Overview

Eligibility

Design Details

Arms & Interventions

Outcome Measures

Trial Sites

Source: NCT06928909

Recruiting

LEAP: Leukemia Adapted Protocol

Observational

Phase not listed

Kamuzu Central Hospital

Sponsor: Baylor College of Medicine

Last Updated: April 15, 2025
Notice- Information is sourced from public registries and may not reflect real-time changes at the local site.

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.

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Treatment Category

Other

Required Mutations

None

Trial Started

January 1, 2025

Last Updated by Sponsor

April 15, 2025

Estimated Completion

December 31, 2028

Contact Study

Name:Casey McAtee, M.D., M.P.H.

Email:casey.mcatee@bcm.edu

Phone:+1 251-605-5370

Eligibility

Inclusion Criteria

1. Age Patients must be <18 years of age at time of study enrollment.

2. 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:

* 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.

3. Therapy Patients must begin treatment according to the 2023 KCH AML therapy CPG.

Exclusion Criteria

1. 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

2. Patients previously treated with antineoplastic therapy with the following exceptions:

* Hydroxyurea

* Corticosteroids

* Intrathecal chemotherapy at diagnosis

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Design Details

AllocationN/A

Intervention ModelN/A

MaskingN/A

Number to Enroll30

Arms & Interventions

Arms

Interventions

Type: N/A

Description: All patients with de novo AML presenting to Kamuzu Central Hospital in Lilongwe, Malawi will be offered enrollment into the study.

Interventions:

Intensity-adapted pediatric acute myeloid treatment guidelines

Outcome Measures

Primary Outcome Measures

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.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.

Secondary Outcome Measures

Estimate the proportion of patients with negative minimal residual disease (MRD) following InductionBy end of second induction, assessed up to 6 months from initiating chemotherapy.

MRD will be evaluated by bone marrow examination with multiparameter flow cytometry. MRD positivity will be defined as ≥0.1% residual pathological myeloblasts.

Estimate the proportion of patients with early mortalityAssessed up to 42 days from start of chemotherapy

Early mortality is defined as death occurring ≤42 days from the beginning of treatment.

Estimate the proportion of patients with treatment-related mortality on the CPGAssessed from Day 43 following initiation of chemotherapy through to completion of the CPG, assessed up to 12 months.

TRM will be defined as death occurring >42 days from the beginning of treatment due to any cause in the absence of progressive cancer.

Estimate the proportion of patients with serious adverse eventsFrom initiation of chemotherapy through to completion of the CPG, assessed up to 12 months.

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

Estimate the time to hematologic recovery following cycles of chemotherapyFrom the final dose of curative-intent chemotherapy to blood product independence, assessed up to 6 months.

Time to transfusion independence of blood products following completion of therapy.

Estimate the proportion of patients with treatment abandonment.From initiation of chemotherapy to completion of the CPG, assessed up to 12 months.

After starting Day 1 of therapy, any unplanned hiatus of curative-intent therapy lasting ≥4 weeks lasting ≥4 weeks.

Estimate survival of patients treated with the CPG.Assessed 24 months from start of therapy

Overall, event-free, and relapse-free survival 12 & 24 months from diagnosis.

Describe myeloblast cytogeneticsTime of diagnosis (samples are batched and assessed up to 6 months following diagnostic bone marrow evaluation)

Myeloblast cytogenetics is defined as reported by NanoString bone marrow analysis at diagnosis.

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).

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.

Determine the fidelity to treatment and supportive care practice guidelines associated with AML therapy in MalawiFrom initiation of chemotherapy through to completion of the CPG, assessed up to 12 months.

Proportion of discrete treatment and supportive care guideline elements received/completed as prescribed.

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Trial Sites

This study has 1 trial site

Kamuzu Central Hospital

Lilongwe, MW

Name:Casey McAtee, M.D., M.P.H.

Recruiting

Lilongwe, MW

Kamuzu Central Hospital

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