Home-based Intravenous Cytarabine Treatment for Acute Myeloid Leukemia: a National Danish Study of Feasibility, Costs, and Implementation

Overview

The goal of this observational multicenter feasibility and implementation study is to evaluate home-based treatment with intravenous Cytarabine for patients with acute myeloid leukemia in Denmark. The study aims to generate research-based evidence on feasibility, safety, patient impact, health economic costs, and implementation of home-based intravenous chemotherapy treatment. The main questions it aims to answer are: 1\. What is the existing evidence on home-based chemotherapy treatment for patients with hematological malignancies, including feasibility, safety, symptoms, quality of life, and cost-effectiveness? 2\. Is home-based treatment with intravenous Cytarabine feasible and safe for patients with acute myeloid leukemia in Denmark? 3\. What are the costs, patient-reported outcomes, and caregiver roles related to home-based Cytarabine treatment? 4\. What are the key barriers and facilitators experienced by patients, caregivers, and healthcare professionals during home-based Cytarabine treatment? Which national strategies and recommendations can support the implementation, scalability, sustainability, and equitable access to home-based intravenous Cytarabine treatment across healthcare settings in Denmark?

Introduction Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by rapid proliferation of malignant blasts in the bone marrow, leading to suppression of normal hematopoiesis and bone marrow failure. Curative treatment typically involves intensive chemotherapy, often including intravenous Cytarabine (IV-Cytarabine), administered either as intermittent or continuous infusions. Due to the need for prolonged infusion and close clinical monitoring, patients are commonly treated during hospitalization or through repeated outpatient visits. This places a considerable burden on patients, caregivers, and healthcare systems, and may increase risks associated with prolonged hospital stays, including infections, reduced mobility, impaired nutrition, and decreased quality of life. New delivery models, including portable programmable infusion pumps, make it possible for selected patients to receive IV-Cytarabine at home. Home-based hematological care is increasingly recognized as a patient-centered model that may reduce hospital visits, support daily living, improve psychosocial well-being, and potentially lower risks related to hospitalization. Previous Danish studies have shown that home-based chemotherapy can be feasible, safe, and acceptable to patients. However, current evidence remains limited, and no national or international guidelines exist to support systematic implementation of home-based hematological treatment. Important gaps remain regarding organizational models, safety, feasibility, health economic costs, patient-reported outcomes, caregiver involvement, and long-term sustainability. Preliminary findings from the Treat@Home program indicate that home-based treatment is already used in Denmark, but access is unequal, data registration is inconsistent, and the evidence base is limited. The HOME-CALM study therefore aims to generate robust evidence on home-based IV-Cytarabine for patients with AML in Denmark. This knowledge will support the development of national recommendations and sustainable, equitable care pathways for home-based intravenous chemotherapy. Hypothesis This study is based on the following assumptions and hypotheses. Study 2 Home-based IV-Cytarabine treatment for patients with AML is feasible and safe when compared to inpatient or outpatient treatment settings, reducing the burden on healthcare systems and supporting everyday lives. Study 3 Key barriers to home-based IV-Cytarabine treatment include lack of patient and caregiver education, low level of health literacy, and challenges in coordination with HCPs across sectors, while facilitators include effective communication, support systems, and tailored treatment plans. Study 4 Key facilitators to implementing home-based IV-Cytarabine treatment are related to effective intersectoral coordination, clearly defined roles for HCPs, adequate guidelines for practice, and patient and caregiver education. Aims The overall aim is to develop research-based evidence on feasibility, impact, and implementation of home-based interventions for AML patients receiving IV-Cytarabine in Denmark, which will result in a national guideline for home-based intravenous chemotherapy treatment. These goals will be accomplished by investigating practice, safety, organizational frameworks, health economic costs, and associated barriers and facilitators in delivering and managing home-based IV-Cytarabine treatment in this population. Specific study aims are: Study 1 To summarize the existing research-based evidence on home-based interventions with chemotherapy treatment. Specifically, it aims to identify, collate, and assess studies that investigate the feasibility and safety of home-based interventions with chemotherapy, their influence on symptoms and quality of life, and their impact on cost-effectiveness in patients with hematological malignancies. Study 2 To evaluate the feasibility of implementing home-based treatment with Cytarabine to patients with acute leukemia in Denmark. Further to examine the costs associated with a home-based treatment with Cytarabine in a clinical setting, and to examine QoL, symptoms and health literacy in patients as well as roles and responsibilities in their caregivers, while receiving treatment at home Study 3 To explore the experiences and perspectives on barriers and facilitators during home-based treatment with Cytarabine among patients, caregivers, and