Supersaturated Calcium Phosphate Rinse in Preventing Oral Mucositis in Young Patients Undergoing Autologous or Donor Stem Cell Transplant

Study Overview
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Brief Summary
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This randomized phase III trial is studying how well Caphosol rinse works in preventing mucositis in young patients undergoing autologous or donor stem cell transplant. Supersaturated calcium phosphate (Caphosol) rinse may be able to prevent mucositis, or mouth sores, in patients undergoing stem cell transplant.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine if topically administered supersaturated calcium phosphate (Caphosol), rinsed orally four times daily at the initiation of conditioning for hematopoietic stem cell transplantation (HSCT), reduces oral mucositis as demonstrated by a decrease in duration of severe oral mucositis (World Health Organization [WHO] grade 3 or 4), compared to placebo. SECONDARY OBJECTIVES: I. To determine whether Caphosol administration, when compared to placebo, reduces oral mucositis as demonstrated by a decrease in incidence of severe oral mucositis (WHO grade 3 or 4); severity of mucositis according to mouth pain categorical rating scale and Oral Mucositis Daily Questionnaire (OMDQ); incidence, total dose, and duration of parenteral opioid analgesic use (morphine equivalents); and incidence and duration of total parenteral nutrition (TPN) administration. II. To determine whether Caphosol administration, when compared to placebo, reduces the incidence of febrile neutropenia and invasive bacterial infections. III. To validate a new pediatric measure of oral mucositis termed the Children's International Mucositis Evaluation Scale (ChIMES). OUTLINE: This is a multicenter study. Patients are stratified according to conditioning regimen (total-body irradiation (TBI) or melphalan vs neither TBI nor melphalan) and hematopoietic stem cell transplantation (HSCT) (autologous vs allogeneic). Patients are randomized to 1 of 2 treatment arms. ARM I: Patients rinse and gargle with supersaturated calcium phosphate rinse over 1 minute four* times daily (QID) beginning on the first day (about day -7) of the conditioning regimen. ARM II: Patients rinse and gargle with placebo over 1 minute QID* beginning the first day (about day -7) of the conditioning regimen. NOTE: * Patients who reach WHO grade 3 or 4 mucositis have the option to request a total of 6 rinses daily. In both arms, treatment continues until day 20 post-transplantation OR until mucositis resolves to WHO grade =< 2 for two consecutive days OR on day 12 in patients who do not experience oral mucositis of at least WHO grade >= 1. Patients are assessed daily by trained healthcare professionals using the Oral Mucositis Daily Questionnaire (OMDQ), the Pain Rating Scale, the WHO Mucositis Scale, and the Children's International Mucositis Evaluation Scale (ChIMES) from day -1 and continuing until day 20. Patients are also observed for the incidence of total dose and duration of parenteral opioid analgesic use, duration of total parenteral nutrition (TPN) administration, febrile neutropenia, and invasive bacterial infections. After completion of study therapy, patients are followed up for 30 days.

Official Title
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A Randomized Double Blinded Trial of Topical Caphosol to Prevent Oral Mucositis in Children Undergoing Hematopoietic Stem Cell Transplantation

