Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neutropenia

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Granulocytopenia

Acute Graft Versus Host Disease

One qualitative, semi-structured interview will be conducted. Each interview will last approximately 30-45 minutes and may be audio recorded (if consent is provided). Interviews will consist of several open-ended questions focusing on having the participant reflect upon past experiences with neutropenia management and the impact of the participant's illness and treatment. Several close-ended questions regarding participant's thoughts on potential outcomes will also be included.

One qualitative, semi-structured interview will be conducted. Each interview will last approximately 30-45 minutes and may be audio recorded (if consent is provided). Interviews will consist of several open-ended questions focusing on having the participant reflect upon past experiences with neutropenia management and the impact of their child's illness and treatment. Several close-ended questions regarding participant's thoughts on their child's potential outcomes will also be included.

Richard Aplenc, MD, PhD

The primary objectives of this study are to identify what outcomes related to the management of neutropenia are most important to children with AML and their caregivers. Patients who have completed treatment for AML and their caregivers will be interviewed in order to better understand the impact of neutropenia management on children with AML and their families. The primary outcome of these interviews is to identify patient-centered outcomes related to neutropenia management to include in a subsequent comparative-effectiveness analysis. Investigators will use these data to develop a structured survey for administration to prospectively identified patients in subsequent studies.

Treatment for pediatric acute myeloid leukemia (AML) involves intensive chemotherapy regimens that result in periods of profound neutropenia leaving patients susceptible to severe infectious complications. There are little clinical data to inform whether management of neutropenia post AML chemotherapy should occur in an outpatient or inpatient setting. Further, no studies have been conducted that assess the impact of neutropenia management strategy on the quality of life of pediatric patients with AML. Given that infectious complications are the leading cause of treatment related mortality among AML patients, it is important to identify the neutropenia management strategy that will lead to the best clinician- and patient- identified outcomes in order to improve the care of these patients.

This is a qualitative interview study where interviews of patients and/or caregivers will be performed. Participants will be patients less than 19 years of age at diagnosis (and their caregivers) receiving or having received chemotherapy for AML from eleven participating pediatric hospitals across the United States. Participants (children and caregivers) will be interviewed in an effort to develop a survey that captures patient- and caregiver- identified outcomes related to neutropenia management.

Home or Away From Home - Descriptive Interviews (Aim 2)

Home or Away From Home: Patient-Centered Outcomes Related to the Management of Neutropenia Which Are Most Important to Children With AML and Their Caregivers

Only aggregate level data will be shared with the study sponsor Patient-Centered Outcomes Research Institute (PCORI).

Issues related to type of neutropenia management are not quantifiable. All interviewees gave unique responses to issues related to neutropenia management, and themes were identified after all interviews were conducted and analyzed.

Patient-Centered Outcomes Research Institute

Primary Children's Hospital

Texas Children's Cancer Center

Children's Healthcare of Atlanta

C.S. Mott Children's Hospital

Children's Medical Center Dallas

Arkansas Children's Hospital Research Institute

Ann & Robert H Lurie Children's Hospital of Chicago

Children's Hospital of Michigan

Lucile Packard Children's Hospital

Seattle Children's Hospital

Children's Hospital of Philadelphia

There is no study intervention; this is a qualitative interview study only, thus adverse events were a non-issue and not monitored or assessed.

Participants

Caregivers

Patients who participated in a qualitative interview about their experience with AML. One qualitative, semi-structured interview was conducted. Each interview lasted approximately 30-45 minutes and may be audio recorded (if consent is provided).

Patients

Caregivers who participated in a qualitative interview about their experience with AML. One qualitative, semi-structured interview was conducted. Each interview lasted approximately 30-45 minutes and may be audio recorded (if consent is provided).

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Dr. Richard Aplenc

One qualitative, semi-structured interview will be conducted. Each interview lasted approximately 30-45 minutes and were audio recorded (if consent is provided). Interviews consisted of several open-ended questions focusing on having the participant reflect upon past experiences with neutropenia management and the impact of the participant's illness and treatment. Several close-ended questions regarding participant's thoughts on potential outcomes were also included.

All participants (patients and caregivers) who participated in the semi-structured interviews. 3 key, novel themes were identified across these interviews.

Issues Related to Type of Neutropenia Management That Are Most Important to Children and Their Caregivers.

