Oral Mucositis
Conditions
Keywords
Adolescents, Autologous Transplant, Chemotherapy, Children, Extra-oral Photobiomodulation Therapy, HCT, Hematopoietic Stem Cell Transplant, Low Level Light therapy, Oral Mucositis, PBM, Photobiomodulation Therapy
Brief summary
Oral mucositis is a significant and common toxicity experienced by patients who receive high-dose chemotherapy as a preparatory regimen for a hematopoietic cell transplant (HCT). Furthermore, oral mucositis has been reported as the single most debilitating side effect reported by patients undergoing HCT. The incidence of HCT mucositis among adults is estimated to range between 76% and 89%; however, comparisons are difficult due to variability in patient ages, treatments and criteria for scoring oral mucositis. The use of intra-oral photobiomodulation (PBM) therapy in adult patients after the development of oral mucositis is well documented and now included in the international mucositis guidelines, with limited evidence in pediatrics. This study will build evidence for the incorporation of extra-oral PBM therapy into daily nursing care of children and adolescents undergoing HCT. This intervention has potential in providing evidence for efficacy in the prevention and treatment of oral mucositis, the single most debilitating side effect reported by patients undergoing HCT. Primary Objective: * To evaluate feasibility and efficacy of photobiomodulation therapy (PBM) in reducing oral mucositis in children and adolescents at risk for grade 3 oral mucositis undergoing an allogeneic hematopoietic cell transplant (HCT). Secondary Objective: * To compare clinical manifestations associated with the development of oral mucositis between those treated with daily PBM and a matched control. Clinical factors to include: grade and duration or oral mucositis. Exploratory Objective: * To evaluate efficacy of photobiomodulation therapy in autologous patients at risk for grade 3 oral mucositis compared to matched control. * To evaluate utilization of play-based procedural preparation and treatment feasibility and parental satisfaction.
Detailed description
Children, adolescents and young adults admitted for an allogeneic HCT and those determined by the transplant team to be at risk for grade 3 oral mucositis will be eligible to receive PBM (34 x 660nm 10mW, 35 x 850nm 30mW: 1390 mW total power output) at an irradiance of 50mW/cm2. The PBM treatment will be administered via the THOR Model LX2M unit. After low light therapy consent, participants will be offered the opportunity to receive a play-based preparation. Those who elect to receive this child life preparation will be scheduled to meet with a trained certified child life specialist (CCL) prior to admission. The play-based preparation will incorporate age and developmentally appropriate explanations of the non-invasive procedure and will be adapted to each patient's psychosocial and cognitive developmental needs. Observation and treatment will begin the first day of conditioning (plus/minus 2 days). Those undergoing an allogeneic HCT will have treatment daily until Day +20 or engraftment (ANC ≥ 500 for two consecutive days). For those undergoing an autologous transplant, treatment will continue until engraftment (ANC ≥ 500 for two consecutive days) or until the patient is without mucositis for two consecutive days. The PBM will be administered extra-oral and intra-oral by trained research staff. Direct aim of the laser into the eye will be avoided and safety spectacles will be used with laser therapy. The safety spectacles will be prescribed according to age, with the adjustable Ibis Infant eye protection for patients less than 1 year of age and the adjustable kids laser safety googles for the young child. Patients, staff, and observers will wear laser safety glasses while PBM is in use. The parent may hold the device in place with assistance from the trained persons. After the initial LLLT treatment, a parent-reported satisfaction survey will be administered via paper questionnaire. The observation of oral mucositis will be conducted by non-study staff and conducted as clinical care by the nurse, advanced practice provider and/or physician. Each patient will have a daily oral assessment, with documentation of mucositis, grade, duration, pain assessment, days of nutrition support, use of narcotics, positive oral and blood cultures. All patients will receive the standard mouth care regimen prescribed for transplant patients. Each patient will be matched and compared to a previously treated patient. The comparison will be matched on primary disease, conditioning regimen, age and sex, with comparison of treatment variables of mucositis grade, duration, pain medications, days of nutritional support, blood and oral cultures, to day +20 or engraftment (depending upon which occurs first).