HCPs across health sectors. Study 4 To develop and deploy strategies at a national level to support and enhance the adoption and long-term sustainability of home-based treatment with Cytarabine to patients with acute leukemia. Specifically, to develop evidence-based recommendations to optimize delivery, ensure scalability, and promote equitable access across diverse healthcare settings. Methods A multimethod design will be applied in that both quantitative and qualitative methods will be used to strengthen the types of data material and to adequately answer the research aims. This research protocol is inspired by the methodological framework for developing and evaluating complex interventions described by the Medical Research Council (MRC). Complex intervention research consists of multiple phases (identification, feasibility, evaluation, and implementation) ensuring that core elements essential to the research process are addressed. Home-based treatment is classified as a complex intervention, and by using an already implemented intervention aligns with the MRC iterative nature, focusing on evaluating, optimizing, and scaling complex interventions in real-world contexts. This approach not only leverages existing evidence but also ensures practical, ethical, and resource-efficient research that can directly inform policy and practice. Consequently, this protocol consists of four studies representing the MRC framework´s four phases. In accordance with the MRC framework, knowledge gained from study 1 will inform study 2 and 3, and findings from study 2 and study 3 will inform study 4. Identification: Study 1 will identifying the current international evidence and practice of home-based treatment. Feasibility: Study 2 will assess the feasibility, safety, organization, and health economic costs home-based treatments with IV-Cytarabine. Evaluation: Study 3 will evaluate home-based treatment using a qualitative design to gain a comprehensive understanding of the intervention´s impact, facilitating more effective implementation and refinement. Implementation: Finally, using an implementation framework study 4 will evaluates implementation of home-based treatment focusing on its adaptation, optimization, sustainability, and scalability. Overview of evidence. An initial step will be to provide a comprehensive overview of the current research-based evidence on home-based chemotherapy interventions for patients with hematological malignancies. Specifically, the investigators will identify, collate, and critically assess existing studies that examine the feasibility, safety, and impact of such interventions on patient-reported outcomes, including symptoms, quality of life, and cost-effectiveness. These findings will serve as a foundational evidence base to guide the subsequent studies. Specifically, it will inform the design and focus of the feasibility evaluation in Study 2 by highlighting best practices, gaps in current knowledge, and key implementation challenges reported in prior research. Moreover, insights into the contextual factors and outcomes of home-based chemotherapy from diverse healthcare settings will contribute to a deeper understanding of potential facilitators and barriers, which will be further explored through qualitative methods in Study 3. Feasibility approach. The study will adopt the Consolidated Framework for Implementation Research (CFIR) as our overall framework for the evaluation. CFIR consists of five major domains: Intervention Characteristics, Outer Setting, Inner Setting, Characteristics of Individuals, and Process. It includes a total of 39 constructs that facilitate a comprehensive analysis of both barriers and facilitators to implementation. In cancer research, the primary objective is to implement evidence-based interventions that demonstrate effectiveness. Efficacy studies assess intervention outcomes under ideal conditions, whereas effectiveness studies evaluate how well interventions perform in real-world, less controlled settings. The UK's National Institute for Health Research differentiates between feasibility studies and pilot studies. Feasibility studies explore whether a study is possible to carry out, while pilot studies serve as small-scale versions of the main study. Feasibility studies, therefore, aim to assess the development and implementation process of an intervention and help determine whether it is appropriate to proceed with efficacy testing. The feasibility approach is crucial because, although home-based treatment is widely implemented, it lacks strategic implementation strategies, leading to unequal access, limited evidence, and inconsistent data recording across the country. At the same time, there is no existing evidence on effective implementation practices in this area. Qualitative approach. Qualitative methods will be employed to explore human experiences and actions within their social contexts, thereby facilitating a deeper understanding of the phenomena under investigation. The aim of study 3 is to gain insight into the experiences and perspectives of patients, caregivers, and HCPs across health sectors involved in home-based treatment with the goal of generating new knowledge about the nature and impact of barriers and facilitators during home-based treatment with Cytarabine. Study description - Study 1: Aim. To summarize the existing research-based evidence on home-based interventions with chemotherapy treatment, and its influence on symptoms and quality of life in patients with hematological malignancies. Design and methods. This systematic review will follow the PRISMA guidelines: "Preferred Reporting Items for Systematic Reviews and Meta-Analysis" (Page et al. 2021). The study will be registered at the international