Overall Study

Behaviors and Mental Disorders

Neoplasms by Histologic Type

Hematologic Diseases

Quality of Life

Patients receiving or having received chemotherapy for AML who are discharged to outpatient management within 3 days after chemotherapy completion. Subjects will complete a health related quality of life (HRQOL) survey at baseline and again at the start of the next treatment course. Survey questions will collect information such as patient race and educational level.

Patients receiving or having received chemotherapy for AML who remain in the hospital more than 3 days after chemotherapy completion. Subjects will complete a health related quality of life (HRQOL) survey at baseline and again at the start of the next treatment course. Survey questions will collect information such as patient race and educational level.

Treatment for pediatric acute myeloid leukemia (AML) involves intensive chemotherapy regimens that result in periods of profound neutropenia leaving patients susceptible to severe infectious complications. Infectious complications are the leading cause of treatment related mortality among AML patients, but there are little clinical data to inform whether management of neutropenia post AML chemotherapy should occur in an outpatient or inpatient setting. Further, no studies have been conducted that assess the impact of neutropenia management strategy on the quality of life of pediatric patients with AML and their caregivers.

This is a prospective observational cohort study, where the primary objective of this study is to compare patient and caregiver quality of life and other patient-centered outcomes for inpatient versus outpatient management of neutropenia in children with AML or MDS receiving standard intensive AML frontline chemotherapy.

Local study investigators (pediatric oncologists and study coordinators) at each of the fifteen participating pediatric institutions will communicate on a weekly basis with their inpatient leukemia service to identify AML or MDS patients potentially eligible for study enrollment. Once identified, study personnel will review each patient for study eligibility criteria. Three visits with the patient and their caregivers will occur: a screening visit, initial survey visit, and a follow-up visit.

Screening Visit: The eligibility criteria for participation will be confirmed prior to approaching for consent. Eligible patients interested in the study will be approached for consent at any time from AML/MDS diagnosis through last day of chemotherapy in the treatment course under study. In some cases, the patient's caregivers may not be present in the hospital to provide consent. In these cases, study personnel will obtain verbal consent from the caregivers and child assent (if appropriate).

Visit 1 will occur prior to the last day of chemotherapy administration in the course. This visit will include:

* 2 Brief demographic surveys to capture covariates unavailable in the medical record
* Baseline health-related quality of life (HRQOL) surveys
* A baseline financial toxicity assessment

Surveys will be administered via paper or a smart device and will last a total of 15-30 minutes per respondent. In the case that the child is 5 years of age or older, the child self-report and parent proxy-report scales will be separately administered to the child and caregiver, respectively. If the child is under 5 years of age, only the parent-proxy version will be administered. Only the caregiver completes the baseline financial toxicity assessment. We will provide a $25 gift card to each child-parent dyad upon completion of the baseline surveys

Visit 2 will occur within the period after absolute neutrophil count recovery and ideally prior to the start of the subsequent course of chemotherapy, but no later than the last day of chemotherapy in that next treatment course. This visit will include:

* Follow-up HRQOL surveys
* Patient-centered outcome survey developed previously from qualitative interviews of AML patients and their caregivers
* A follow-up financial toxicity assessment

Surveys will be administered via paper or a smart device and will last a total of 15-30 minutes per respondent. In the case that the child is 5 years of age or older, the child self-report and parent proxy-report scales will be administered to the child and caregiver, respectively. If the child is under 5 years of age, only the parent-proxy version will be administered. The follow-up financial toxicity assessment and the patient-centered outcome survey are completed by the caregiver only. We will provide a $25 gift card to each child-parent dyad upon completion of the follow-up surveys.

Home Away From Home - Quality of Life Surveys

Home or Away From Home: Comparing Patient and Caregiver Reported Quality of Life (QoL) and Other Patient-centered Outcomes for Inpatient Versus Outpatient Management of Neutropenia in Children With AML

only aggregate and de-identified data will be shared upon appropriate request.

1 Course of Chemotherapy (Approximately 30-40 days). The primary outcome of interest was patient health-related quality of life (HRQOL) measured using the acute PedsQL™ 4.0 Generic Core Scales.31 These scales use a 7-day time frame. The multidimensional assessment includes items in four domains: physical functioning, emotional functioning, social functioning, and school functioning. Respondents document responses to each question using a 5-point Likert scale anchored by never a problem (0) to almost always a problem (4). PedsQL™ items were reverse scored and linearly transformed to a scale of 0 to 100 such that higher scores reflect better HRQOL.

