Clinical trial NCT01305200: Supersaturated Calcium Phosphate Rinse in Preventing Oral Mucositis in Young Patients Undergoing Autologous or Donor Stem Cell Transplant
Official title: A Randomized Double Blinded Trial of Topical Caphosol to Prevent Oral Mucositis in Children Undergoing Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: 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
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2011-02-28
Enrollment: 226
Sex: ALL
Minimum age (years): 4
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Duration of Severe Oral Mucositis (WHO Grade 3 or 4)
timeFrame: Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.
Secondary outcomes:
measure: Incidence of Severe Oral Mucositis
timeFrame: Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.
measure: Oral Mucositis Daily Questionnaire (OMDQ)
timeFrame: Day -1 (day prior to stem cell infusion) to Day 20 following transplantation
measure: Incidence of Parenteral Opioid Analgesic Use (Morphine Equivalents).
timeFrame: Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.
measure: Duration of Parenteral Opioid Analgesic Use (Morphine Equivalents).
timeFrame: Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.
measure: Total Dose of Parenteral Opioid Analgesic Used (Morphine Equivalents).
timeFrame: Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.
measure: Incidence of Total Parenteral Nutrition (TPN) Administration.
timeFrame: Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.
measure: Duration of Total Parenteral Nutrition (TPN) Administration.
timeFrame: Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.
measure: Incidence of Febrile Neutropenia
timeFrame: Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.
measure: Incidence of Invasive Bacterial Infections
timeFrame: Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.
measure: Severity of Mucositis
timeFrame: Day -1 (day prior to stem cell infusion) to Day 20 following transplantation
Other outcomes:
measure: Ancillary Validation Study of ChIMES
timeFrame: Day -1 (day prior to stem cell infusion) to Day 20 following transplantation.
Locations:
city: Arcadia
country: United States
facility: Children's Oncology Group
state: California
city: Duarte
country: United States
facility: City of Hope
state: California
city: Oakland
country: United States
facility: Children's Hospital and Research Center at Oakland
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital - San Diego
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center-Parnassus
state: California
city: Wilmington
country: United States
facility: Alfred I duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Miami
country: United States
facility: Miami Children's Hospital
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Egleston
state: Georgia
city: Chicago
country: United States
facility: Lurie Children's Hospital-Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Louisville
country: United States
facility: Kosair Children's Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Children's Hospital-Main Campus
state: Louisiana
city: Boston
country: United States
facility: Floating Hospital for Children at Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: C S Mott Children's Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: The Childrens Mercy Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Valhalla
country: United States
facility: Ny Cancer%
state: New York
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: San Antonio
country: United States
facility: Methodist Children's Hospital of South Texas
state: Texas
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center
state: Wisconsin
city: Herston
country: Australia
facility: Royal Childrens Hospital
state: Queensland
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: The Montreal Children's Hospital of the MUHC
state: Quebec
Study officials:
affiliation: Children's Oncology Group
name: Nathaniel Treister, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.