Health Trials

Leukemia Adapted Protocol

ConditionAcute Myeloid Leukaemia
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
AgeUp to 18
SponsorBaylor College of Medicine

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Diagnosis

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.

Disqualifiers

Juvenile myelomonocytic leukemia

Transient myeloproliferative disorder

Acute promyelocytic leukemia

Mixed phenotype acute leukemia

Trial population

All patients with de novo AML presenting to Kamuzu Central Hospital in Lilongwe, Malawi.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

  • Intensity-adapted pediatric acute myeloid treatment guidelines

    Other intervention

    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.

Treatment groups

30 Participants
are divided into 1 treatment group
Group A: All patients with de novo AML1 intervention

Trial outcomes

Primary outcomes

1

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.

Secondary outcomes

1

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.
2

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
3

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.
4

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.

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Baylor College of Medicine

Lead sponsor

American Society of Hematology

Collaborator

Source ClinicalTrials.gov
Apply now