Information from semi-structured patient outcome surveys completed by patients and caregivers will be collected to evaluate the relationship between neutropenia management strategy (inpatient versus outpatient) and outcomes reported by patients and caregivers.

Baylor College of Medicine

St. Jude Children's Research Hospital

Alfred I. duPont Hospital for Children

Children's Hospital Colorado

Dana-Farber Cancer Institute

There was no study intervention, only survey administration and collection.

Patients receiving or having received chemotherapy for AML who are discharged to outpatient management within 3 days after chemotherapy completion. Subjects will complete a health related quality of life (HRQOL) survey at baseline and again at the start of the next treatment course. Survey questions will collect information such as patient race and educational level.

HRQOL questions will be scored on a 5-point Likert response scale (0=never a problem to 4=almost always a problem). The total score includes a 23 item multidimensional core (physical, emotional, social and school functioning); an 18 item multidimensional fatigue scale (general, sleep/rest and cognitive fatigue) and a 27 item multidimensional cancer module (pain, nausea, anxiety, communication, and cognitive problems). Total score is calculated with a lower score representing a higher health related quality of life.

Early Discharge Patients

Patients receiving or having received chemotherapy for AML who remain in the hospital more than 3 days after chemotherapy completion. Subjects will complete a health related quality of life (HRQOL) survey at baseline and again at the start of the next treatment course. Survey questions will collect information such as patient race and educational level.

HRQOL questions will be scored on a 5-point Likert response scale (0=never a problem to 4=almost always a problem). The total score includes a 23 item multidimensional core (physical, emotional, social and school functioning); an 18 item multidimensional fatigue scale (general, sleep/rest and cognitive fatigue) and a 27 item multidimensional cancer module (pain, nausea, anxiety, communication, and cognitive problems). Total score is calculated with a lower score representing a higher health related quality of life.

Inpatient Management Patients

Race

Race/Ethnicity, Customized

Hispanic Ethnicity

Of the 154 consented patients, only 97 were discharge eligible or within the analyzed population, thus only 97 patients were analyzed.

Participants who completed evaluable PedsQL follow-up surveys.

Compare Differences in HRQOL Scores Between Outpatient Versus Inpatient Management

Responses From Structured Patient-centered Outcome Surveys

Symptoms and General Pathology

Diseases and Abnormalities at or Before Birth

Immune System Diseases

Nutritional and Metabolic Diseases

Syndrome

Preleukemia

Myelodysplastic Syndromes

Anemia, Sickle Cell

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Anemia

Thalassemia

Anemia, Aplastic

Vitamin D Deficiency

Lymphoma

Bone Marrow Diseases

Hemolysis

Anemia, Hemolytic

Anemia, Hemolytic, Congenital

Hemoglobinopathies

Genetic Diseases, Inborn

Avitaminosis

Deficiency Diseases

Malnutrition

Nutrition Disorders

Bone Marrow Failure Disorders

Pancytopenia

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Sickle Cell Anemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Aplastic Anemia

Childhood Acute Lymphoblastic Leukemia

Lymphosarcoma

Micronutrients

All Drugs and Chemicals

Bone Density Conservation Agents

Vitamins

Vitamin D

Cholecalciferol

Hydroxycholecalciferols

Calcifediol

Ergocalciferols

Trace Elements

Hormones

Calcium

Calcium, Dietary

Vitamin D3

Calciferol

Ergocalciferol

Vitamin D2

Patients will take a single oral dose of vitamin D3 based on age and initial vitamin D level. A patient will be classified as sufficient, insufficient, or deficient at the start of therapy. Following this dose, patients will also be given standard vitamin D3 supplementation according to current Endocrine Society Guidelines.

Patients will be given standard vitamin D3 supplementation during transplant in accordance with standard of care per Endocrine Society Guidelines. This supplementation is based on a patient's initial vitamin D level.

The single, oral dose of vitamin D3 is based on patient's age and baseline 25-hydroxy-vitamin D level. Dosing is as follows: (1) For children under 3 years of age. 200000IU for those deficient, 150000IU for those insufficient, and 100000IU for those sufficient; (2) For children 3-12 years of age, 400000IU for those deficient, 350000IU for those insufficient, and 200000IU for those sufficient; (3) For children greater than 12 years of age, 600000IU for those deficient, 500000IU for those insufficient, and 300000IU for those sufficient. This is a single, one time oral dose given prior to the start of transplant.

Those who have sufficient vitamin D will be supplemented with 400-600IU/day of Vitamin D3 orally.