register of systematic reviews PROSPERO. Search strategy Four databases will be searched from 2004 to 2024: Public Medline (MEDLINE/PUBMED), EMBASE, Cumulative Index of Nursing and Allied Health (CINAHL) and APA PsycINFO (PSYCINFO). The search strategy will be developed using a matrix based on the principles from PICO (Population, intervention, control, and outcome), and will comply into three search focuses (population, intervention and outcomes). The matrix will consistently be applied to all selected databases and include 1) Hematological malignancies (population), 2) Home-based chemotherapy treatment (Intervention), and 3) Cost-effectiveness analysis and/or symptoms and/or quality of life (Outcomes). A combination of MeSH terms, thesaurus, indexed terms, and free text for the three search focuses will be used. An academic librarian before initiation will validate the search strategy. In addition, PROSPERO will be searched for ongoing systematic reviews related to the scope of this systematic review. Eligibility criteria and outcomes Studies are eligible for inclusion in this systematic review if they meet the following criteria: 1) Enrolled patients \> 18 years with a hematological malignancy regardless of stage or type of treatment 2) Investigate home-based interventions with chemotherapy treatment, 3) Included the following outcomes: disease and treatment-related symptoms and/or QOL measured on validated questionnaires and/or Cost-effectiveness analysis. Study selection and quality assessment. Covidence will be used to manage and screen all studies considered relevant and are then read in full. The studies are then categorized as either included, unclear (for further discussion), or excluded based on the inclusion criteria. Any discrepancies relating to whether a paper should be included in the review will be discussed by the reviewers. If no agreement could be achieved, then this will be discussed at team meetings by the entire team until consensus are reached. In case of overlapping data sets presented in different studies, the most resent publications will be included. Critical Appraisal Checklists (CASP) will be used to evaluate the methodological quality and assessed risk of bias in the included studies. The following information will systematically be extracted from all the included articles: study authors, date of publication, study population and participant characteristics (sample size, age, gender, country of origin, type of hematologic malignancy, study methodology, setting and duration), method of outcome measurement, study outcomes and results. Where possible, data on experimental conditions, including the number of study arms, name and description of intervention(s) and comparator(s) groups will also be extracted. Data extraction. The study will not do a meta-analysis because of expected heterogeneity in design and outcomes across the small number of existing trials. Instead, the researchers involved will synthesize outcomes using a narrative approach including tables and figures to aid in data presentation where appropriate. These data will be extracted independently by 2-4 researchers, and after discussion rounds, all researchers will agree upon the finalized version of the synthesized data. The following outcomes will be synthesized; feasibility (satisfaction, challenges) and safety (hospital admissions, adverse events), outcomes (symptoms and quality of life), and cost-effectiveness measures (number of saved visits to hospital/inpatient days), infusion (type of CVC, continuous vs bolus), who administer the treatment (patient, caregiver, health professional), where are the treatment administered (hospital, home). Synthesis The Synthesis Without Meta-analysis (SWiM) guideline will be used to promote transparent reporting. To obtain clinical applicability, studies will be grouped primarily based on the basis of type of treatment administered at home. Study description - study 2: Aim. To evaluate the feasibility of implementing home-based treatment with IV-Cytarabine to patients with AML in Denmark. Further to examine the costs associated with a home-based treatment with IV-Cytarabine in clinical settings, and to examine QoL, symptoms and health literacy in patients as well as roles and responsibilities for their caregivers, while receiving treatment at home. Design and methods. This is a single-arm prospective observational feasibility study for patients diagnosed with acute myeloid leukemia receiving treatment with IV-Cytarabine either as stand-alone treatment or in combination, in a real-world, standard practice setting. The study will be conducted in accordance with The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: guidelines for reporting observational studies. Study population. Participants that have been diagnosed with AML, aged ≥ 18 years, who are to receive treatment with IV-Cytarabine and their appointed primary caregiver, who can provide informed consent are eligible for inclusion. A primary caregiver is defined as an individual providing frequent support and attending to the physical and emotional needs of someone requiring ongoing assistance. Inability to read, write and/or speak Danish or English, or otherwise deemed unethical to participate due to mental disability, are ineligible for inclusion in the study. Recruitment procedure. Patients and their primary caregiver, identified by patients, will be recruited from all Danish hematologic departments offering home-based IV-Cytarabine treatment: Copenhagen University Hospital, Odense University Hospital, and Zealand University Hospital. Data collection timepoints are defined in accordance with the treatment regimen, ensuring consistency across sites and comparability of outcomes. The study will