Conditions
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Childhood Acute Lymphoblastic Leukemia in Remission, Childhood Acute Myeloid Leukemia in Remission, Childhood Chronic Myelogenous Leukemia, Childhood Myelodysplastic Syndromes, Chronic Eosinophilic Leukemia, Chronic Myelomonocytic Leukemia, Chronic Neutrophilic Leukemia, de Novo Myelodysplastic Syndromes, Disseminated Neuroblastoma, Juvenile Myelomonocytic Leukemia, Mucositis, Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable, Previously Treated Childhood Rhabdomyosarcoma, Previously Treated Myelodysplastic Syndromes, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Recurrent Childhood Large Cell Lymphoma, Recurrent Childhood Lymphoblastic Lymphoma, Recurrent Childhood Rhabdomyosarcoma, Recurrent Childhood Small Noncleaved Cell Lymphoma, Recurrent Malignant Testicular Germ Cell Tumor, Recurrent Wilms Tumor and Other Childhood Kidney Tumors, Recurrent/Refractory Childhood Hodgkin Lymphoma, Relapsing Chronic Myelogenous Leukemia, Secondary Acute Myeloid Leukemia, Secondary Myelodysplastic Syndromes, Unspecified Childhood Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: supersaturated calcium phosphate rinse
* Other: placebo
* Other: questionnaire administration
* Procedure: quality-of-life assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing myeloablative autologous or allogeneic hematopoietic stem cell transplantation (HSCT) for any indication One or more of the following donor stem cell sources (autologous or allogeneic): Bone marrow Placental blood (umbilical cord blood) Cytokine-mobilized peripheral blood Patients eligible for allogeneic HSCT must have one of the following types of donor stem cells: Human leukocyte antigen (HLA)-matched sibling or parent Partially matched family donor (mismatched for a single HLA locus [Class I]) Fully matched unrelated marrow or peripheral blood stem cell donor HLA-matched or partially mismatched (at least 4 of 6 match) cord blood (Class I or II) Patients expecting to receive any type of myeloablative HSCT conditioning regimen are eligible No non-myeloablative or reduced-intensity conditioning regimens Eligible patients must not have received palifermin within 30 days prior to enrollment Eligible patients must not have received prior treatment with Caphosol Exclusion Criteria: Females of childbearing potential must have a negative pregnancy test; patients must agree to use an effective birth control method; lactating patients must agree not to nurse a child while on this trial

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Arm I (placebo)<br>Patients rinse and gargle with placebo over 1 minute QID beginning the first day (about day -7) of the conditioning regimen. Treatment continues until day 20 post-transplantation. | Other: placebo<br>* Mouth rinse<br>* Other names: PLCB;Other: questionnaire administration<br>* Ancillary studies<br>Procedure: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;|
| Experimental: Arm II (supersaturated calcium phosphate rinse)<br>Patients rinse and gargle with supersaturated calcium phosphate rinse over 1 minute QID beginning on the first day (about day -7) of the conditioning regimen. Treatment continues until day 20 post-transplantation. | Drug: supersaturated calcium phosphate rinse<br>* Mouth rinse<br>* Other names: Caphosol;Other: questionnaire administration<br>* Ancillary studies<br>Procedure: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Severe Oral Mucositis (WHO Grade 3 or 4) | Mean days of severe (WHO Grade 3 or 4) Mucositis. | Day -1 (day prior to stem cell infusion) to Day 20 following transplantation. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Severe Oral Mucositis | Percentage of patients with Severe Oral Mucositis (WHO Grade 3 or 4) per arm. | Day -1 (day prior to stem cell infusion) to Day 20 following transplantation. | 
| Oral Mucositis Daily Questionnaire (OMDQ) | Area under the curve (AUC) of the Oral Mucositis Daily Questionnaire (OMDQ) subscales | Day -1 (day prior to stem cell infusion) to Day 20 following transplantation | 
| Incidence of Parenteral Opioid Analgesic Use (Morphine Equivalents). | Opioid Administration = yes | Day -1 (day prior to stem cell infusion) to Day 20 following transplantation. | 
| Duration of Parenteral Opioid Analgesic Use (Morphine Equivalents). | Mean days of parenteral opioid analgesic use. | Day -1 (day prior to stem cell infusion) to Day 20 following transplantation. | 
| Total Dose of Parenteral Opioid Analgesic Used (Morphine Equivalents). | Morphine equivalent dose in mg/kg/day | Day -1 (day prior to stem cell infusion) to Day 20 following transplantation. | 
| Incidence of Total Parenteral Nutrition (TPN) Administration. | Total Parenteral Nutrition = yes | Day -1 (day prior to stem cell infusion) to Day 20 following transplantation. | 
| Duration of Total Parenteral Nutrition (TPN) Administration. | Mean days of total parenteral nutrition (TPN) administration. | Day -1 (day prior to stem cell infusion) to Day 20 following transplantation. | 
| Incidence of Febrile Neutropenia | Fever and Neutropenia = yes | Day -1 (day prior to stem cell infusion) to Day 20 following transplantation. | 
| Incidence of Invasive Bacterial Infections | Invasive Bacterial Infection = yes | Day -1 (day prior to stem cell infusion) to Day 20 following transplantation. | 
| Severity of Mucositis | Area Under the Curve of Severity of Mucositis. According to mouth pain categorical rating scale ranges 0-10 with higher scores reflecting more severe pain. | Day -1 (day prior to stem cell infusion) to Day 20 following transplantation |