Evaluating the Feasibility of an Intensity-Adapted Pediatric Acute Myeloid Leukemia Treatment Guideline in Malawi
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Determine the implementation success of an intensity adapted clinical practice guideline (CPG) based upon recommendations by the International Society of Paediatric Oncology (SIOP) for childhood AML in resource limited settings.
研究概览
简要总结
In resource-constrained settings such as Malawi, survival rates for pediatric acute myeloid leukemia (AML) are dismally low compared to high-resource environments. This disparity highlights the urgent need for feasible treatment protocols tailored to the realities of these regions where most children with cancer are treated. In 2023, after reviewing favorable clinical trials results in other resource-limited settings, the Kamuzu Central Hospital (KCH) pediatric cancer unit adopted an evidence-based intensity-adapted clinical practice guideline (CPG) developed by the International Society of Paediatric Oncology (SIOP) as its standard of care for the treatment of pediatric AML, aiming to balance curative intent with manageable toxicity. The current study is a prospective evaluation of outcomes of standard of care in Malawi using the SIOP CPG in a real-world setting.
The LEAP study aims to assess the implementation of the SIOP AML guidelines at KCH in an effort to continually improve outcomes in Malawi. The study is an observational-implementation design with a composite effectiveness-implementation outcome called Implementation Success. Implementation Success combines feasibility, the ability of patients to complete all aspects of the CPG, with effectiveness, the ability to maintain historical rates of complete remission of 40% at the treatment center.
This prospective cohort study will enroll children under 18 years diagnosed with de novo AML at KCH. Implementation Success will be the primary endpoint, with secondary endpoints including CPG fidelity, long-term survival, adverse events, and hematologic recovery times. Patient-reported outcomes will also be collected to assess the impact of treatment on quality of life.
This will be the first prospective study of pediatric AML in sub-Saharan Africa, providing critical data on the management of AML in low-resource settings. By assessing the implementation of a context-adapted CPG, the study will contribute to the global effort to improve pediatric AML outcomes in resource-constrained environments. The findings will serve to guide practitioners in Malawi and similar settings, and the data generated will be invaluable for future clinical decisions and CPG development.
详细描述
Participants:
- All patients with have de novo AML presenting to Kamuzu Central Hospital (KCH) in Lilongwe, Malawi will be offered enrollment into the study.
- Patients must be <18 years of age at time of study enrollment.
- Patients must begin treatment according to the 2023 KCH AML therapy CPG.
- All patients at the treating center receiving curative-intent therapy for AML are treated on the 2023 KCH AML standard of care CPG based on the SIOP AML guidelines, independent of participation in research.
- Patients should ideally be consented for data collection within one week of confirmatory diagnosis to ensure highest quality of prospective data collection.
The therapy guideline used at KCH is based upon the published international guidelines for treating pediatric AML in resource-constrained centers published by the International Society of Paediatric Oncology (SIOP). It is currently the standard of care at KCH.
Data Collection Schedule:
All study measurements in this study are routinely captured as part of clinical care. No additional clinical studies will be obtained from patients as a consequence of enrollment onto the LEAP study.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age Patients must be <18 years of age at time of study enrollment.
- •Patients must be diagnosed with de novo AML according to 2022 WHO 5th Edition classification with or without extramedullary disease. Patients must have one of the following:
- •Bone marrow myeloblasts ≥20%. In cases of dry taps due to fibrosis, myeloblast percentage can be estimated from a bone marrow biopsy core specimen. Due to unavailable molecular/cytogenetic diagnostics in Malawi, patients with <20% bone marrow myeloblasts can be included in the study at the discretion of the treating oncologist with rationale documented.
- •In cases where a bone marrow evaluation is not safe/feasible, a peripheral blood sample may be used with a documented absolute myeloblast percentage of ≥1000/μL calculated based on a total white blood cell count and percentage circulating blasts.
- •Therapy Patients must begin treatment according to the 2023 KCH AML therapy CPG.
排除标准
- •Patients with any of the following conditions or criteria will be excluded from the study:
- •Juvenile myelomonocytic leukemia
- •Transient myeloproliferative disorder
- •Acute promyelocytic leukemia
- •Mixed phenotype acute leukemia
- •Trisomy 21
- •Current pregnancy
- •Previous or concurrent malignancy
- •Isolated myeloid sarcoma
- •Patients previously treated with antineoplastic therapy with the following exceptions:
- •Hydroxyurea
- •Corticosteroids
- •Intrathecal chemotherapy at diagnosis
研究组 & 干预措施
All patients with de novo AML
All patients with de novo AML presenting to Kamuzu Central Hospital in Lilongwe, Malawi will be offered enrollment into the study.
干预措施: Intensity-adapted pediatric acute myeloid treatment guidelines (Other)
结局指标
主要结局
Determine the implementation success of an intensity adapted clinical practice guideline (CPG) based upon recommendations by the International Society of Paediatric Oncology (SIOP) for childhood AML in resource limited settings.
时间窗: From initiation of chemotherapy to assessment of completion of the CPG and attainment of end-of-induction bone marrow evaluation (if CPG completed to that point), assessed up to 12 months from the start of chemotherapy.
CPG Implementation Success will be a composite endpoint comprised of: 1. Feasibility: proportion of patients completing the CPG. (see Study Design for further details outlining CPG completion criteria) 2. Effectiveness: proportion of patients in complete remission (CR) by the end of Induction 2 chemotherapy.
次要结局
- Estimate the proportion of patients with negative minimal residual disease (MRD) following Induction(By end of second induction, assessed up to 6 months from initiating chemotherapy.)
- Estimate the proportion of patients with early mortality(Assessed up to 42 days from start of chemotherapy)
- Estimate the proportion of patients with treatment-related mortality on the CPG(Assessed from Day 43 following initiation of chemotherapy through to completion of the CPG, assessed up to 12 months.)
- Estimate the proportion of patients with serious adverse events(From initiation of chemotherapy through to completion of the CPG, assessed up to 12 months.)
- Estimate the time to hematologic recovery following cycles of chemotherapy(From the final dose of curative-intent chemotherapy to blood product independence, assessed up to 6 months.)
- Estimate the proportion of patients with treatment abandonment.(From initiation of chemotherapy to completion of the CPG, assessed up to 12 months.)
- Estimate survival of patients treated with the CPG.(Assessed 24 months from start of therapy)
- Describe myeloblast cytogenetics(Time of diagnosis (samples are batched and assessed up to 6 months following diagnostic bone marrow evaluation))
- Describe Patient Reported Outcomes at relevant timepoints.(Assessed within 30 days of diagnostic bone marrow evaluation (diagnosis timepoints) and within 30 days of the end of second induction (mid-therapy time-point, assessed up to 6 months from diagnosis).)
- Determine the fidelity to treatment and supportive care practice guidelines associated with AML therapy in Malawi(From initiation of chemotherapy through to completion of the CPG, assessed up to 12 months.)
研究者
Mark Zobeck
Assistant Professor
Baylor College of Medicine