Those who have insufficient or are deficient in vitamin D will be supplemented with 50,000IU/week of Vitamin D3 orally.

Standard Vitamin D3 Supplementation

Alexander Ngwube, MD

Kayla Burgett

Research has suggested that children with sufficient vitamin D levels undergoing hematopoietic stem cell transplant (HSCT) have improved outcomes, including lower incidences of infection and graft-versus-host disease (GVHD), as well as overall improved survival. However, supplementation in children undergoing HSCT has shown to be a challenge using standard or aggressive supplementation strategies. The primary objective of this study is to determine the safety and efficacy of a single, high dose oral vitamin D (Stoss Therapy) at the start of transplant followed by maintenance supplementation in children undergoing HSCT.

Comorbidities and complications including infection, organ system toxicity, graft-versus-host disease (GVHD) and disease recurrence are some of the biggest contributors to quality of life and mortality in children undergoing hematopoietic stem cell transplant (HSCT). Research has suggested that patients with sufficient vitamin D levels during transplant have improved outcomes, including lower incidences of infection and acute GVHD, as well as overall improved survival. Prior research has shown that chronically ill children are at risk for vitamin D deficiency, including those undergoing HSCT. Data has shown populations with as many as 70% of HSCT patients have insufficient levels of vitamin D at time of transplant. While several studies have attempted methods of vitamin D supplementation in this subset of patients, there has not been success with either standard or aggressive supplementation strategies.

Single high-dose oral vitamin D therapy, known as stoss therapy, has been used in other chronically ill children where adequate levels of vitamin D are difficult to attain. Stoss therapy suggests a single high-dose followed by maintenance dosing would be adequate to replete and maintain vitamin D levels in chronically ill children. While it has been shown to be effective with no evidence of toxicity in patients with rickets and cystic fibrosis, its safety and efficacy has not been studied in the transplant setting. However, there is an urgent need to identify a modifiable factor may reduce the occurrence and/or severity of HSCT associated complications. The overall objective of this study is to determine the effectiveness of a single, high dose oral vitamin D (Stoss Therapy) followed by maintenance supplementation in children undergoing HSCT. This change will result in a new and innovative approach to maintaining adequate vitamin D levels during pediatric HSCT, with the long term goal of reducing morbidity and mortality.

Our primary goal is to assess the safety and efficacy of a single, high dose of vitamin D followed by maintenance supplementation in children undergoing HSCT. Our secondary goal is to identify the effects of adequate vitamin D levels on early clinical outcomes such as cytokine levels, graft versus host disease, immune recovery, rejection, relapse, infection rates in pediatric HSCT patients.

Patients enrolled in the study will be randomized to either a control or intervention arm prior to the start of transplant using block randomization of blocks of 6. Those randomized to the intervention arm will receive the intervention (Stoss Therapy dosing of vitamin D) at the start of transplant followed by maintenance supplementation of vitamin D according to standard of care. Those randomized into the control arm will receive only maintenance supplementation of vitamin D according to standard of care throughout transplant.

A Randomized Phase IV Control Trial of Single High Dose Oral Vitamin D3 in Pediatric Patients Undergoing HSCT

A Randomized Phase IV Control Trial of Single High Dose Oral Vitamin D3 (Stoss Therapy) in Pediatric Patients Undergoing HSCT to Prevent Vitamin D Deficiency and Insufficiency During Transplant

In order to monitor the safety of stoss therapy, patients will be monitored for any clinical signs or symptoms of hypervitaminosis D, including abdominal pain, dehydration, and fatigue. Patients will be monitored for hypercalcemia and hyperphosphatemia with weekly complete metabolic panels and serum phosphorus during the first 100 days of transplant. Patients will have repeat measurements of serum 25(OH)D levels will be obtained at Day +30 to ensure they do not have hypervitaminosis D at that time.

All patients will have baseline serum 25(OH)D levels obtained prior to transplant. At baseline, patient will be classified as being sufficient (\>30ng/mL), insufficient (21- 29ng/mL), or deficient (\<20ng/mL) in serum vitamin D. All patients will then undergo treatment based on their trial arm and baseline levels of vitamin D. Patients will have repeat measurements of serum 25(OH)D levels will be obtained at Day +100 of transplant. At this time they will again be classified as being sufficient (\>30ng/mL), insufficient (21- 29ng/mL), or deficient (\<20ng/mL) in serum vitamin D following therapy to assess if the therapy was efficacious in repleting and maintaining their serum vitamin D level.

