NCT06075706进行中（未招募）2 期
A Randomised, Open-label, Controlled, Multicentre, Phase 2 Trial of First-line Treatment With Mesenchymal Stromal Cells MC0518 Versus Best Available Therapy in Paediatric Participants With Steroid-refractory Acute Graft-versus-host Disease After Allogeneic Stem Cell Transplantation (BALDER Trial)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- medac GmbH
- 入组人数
- 49
- 试验地点
- 41
- 主要终点
- Number of Participants With Overall Response (OR)
研究概览
简要总结
The purpose of this trial is the comparative evaluation of overall response rate (ORR) in paediatric participants with steroid-refractory acute graft-versus-host disease (SR-aGvHD) at Visit Day 28 after treatment with MC0518 or first used best available therapy (BAT).
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
- 28 Days 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant had a previous allogeneic HSCT as indicated for non-malignant (including inborn errors of metabolism, primary immunodeficiencies, haemoglobinopathies, and bone marrow failure syndromes) or hematological malignant disease or neuroblastoma.
- •Participant has been clinically diagnosed with Grade II to IV aGvHD according to Harris et al. A biopsy of the involved organs with aGvHD is encouraged but not required.
- •Participant has experienced failure of previous first-line aGvHD treatment (that is, SR-aGvHD), defined as:
- •aGvHD progression within 3 to 5 days of therapy onset with >=2 milligram per kilogram per day (mg/kg/day) of prednisone equivalent or
- •failure to improve within 5 to 7 days of treatment initiation with >=2 mg/kg/day of prednisone equivalent or
- •incomplete response after greater than (>) 28 days of immunosuppressive treatment including at least 5 days with >=2 mg/kg/day of prednisone equivalent.
- •Male or female participant who is >=28 days and <18 years of age and has a minimum body weight of 3.2 kilograms (kg) at the Screening Visit.
- •Participant has an estimated life expectancy of >28 days.
- •Participant, if female and of childbearing potential, agrees to use a highly effective contraceptive measure starting at the Screening Visit and continuing throughout the entire trial period.
- •Participant, if a fertile male, agrees to sexual abstinence or to use a condom during sexual activity with their female partner of childbearing potential or pregnant partner. Additionally, if their partner is a woman of childbearing potential (WOCBP), then their partner must use an additional highly effective contraceptive method during sexual activity starting at the Screening Visit and continuing throughout the entire trial period.
- •A written informed consent of the participant's parent(s) / legal guardian(s) (and participant's assent, when applicable) has been obtained according to national regulations.
排除标准
- •Participant has overt relapse or progression or persistence of the underlying disease.
- •Participant has received the last HSCT for a solid tumor disease other than neuroblastoma.
- •Participant has graft-versus-host disease overlap syndrome.
- •Participant has received systemic first-line treatment for aGvHD other than steroids and a prophylaxis with other than calcineurin inhibitors, mammalian target of rapamycin (mTOR) inhibitors, anti-thymocyte globulin, mycophenolate mofetil, methotrexate, abatacept, or cyclophosphamide. Note: In vitro or in vivo graft manipulation to prevent graft-versus-host disease (example, T-cell depletion) during HSCT is permitted. Restart of initial prophylaxis with calcineurin inhibitors, mammalian target of rapamycin inhibitors, or mycophenolate mofetil after aGvHD onset is permitted.
- •Participant has received prior mesenchymal stromal cell (MSC) treatment, including MC0518/Obnitix®.
- •Participant has a known pregnancy (as confirmed by a positive pregnancy test result at the Screening Visit) and / or is breastfeeding.
- •Participant has a known hypersensitivity to MC0518 and / or its excipients (dimethyl sulfoxide, human serum albumin, isotonic sodium chloride solution).
- •Participant has a known hypersensitivity or any contraindication to the Investigator's choice BAT (extracorporeal photopheresis, anti thymocyte globulin, etanercept, infliximab, or ruxolitinib) and / or its excipients. For a list of excipients please refer to the respective Summary of Product Characteristics.
- •Participant has an underlying or current medical or psychiatric condition that, in the opinion of the Investigator, would interfere with the evaluation of the participant.
- •Participant has an uncontrolled infection (examples, sepsis or multi-organ failure) including significant bacterial, fungal, viral, or parasitic infection requiring treatment.
- •Participant has received treatment with any other investigational agent within 30 days or 5 half-lives (whichever is longer) before the Screening Visit.