Interventions
DEVICEPhotobiomodulation Therapy (PBM)
The PBM will be delivered through application of the LED Cluster Probe externally to the right external buccal, left external buccal, mid face with mouth open and submandibular and left/right cervical. Patients who develop an oral lesion, intra-oral directed therapy will be administered with the dental light probe. For patients that can tolerate, an intraoral probe will deliver light directly onto the oral mucosa, this will then replace the mid face application with mouth open. Each laser application will be timed at 60 seconds.
OTHERPain and Oral Function Assessment
After the 6-minute laser/ treatment session the child and parent will complete the mucositis evaluation scale on paper or ipad which includes self-report oral function specific to ability to swallow, eat and drink, as well as the patient's self-reported need for medication specific to mouth pain.
OTHERParent-Reported Satisfaction Survey
A parent-reported satisfaction survey will be administered via paper questionnaire after the initial LLLT treatment. Parent satisfaction will be reported by parents on a 5-point Likert scale to questions adapted from a parent satisfaction survey used in a study regarding child life services in pediatric imaging.
Sponsors
Association of Pediatric Hematology Oncology Nurses
St. Jude Children's Research Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* No age limitation * To be admitted for an allogeneic hematopoietic cell transplant * All eligible autologous hematopoietic cell transplant, at risk for grade 3 mucositis per transplant service secondary to conditioning regimen or previous history of grade 3 mucositis * Dental exam prior to admission, as per preadmission criteria * Willingness of research participant to provide assent/consent and parent/ legal guardian/representative to give written informed consent.
Exclusion criteria
* Deemed by transplant team as unable to participate * Known sensitivity to light therapy * Inability or unwillingness of research participant or legal guardian/representative to give written informed consent. * CAR-Tcell Protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of Photo Biomodulation Therapy (PBM) in Reducing Oral Mucositis (OM) in Children and Adolescents at Risk for Grade 3 OM Undergoing an Allogeneic Hematopoietic Cell Transplant (HCT). | Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500) | Feasibility was assessed through the number of successful treatments (957) administered by the total number of attempted treatments (1023), providing the percentage of successful treatment administered. Daily treatment included 6 sites of PBM application, with application documented as receiving all 6 applications, in part treatment (at least one to five sites) or no treatment. A successful treatment was defined as successfully administered to 4 or more sites. Reasons for partial or no treatment was documented. Criteria for feasibility was 75%. |
| Efficacy of Photo Biomodulation Therapy (PBM) in Reducing Oral Mucositis (OM) in Children and Adolescents at Risk for Grade 3 OM Undergoing an Allogeneic Hematopoietic Cell Transplant (HCT). | Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500) | It was estimated from a retrospective review of HCT patients that 71% of participants undergoing a HCT developed grade 3 mucositis. With an estimated clinically meaningful effect size of 20% for PBM, the estimated percentage of PBM participant to develop grade 3 mucositis was set at 51%. An interim analysis was conducted after the enrollment of 40 participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess the Severity of Mucositis Grade 1-3 and Duration for Each Patient Treated With PBM Compared to Matched Controls | Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500) | Patients were ranked according to the severity of their mucositis (a weighted average of mucositis intensity (grade 1-3) by number of days duration) |
| Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control. | Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500) | Participants treated with PBM therapy were matched to a transplant control who was not treated with PBM. Patients were matched by age, sex, primary disease and transplant conditioning regimen. Total days of grade 1 OM were calculated between PBM treated and untreated |
| Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control | Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500) | Participants treated with PBM therapy were matched to a transplant control who was not treated with PBM. Patients were matched by age, sex, primary disease and transplant conditioning regimen. Total days of grade 1 OM were calculated between PBM treated and untreated. |
| Days of Hospitalization Between Groups | From the time of admission to discharge | Total days of hospitalization between the treated and control group |
Countries
United States
Participant flow
Recruitment details
43 patients were enrolled between February 2020 and May 2021 Historical Matched Controls were not enrolled on this study, therefore; they are not included in the protocol enrollment number.
