known sensitivity to any of the products to be administered during dosing.
- •Subject will not be available for follow-up assessment.
- •Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
研究组 & 干预措施
Ferric carboxymaltose
Subjects will receive a total dose of 1,000 mg iron as FCM on the day of the next scheduled chemotherapy cycle after randomisation or continuous chemotherapy. In subjects with weight ≤66 kg, the first dose iron will be 500 mg; the second dose (500 mg) will be administered on the visit 3 (week 2).
干预措施: Ferric carboxymaltose (Drug)
结局指标
主要结局
Change in haemoglobin (Hb) from baseline to Weeks 4, 6 and 8
时间窗: week 4, 6 and 8 post baseline
Mean change in Hb from baseline to Weeks 4, 6 and 8 (end of treatment) in the absence of any red cell transfusion or erythropoiesis stimulating agents (ESA) treatment.
次要结局
- Subjects receiving red blood cell transfusions or subjects treated with ESA(Baseline until end of study (week 8))
- Adverse events(Baseline until end of study (week 8))
- Percentage of subjects with a blood Hb correction to at least 12 g/dL(12 weeks post baseline)
- Time to Hb response defined as increase in Hb equal to or more than 1 g/dL(Baseline until end of study (week 8))
- Change in transferrin saturation (TSAT) from baseline to Weeks 2, 4, 6 and 8(week 2, 4, 6, and 8 post baseline)
- Transfusion/treatment with ESA(Baseline until end of study (week 8))
- Change in serum ferritin from baseline to Weeks 2, 4, 6 and 8(week 2, 4, 6, and 8 post baseline)
- Percentage of subjects with blood Hb response of at least 1 g/dL(12 weeks post baseline)
- Change in serum iron from baseline to Weeks 2, 4, 6 and 8(week 2, 4, 6, and 8 post baseline)
- Change in blood reticulocyte haemoglobin content/red blood cell size factor from baseline to Weeks 2, 4, 6 and 8(week 2, 4, 6, and 8 post baseline)
- Change in hepcidin from baseline to Weeks 2, 4, 6 and 8(week 2, 4, 6, and 8 post baseline)
- Change in interleukin-6 from baseline to Weeks 2, 4, 6 and 8(week 2, 4, 6, and 8 post baseline)
- Change in endogenous erythropoietin from baseline to Weeks 2, 4, 6 and 8(week 2, 4, 6, and 8 post baseline)
- Change in percentage of hypochromic red cells/percentage of low Hb density from baseline to Weeks 2, 4, 6 and 8(week 2, 4, 6, and 8 post baseline)