An observational study in Acute Myeloid Leukaemia, sponsored by Baylor College of Medicine. Recruiting at 1 site in Malawi. Open to participants aged Up to 18 Years. Per ClinicalTrials.gov, last updated 2026-07-15.
Sponsored by Baylor College of Medicine · Observational
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.
Participants:
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.
On-treatment schedule Patients are routinely admitted inpatient to the pediatric cancer unit at the start of each chemotherapy cycle. Patients remain inpatient according to standard practices of the unit until they no longer require routine blood product transfusions and their absolute neutrophil count is rising. Patients are discharged home for \~1 week prior to returning to start the subsequent cycle, but generally no later than 2 weeks from discharge.
Required Data Items are all routinely obtained as part of standard of care:
Required Data Items:
Statistical analysis:
Sample size determination of this study is based on accrual capacity of the study site, not from statistical power. Based on diagnoses over the previous three years at Kamuzu Central Hospital in Malawi, the investigators expect at least 10 de novo cases/year of AML.
Primary Endpoint
CPG Implementation Success will be a composite endpoint comprised of:
Implementation will be deemed successful if 1) ≥50% of patients are able to complete the CPG; AND 2) The historical benchmark of end-of-induction complete remission (CR) of 40% is maintained.
Rates of CR (effectiveness outcome) and CPG completion (implementation outcome) will be monitored continuously by the study statistician team using an adaptation of the method of Ivanova and colleagues. This method provides a Pocock-type boundary so that the probability of crossing the boundary is at most 5% when the true rate of the event crosses the acceptable threshold. For the effectiveness threshold of CR, we will use the established historical rate of CR of 40% achieved on the old standard of care for AML in Malawi. The probability of boundary crossing rises to 24%, 68%, and 98% if the CR rate drops to 30%, 20%, and 10%, respectively, with corresponding accruals of N=28, 22, and 14. Similarly, for rate of CPG completion, we will use a threshold of 50%. The probability of boundary crossing rises to 22%, 59%, and 92% if the rate of completion rate drops to 40%, 30%, and 20%, respectively, with corresponding expected accruals of N=27, 22, and 15.
Criteria for completing the CPG are:
Complete Remission is defined as \<5% myeloblasts on bone marrow evaluation.
Secondary Endpoints
3,667 studies on the registry are indexed under Leukemia, Myeloid, Acute; 816 are open to participants now.
This study's planned enrollment of 30 is below the median of 114 across 395 observational studies indexed under Leukemia, Myeloid, Acute.
Browse Leukemia, Myeloid, Acute studies →Baylor College of Medicine is the lead sponsor of 747 studies on the registry; 110 are open to participants now.
Of its 84 completed or terminated interventional studies of FDA-regulated products, 45 (54%) have results posted.
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All patients with de novo AML presenting to Kamuzu Central Hospital in Lilongwe, Malawi.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Diagnosis
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:
Exclusion Criteria:
Patients with any of the following conditions or criteria will be excluded from the study:
Patients previously treated with antineoplastic therapy with the following exceptions:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
All patients with de novo AML presenting to Kamuzu Central Hospital in Lilongwe, Malawi will be offered enrollment into the study.
Other: Intensity-adapted pediatric acute myeloid treatment guidelines
This is an observational study evaluating the current standard of care AML therapy in Malawi. The therapy guideline used is an adaptation of the International Society of Paediatric Oncology (SIOP) guidelines for pediatric AML in resource-constrained centers published by the International Society of Paediatric Oncology (SIOP). It is currently the standard of care in Malawi for all patients with AML. Receipt of this therapy guideline is independent of participation in research.
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.
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.
Time frame: 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.
Estimate the proportion of patients with negative minimal residual disease (MRD) following Induction
MRD will be evaluated by bone marrow examination with multiparameter flow cytometry. MRD positivity will be defined as ≥0.1% residual pathological myeloblasts.
Time frame: By end of second induction, assessed up to 6 months from initiating chemotherapy.
Estimate the proportion of patients with early mortality
Early mortality is defined as death occurring ≤42 days from the beginning of treatment.
Time frame: Assessed up to 42 days from start of chemotherapy
Estimate the proportion of patients with treatment-related mortality on the CPG
TRM will be defined as death occurring \>42 days from the beginning of treatment due to any cause in the absence of progressive cancer.
Time frame: 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
All adverse events among patients treated on the CPG will be graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5. All the Grade ≥3 adverse events will be recorded
Time frame: 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
Time to transfusion independence of blood products following completion of therapy.
Time frame: 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.
After starting Day 1 of therapy, any unplanned hiatus of curative-intent therapy lasting ≥4 weeks lasting ≥4 weeks.
Time frame: From initiation of chemotherapy to completion of the CPG, assessed up to 12 months.
Estimate survival of patients treated with the CPG.
Overall, event-free, and relapse-free survival 12 \& 24 months from diagnosis.
Time frame: Assessed 24 months from start of therapy
Describe myeloblast cytogenetics
Myeloblast cytogenetics is defined as reported by NanoString bone marrow analysis at diagnosis.
Time frame: Time of diagnosis (samples are batched and assessed up to 6 months following diagnostic bone marrow evaluation)
Describe Patient Reported Outcomes at relevant timepoints.
Patient-Reported Outcomes Measurement Information System (PROMIS-25) questionnaires will be given to parents and children enrolled on study at the time of diagnosis (within 30 days) and at the end of second Induction (within 30 days). Questionnaires will be administered by study personnel while patients are inpatient. As many families at the treatment center are illiterate, all questionnaires will be read and filled in by study personnel based on answers by the parents/children.
Time frame: 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
Proportion of discrete treatment and supportive care guideline elements received/completed as prescribed.
Time frame: From initiation of chemotherapy through to completion of the CPG, assessed up to 12 months.
Plan to share: No — Malawian data privacy laws prohibit open sharing of individual patient data. Aggregated data supporting study outcomes will be published as a scientific manuscript. Requests for IPD will be considered on a case-by-case basis by study investigators, following all applicable Malawian data privacy laws.
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