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

Chronic Myelomonocytic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01305200
• Other study ID #: ACCL1031
• Secondary ID: NCI-2011-02635CD
• Status: Completed
• Phase: Phase 3
• Start date: March 2011
• Est. completion date: June 30, 2015

Study information

• Verified date: November 2016
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 226
• Est. completion date: June 30, 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• 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
• Hypereosinophilic Syndrome
• Juvenile Myelomonocytic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Lymphoma
• Lymphoma, Non-Hodgkin
• Mucositis
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
• Myeloproliferative Disorders
• Neoplasm Metastasis
• Neuroblastoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia
• 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
• Rhabdomyosarcoma
• Secondary Acute Myeloid Leukemia
• Secondary Myelodysplastic Syndromes
• Stomatitis
• Syndrome
• Testicular Neoplasms
• Unspecified Childhood Solid Tumor, Protocol Specific
• Wilms Tumor

Intervention

Drug:
• supersaturated calcium phosphate rinse
Mouth rinse

Other:
• placebo
Mouth rinse
• questionnaire administration
Ancillary studies

Procedure:
• quality-of-life assessment
Ancillary studies

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Ancillary Validation Study of ChIMES		Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.
Primary	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	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.
Secondary	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
Secondary	Incidence of Parenteral Opioid Analgesic Use (Morphine Equivalents).	Opioid Administration = yes	Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.
Secondary	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.
Secondary	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.
Secondary	Incidence of Total Parenteral Nutrition (TPN) Administration.	Total Parenteral Nutrition = yes	Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.
Secondary	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.
Secondary	Incidence of Febrile Neutropenia	Fever and Neutropenia = yes	Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.
Secondary	Incidence of Invasive Bacterial Infections	Invasive Bacterial Infection = yes	Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.
Secondary	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

External Links

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