研究组 & 干预措施
Best Available Therapy (BAT)
Active Comparator
Participants will receive one of the following systemic BATs based on the Investigator's decision: extracorporeal photopheresis (ECP), anti-thymocyte globulin (ATG), etanercept, infliximab or ruxolitinib (RUX).
干预措施: BAT (Biological)
MC0518
Experimental
Participants will be treated with intravenous infusions of MC0518 at a dose of 1 to 2*10^6 cells per kilogram (cells/kg) (based on body weight at the Screening Visit). Infusions will be administered once a week for 4 weeks (Visit Day 1, 8, 15, and 22). Participants with partial response (PR) on Day 28 will have 2 additional MC0518 infusions administered on Day 29 and 36.
干预措施: MC0518 (Biological)
结局指标
主要结局
Number of Participants With Overall Response (OR)
时间窗: At Day 28
OR is defined as complete response (CR) or partial response (PR) at Day 28 relative to acute graft-versus-host disease (aGvHD) status at baseline. CR is defined as resolution of aGvHD in all involved organs. PR is defined as improvement in 1 stage in at least 1 or more organs involved with aGvHD symptoms without progression in others.
次要结局
- Number of Participants With Graft Failure (GF)(Baseline up to Month 24)
- Change From Baseline in aGvHD Grades(Baseline, Days 8, 15, 22, 28, 60, 100 and 180)
- Time to Response(From the date of the first treatment administration to the date of the first response (CR or PR) (up to 5 years))
- Number of Participants With aGvHD Response(At Days 28, 60, 100 and 180)
- Number of Participants With Relapse or Progression in Participants With Underlying Malignant Disease(From randomization up to Month 24)
- Time to Relapse or Progression in Participants With Underlying Malignant Disease(From randomization up to Month 24)
- Change From Baseline in Performance Score Based on Lansky Scale(Baseline, Days 8, 15, 22, 28, 60 and 100)
- Number of Participants With Freedom From Treatment Failure (FFTF) Until 6 Months (Day 180)(Up to 6 months (Day 180))
- Overall Survival (OS)(Up to Month 24)
- Duration of Response(Up to Month 24)
- Number of Participants With Best Overall Response (OR)(Up to Day 28)
- Cumulative Dose of Steroids for SR-aGvHD per Kilogram (kg) of Body Weight(From the date of the first treatment administration up to Day 28, Day 60, and Month 24)
- Number of Participants With Chronic Graft-versus-host Disease (cGvHD)(From Day 60 up to Month 24)
- Time to Chronic Graft-versus-host Disease (cGvHD)(From Day 60 up to Month 24)
- Non-relapse Mortality (NRM)(From the date of randomization to the date of death without previous relapse or progression of the underlying disease (up to Month 24))
- Change From Baseline in Performance Score Based on Karnofsky Scale(Baseline, Days 8, 15, 22, 28, 60 and 100)
- Event-free Survival (EFS)(From the date of randomization to date of GF, relapse or progression of the underlying disease, or death due to any cause, whichever occurs first (up to Month 24))
- Number of Participants With Adverse Events (AEs)(Up to Month 24)
- Number of Participants With Adverse Reactions (ARs) by Severity(Up to Month 24)
- Pediatric Quality of Life Inventory (PedsQL™) 4.0 Generic Core Scale Score(Baseline, Days 28, 60, 100 and 180)
- Change From Baseline in PedsQL™ Stem Cell Transplant Module Scale Score(Baseline, Days 28, 60, 100 and 180)
研究者
研究点 (41)
Loading locations...
相似试验
已完成
2 期
Study of Ipilimumab (MDX-010) Monotherapy in Patients With Previously Treated Unresectable Stage III or IV MelanomaMelanomaNCT00289640Bristol-Myers Squibb210
终止
2 期
Efficacy and Safety of Imatinib Mesylate Plus Hydroxyurea (HU) in Patients With Recurrent Glioblastoma Multiforme (GBM)Recurrent Glioblastoma Multiforme (GBM)NCT00290771Novartis231
终止
4 期
Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory SeizuresEpilepsyNCT01118455Cyberonics, Inc.134
终止
2 期
Phase II Study to Evaluate Overall Response in Patients With Higher Risk Myelodysplastic Syndromes (MDS) Treated With Azacitidine With or Without Deferasirox.High Risk MDSNCT02159040Novartis Pharmaceuticals1
进行中（未招募）
3 期
Comparing the Efficacy and Safety of a New Additional Treatment With Tislelizumab in Non-Small Cell Lung Cancer (NSCLC)NCT04379635BeiGene453