All incidences of GVHD will be recorded in the medical record throughout transplant as per standard of care for data extraction after Day +100

Immune recovery will be obtained at Day +100 as per standard of care and recorded in the medical record

All incidences of rejection will be recorded in the medical record throughout transplant as per standard of care for data extraction after Day +100

All incidences of relapse will be recorded in the medical record throughout transplant as per standard of care for data extraction after Day +100

All incidences of infection will be recorded in the medical record throughout transplant as per standard of care for data extraction after Day +100

All incidences of mortality will be recorded in the medical record throughout transplant as per standard of care for data extraction after Day +100

Phoenix Children's Hospital

Resident Physician

Antineoplastic Agents

Anti-Infective Agents

Analgesics

Etoposide

Cytarabine

Mitoxantrone

Etoposide phosphate

Idarubicin

Enzyme Inhibitors

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

I. Chemotherapy Induction-1: Cytarabine + idarubicin Induction-2: High dose (HD) cytarabine + mitoxantrone Consolidation-1: Cytarabine + idarubicin Consolidation-2: HD cytarabine + etoposide Consolidation-3: HD cytarabine + mitoxantrone Consolidation-4: HD cytarabine + etoposide

II. Allogeneic hematopoietic stem cell transplantation (HSCT) Favorable prognosis group: chemotherapy only Intermediate prognosis group: chemotherapy or HSCT with reduced intensity conditioning Poor prognosis group: HSCT with myeloablative conditioning

Hematopoietic stem cell transplantation

Keon Hee Yoo, MD, PhD

Hoon Kook, MD, PhD

Keon Hee, MD, PhD

Bin Cho, MD, PhD

The purpose of this study is to optimize therapy according to the known risk factors and treatment response in pediatric acute myeloid leukemia (AML)

I. Risk group assessment Favorable prognosis group: Low risk features + Good response

Intermediate prognosis group:

1. Low risk features + Delayed response-1
2. Standard risk features + Good response
3. Standard risk features + Delayed response-1

Poor prognosis group:

1. Any high risk features irrespective of treatment response
2. Any delayed response-2 irrespective of risk features
3. Any refractory state irrespective of risk features
4. Any early relapse

II. Chemotherapy Induction-1: Cytarabine + idarubicin Induction-2: High dose (HD) cytarabine + mitoxantrone Consolidation-1: Cytarabine + idarubicin Consolidation-2: HD cytarabine + etoposide Consolidation-3: HD cytarabine + mitoxantrone Consolidation-4: HD cytarabine + etoposide

III. Allogeneic hematopoietic stem cell transplantation (HSCT) Favorable prognosis group: chemotherapy only Intermediate prognosis group: chemotherapy or HSCT with reduced intensity conditioning Poor prognosis group: HSCT with myeloablative conditioning

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Home or Away From Home - Descriptive Interviews (Aim 2)	NCT02794207	Pediatric Acute...		8 Years - 22 Years	Children's Hospital of Philadelphia
Home Away From Home - Quality of Life Surveys	NCT02777021	Pediatric Acute...		-	Children's Hospital of Philadelphia
A Randomized Phase IV Control Trial of Single High Dose Oral Vitamin D3 in Pediatric Patients Undergoing HSCT	NCT03176849	Vitamin D Defic... Stem Cell Trans... Pediatric Cance... Blood Disorder Pediatric Acute... Pediatric Acute... Myelodysplastic... Sickle Cell Ane... Aplastic Anemia Thalassemia in ...	Vitamin D3 Standard Vitami...	1 Year - 25 Years	Phoenix Children's Hospital
Optimal Treatment Strategy Based on for Pediatric AML	NCT02848183	Pediatric Acute...	Cytarabine Idarubicin Mitoxantrone Etoposide Hematopoietic s...	- 18 Years	Samsung Medical Center
A Randomized Phase IV Control Trial of Single High Dose Oral Vitamin D3 in Pediatric Patients Undergoing HSCT	NCT03176849	Vitamin D Defic... Stem Cell Trans... Pediatric Cance... Blood Disorder Pediatric Acute... Pediatric Acute... Myelodysplastic... Sickle Cell Ane... Aplastic Anemia Thalassemia in ...	Vitamin D3 Standard Vitami...	1 Year - 25 Years	Phoenix Children's Hospital

Spots Global Cancer Trial Database for pediatric acute myeloid leukemia