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

Phase 3

Completed

Conditions: Chronic Eosinophilic Leukemia
Chronic Neutrophilic Leukemia
Disseminated Neuroblastoma
Previously Treated Myelodysplastic Syndromes
Recurrent Childhood Acute Myeloid Leukemia
Recurrent Childhood Rhabdomyosarcoma
Recurrent Malignant Testicular Germ Cell Tumor
Recurrent/Refractory Childhood Hodgkin Lymphoma
Unspecified Childhood Solid Tumor, Protocol Specific
Childhood Acute Lymphoblastic Leukemia in Remission

Interventions: Other: placebo
Drug: supersaturated calcium phosphate rinse
Other: questionnaire administration
Procedure: quality-of-life assessment

Registration Number: NCT01305200

Lead Sponsor: Children's Oncology Group

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 226

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (placebo)	placebo	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.
Arm I (placebo)	questionnaire administration	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.
Arm I (placebo)	quality-of-life assessment	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.
Arm II (supersaturated calcium phosphate rinse)	supersaturated calcium phosphate rinse	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.
Arm II (supersaturated calcium phosphate rinse)	questionnaire administration	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.
Arm II (supersaturated calcium phosphate rinse)	quality-of-life assessment	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Incidence of Total Parenteral Nutrition (TPN) Administration.	Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.	Total Parenteral Nutrition = yes
Total Dose of Parenteral Opioid Analgesic Used (Morphine Equivalents).	Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.	Morphine equivalent dose in mg/kg/day
Incidence of Severe Oral Mucositis	Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.	Percentage of patients with Severe Oral Mucositis (WHO Grade 3 or 4) per arm.
Oral Mucositis Daily Questionnaire (OMDQ)	Day -1 (day prior to stem cell infusion) to Day 20 following transplantation	Area under the curve (AUC) of the Oral Mucositis Daily Questionnaire (OMDQ) subscales
Incidence of Parenteral Opioid Analgesic Use (Morphine Equivalents).	Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.	Opioid Administration = yes
Duration of Parenteral Opioid Analgesic Use (Morphine Equivalents).	Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.	Mean days of parenteral opioid analgesic use.
Duration of Total Parenteral Nutrition (TPN) Administration.	Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.	Mean days of total parenteral nutrition (TPN) administration.
Incidence of Febrile Neutropenia	Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.	Fever and Neutropenia = yes
Incidence of Invasive Bacterial Infections	Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.	Invasive Bacterial Infection = yes
Severity of Mucositis	Day -1 (day prior to stem cell infusion) to Day 20 following transplantation	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.

Trial Locations

Locations (35): Lurie Children's Hospital-Chicago
🇺🇸
Chicago, Illinois, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸
Pittsburgh, Pennsylvania, United States
Miami Children's Hospital
🇺🇸
Miami, Florida, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
University of Mississippi Medical Center
🇺🇸
Jackson, Mississippi, United States
Rady Children's Hospital - San Diego
🇺🇸
San Diego, California, United States
City of Hope
🇺🇸
Duarte, California, United States
University of Chicago
🇺🇸
Chicago, Illinois, United States
Floating Hospital for Children at Tufts Medical Center
🇺🇸
Boston, Massachusetts, United States
Children's Hospital and Research Center at Oakland
🇺🇸
Oakland, California, United States
Columbia University Medical Center
🇺🇸
New York, New York, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸
Atlanta, Georgia, United States
Riley Hospital for Children
🇺🇸
Indianapolis, Indiana, United States
Children's National Medical Center
🇺🇸
Washington, District of Columbia, United States
All Children's Hospital
🇺🇸
Saint Petersburg, Florida, United States
C S Mott Children's Hospital
🇺🇸
Ann Arbor, Michigan, United States
The Montreal Children's Hospital of the MUHC
🇨🇦
Montreal, Quebec, Canada
The Childrens Mercy Hospital
🇺🇸
Kansas City, Missouri, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Princess Margaret Hospital for Children
🇦🇺
Perth, Western Australia, Australia
Children's Oncology Group
🇺🇸
Arcadia, California, United States
University of California San Francisco Medical Center-Parnassus
🇺🇸
San Francisco, California, United States
Alfred I duPont Hospital for Children
🇺🇸
Wilmington, Delaware, United States
Kosair Children's Hospital
🇺🇸
Louisville, Kentucky, United States
Children's Hospital-Main Campus
🇺🇸
New Orleans, Louisiana, United States
University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Ny Cancer%
🇺🇸
Valhalla, New York, United States
Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
Hospital for Sick Children
🇨🇦
Toronto, Ontario, Canada
Royal Childrens Hospital
🇦🇺
Herston, Queensland, Australia
Midwest Children's Cancer Center
🇺🇸
Milwaukee, Wisconsin, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Children's Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States
Methodist Children's Hospital of South Texas
🇺🇸
San Antonio, Texas, United States
Montefiore Medical Center
🇺🇸
Bronx, New York, United States