observe both induction- and consolidation phase. If the patients are hospitalized during initial or following treatments, data will still be collected, however, time-utilization will not be assessed. Specifically, assessments are scheduled at Cycle 1 * Treatment Initiation (C1TI, t0), * Treatment Completion (C1TC, t1) * Hematological Recovery (C1HR, t2) Cycle 2 * Treatment Initiation (C2TI, t3) * Treatment Completion (C2TC, t4) * Hematological Recovery (C2HR, t5) Cycle 3 * Treatment Initiation (C3TI, t6) * Treatment Completion (C3TC, t7) * Hematological Recovery (C3HR, t8) Cycle 4 * Treatment Initiation (C4TI, t9) * Treatment Completion (C4TC, t10) * Hematological Recovery (C4HR, These timepoints are anchored to key clinical events within the treatment cycles, thereby reflecting relevant changes in patient status and treatment progression. Primary outcomes. The primary outcomes are feasibility outcomes related to home-based treatment with IV-Cytarabine in a real-world clinical setting. Feasibility will be evaluated through recruitment, adherence, retention, acceptability, practicability, safety, and cost-effectiveness. Acceptability will be assessed using the Theoretical Framework of Acceptability questionnaire, which evaluates affective attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness, and self-efficacy. Secondary outcomes. Quality of life will be assessed using the EORTC QLQ-C30. Health literacy will be assessed using the Danish version of the Health Literacy Questionnaire. Caregiver roles and responsibilities will be assessed using the Caregiver Roles and Responsibilities Scale. Patient and caregiver experiences of time and energy expenditure related to home-based treatment will be assessed using a self-developed questionnaire. Symptoms and patient-reported safety outcomes will be assessed using the EORTC QLQ-C30 and supplemented by clinical data from electronic health records. Health economic outcomes will include healthcare and non-healthcare resource use. This includes healthcare professional time, use of CADD pumps and materials, training of staff, patients and caregivers, number of hospital contacts, inpatient and outpatient visits, virtual contacts, and treatment administrations at home or in hospital. Baseline data. Baseline data will include patient demographics, clinical characteristics, AML type, previous treatment, prescribed treatment regimen, and relevant blood test results. Caregiver baseline data will include demographic information and information on family and employment status. Patient-reported outcomes will be collected electronically via e-Boks at baseline, C2TC, C4TC, and at the end of IV-Cytarabine treatment. The TFA questionnaire will be collected at C2TC, C4TC, and at end of treatment. If participants are unable to complete the questionnaires electronically, project staff will assist by telephone. Safety and support. Safety data will be collected continuously throughout study participation. Adverse events and serious adverse events will be classified according to CTCAE version 5.0. Particular attention will be given to infections, complications requiring hospital-based intervention, treatment delays, interruptions, and issues related to home administration. Data on deviations from the planned treatment pathway, including clinical complications, technological issues, logistical challenges, or return to hospital care, will be collected from electronic health records and telephone interviews. Analysis. Feasibility outcomes, safety data, patient-reported outcomes, and health economic data will primarily be analyzed using descriptive statistics. Categorical variables will be summarized as numbers and percentages, and continuous variables as means with standard deviations or medians with ranges, depending on data distribution. Sample size. Based on methodological guidance for pilot and feasibility studies, the above-described rules of thumb, and considering practical constraints, the study aim to recruit 15 participants per site, in total 75 participants. This sample is expected to provide sufficient information to estimate key feasibility parameters with reasonable precision and allows us to explore variability in implementation processes across the included departments. While a relatively balanced contribution across regions is preferred to support exploration of variability in implementation processes, recruitment targets should be considered pragmatic rather than fixed quotas, acknowledging potential differences in patient volume and eligibility across sites. Ethical considerations. The study will be conducted in accordance with the Declaration of Helsinki and the General Data Protection Regulation (GDPR) as implemented under Danish law. The project has been assessed by the Regional Committees on Health Research Ethics (VEK) and found not to be notifiable to the Danish research ethics committee system, cf. Section 14(1) of the Danish Act on Research Ethics Review of Health Research Projects \[case number S-20262000 - 121\]. Participation is voluntary, and written informed consent will be obtained from all participants prior to inclusion. The study population is considered vulnerable, and efforts will be made to minimize participant burden and ensure that study activities do not interfere with treatment or add unnecessary stress to patients or caregivers. Participants may withdraw at any time without consequences for their current or future treatment. Data will be handled confidentially and stored securely in accordance with Danish data protection requirements. Personal identifiers will be removed from datasets, access will be restricted to authorized research personnel, and results will be reported in aggregate form to ensure participant anonymity.