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

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

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.

Study Overview

• Status: Completed
• Conditions: Unspecified Childhood Solid Tumor, Protocol Specific; Chronic Myelomonocytic Leukemia; Juvenile Myelomonocytic Leukemia; Secondary Acute Myeloid Leukemia; Childhood Acute Myeloid Leukemia in Remission; Mucositis; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes; Recurrent Childhood Rhabdomyosarcoma; Chronic Neutrophilic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Disseminated Neuroblastoma; Recurrent Wilms Tumor and Other Childhood Kidney Tumors; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Recurrent Malignant Testicular Germ Cell Tumor; Chronic Eosinophilic Leukemia
• Intervention / Treatment: Other: questionnaire administration; Procedure: quality-of-life assessment; Other: placebo; Drug: supersaturated calcium phosphate rinse

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.

• Study Type: Interventional
• Enrollment (Actual): 226
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Childrens Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6008
      • Princess Margaret Hospital for Children
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children
  • Quebec
    • Montreal, Quebec, Canada, H3H 1P3
      • The Montreal Children's Hospital of the MUHC
• United States
  • California
    • Arcadia, California, United States, 91006-3776
      • Children's Oncology Group
    • Duarte, California, United States, 91010
      • City of Hope
    • Oakland, California, United States, 94609-1809
      • Children's Hospital and Research Center at Oakland
    • San Diego, California, United States, 92123
      • Rady Children's Hospital - San Diego
    • San Francisco, California, United States, 94143
      • University of California San Francisco Medical Center-Parnassus
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Alfred I duPont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Miami, Florida, United States, 33155
      • Miami Children's Hospital
    • Saint Petersburg, Florida, United States, 33701
      • All Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta - Egleston
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60614
      • Lurie Children's Hospital-Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Kosair Children's Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70118
      • Children's Hospital-Main Campus
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02111
      • Floating Hospital for Children at Tufts Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • C S Mott Children's Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University Of Mississippi Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • The Childrens Mercy Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New York
    • Bronx, New York, United States, 10467-2490
      • Montefiore Medical Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Valhalla, New York, United States, 10595
      • Ny Cancer%
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • Texas
    • San Antonio, Texas, United States, 78229
      • Methodist Children's Hospital of South Texas
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Midwest Children's Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm I (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.	Other: questionnaire administration; Ancillary studies; Procedure: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment; Other: placebo; Mouth rinse; Other Names: PLCB
Experimental: Arm II (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.	Other: questionnaire administration; Ancillary studies; Procedure: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment; Drug: supersaturated calcium phosphate rinse; Mouth rinse; Other Names: Caphosol

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Time Frame
Ancillary Validation Study of ChIMES	Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Nathaniel Treister, MD, Children's Oncology Group

Publications and helpful links

General Publications

• Treister N, Nieder M, Baggott C, Olson E, Chen L, Dang H, Krailo M, August A, Sung L. Caphosol for prevention of oral mucositis in pediatric myeloablative haematopoietic cell transplantation. Br J Cancer. 2017 Jan 3;116(1):21-27. doi: 10.1038/bjc.2016.380. Epub 2016 Nov 22.

Helpful Links

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 30, 2015

Study Registration Dates

• First Submitted: February 25, 2011
• First Submitted That Met QC Criteria: February 25, 2011
• First Posted (Estimate): February 28, 2011

Study Record Updates

• Last Update Posted (Actual): September 17, 2019
• Last Update Submitted That Met QC Criteria: September 9, 2019
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Disease Attributes; Disease; Gonadal Disorders; Bone Marrow Diseases; Hematologic Diseases; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Genital Neoplasms, Male; Testicular Diseases; Genetic Diseases, Inborn; Gastroenteritis; Stomatognathic Diseases; Mouth Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Kidney Neoplasms; Neoplastic Processes; Neoplastic Syndromes, Hereditary; Neoplasms, Complex and Mixed; Precancerous Conditions; Leukocyte Disorders; Sarcoma; Neuroectodermal Tumors, Primitive; Eosinophilia; Neoplasms, Muscle Tissue; Neuroectodermal Tumors, Primitive, Peripheral; Myosarcoma; Lymphoma; Syndrome; Myelodysplastic Syndromes; Testicular Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasm Metastasis; Recurrence; Lymphoma, Non-Hodgkin; Preleukemia; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Hypereosinophilic Syndrome; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Mucositis; Neuroblastoma; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Rhabdomyosarcoma; Wilms Tumor; Stomatitis; Rhabdomyosarcoma, Embryonal; Leukemia, Neutrophilic, Chronic; Physiological Effects of Drugs; Calcium-Regulating Hormones and Agents; Calcium
• Other Study ID Numbers: ACCL1031 (Other Identifier: CTEP); U10CA095861 (U.S. NIH Grant/Contract); NCI-2011-02635 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CDR0000695718 (Other Identifier: Clinical Trials.gov); COG-ACCL1031 (Other Identifier: DCP)