Pre-assignment details
Forty-three (43) participants were enrolled with 3 participants withdrawing consent prior to the start of treatment. Historical Matched Controls: Information obtained through chart reviews; matched on age, sex, primary diagnosis, and conditioning regimens; mucositis grade collected; previously treated on Bone Marrow transplant studies and non-protocol treatment plans (NPTP): 12 on NPTP; 2 on NCT01807611; 9 on NCT03849651; 17 on NCT02790515; not treated with Photobiomodulation.
Participants by arm
| Arm | Count |
|---|---|
| Photobiomodulation Therapy (PBM) Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML) patients undergoing Allogeneic transplant treated with Photobiomodulation | 40 |
| Historical Matched Controls Historical control matched: Patients matched on age, sex, primary diagnosis, conditioning regimen who were previously treated on Bone Marrow transplant studies and non-protocol treatment plans. Information was obtained through chart reviews. | 40 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Historical Matched Controls | Photobiomodulation Therapy (PBM) | Total |
|---|---|---|---|
| Age, Continuous | 9.9 years STANDARD_DEVIATION 5.3 | 10.9 years STANDARD_DEVIATION 5.8 | 10.4 years STANDARD_DEVIATION 5.6 |
| Conditioning Regimen (choice=Chemotherapy) No | 0 Participants | 0 Participants | 0 Participants |
| Conditioning Regimen (choice=Chemotherapy) Yes | 40 Participants | 40 Participants | 80 Participants |
| Conditioning Regimen (choice=Radiation) No | 36 Participants | 36 Participants | 72 Participants |
| Conditioning Regimen (choice=Radiation) Yes | 4 Participants | 4 Participants | 8 Participants |
| Primary Disease Acute Lymphoblastic Leukemia (ALL) | 17 Participants | 12 Participants | 29 Participants |
| Primary Disease Acute Myeloid Leukemia (AML) | 23 Participants | 27 Participants | 50 Participants |
| Primary Disease Chronic Myeloid Leukemia (CML) | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized American Indian/Alaskan/White | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black | 8 Participants | 6 Participants | 14 Participants |
| Race/Ethnicity, Customized Not Otherwise Specified | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 26 Participants | 30 Participants | 56 Participants |
| Sex: Female, Male Female | 18 Participants | 19 Participants | 37 Participants |
| Sex: Female, Male Male | 22 Participants | 21 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 40 |
| other Total, other adverse events | 0 / 40 |
| serious Total, serious adverse events | 0 / 40 |
Outcome results
Primary
Efficacy of Photo Biomodulation Therapy (PBM) in Reducing Oral Mucositis (OM) in Children and Adolescents at Risk for Grade 3 OM Undergoing an Allogeneic Hematopoietic Cell Transplant (HCT).
It was estimated from a retrospective review of HCT patients that 71% of participants undergoing a HCT developed grade 3 mucositis. With an estimated clinically meaningful effect size of 20% for PBM, the estimated percentage of PBM participant to develop grade 3 mucositis was set at 51%. An interim analysis was conducted after the enrollment of 40 participants.
Time frame: Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500)
Population: All patients who received at least 75% of the attempted PMB(n=40).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Photobiomodulation Therapy (PBM) | Efficacy of Photo Biomodulation Therapy (PBM) in Reducing Oral Mucositis (OM) in Children and Adolescents at Risk for Grade 3 OM Undergoing an Allogeneic Hematopoietic Cell Transplant (HCT). | 8 Participants |
Comparison: The count, percentage and confidence interval were calculated for allogeneic HCT participants who receive PBM and developed Grade 3 mucositis. Whether the percentage of the prospective sample is significantly different from the estimated rate of 71% was accessed.95% CI: [0.091, 0.356]
Primary
Feasibility of Photo Biomodulation Therapy (PBM) in Reducing Oral Mucositis (OM) in Children and Adolescents at Risk for Grade 3 OM Undergoing an Allogeneic Hematopoietic Cell Transplant (HCT).
Feasibility was assessed through the number of successful treatments (957) administered by the total number of attempted treatments (1023), providing the percentage of successful treatment administered. Daily treatment included 6 sites of PBM application, with application documented as receiving all 6 applications, in part treatment (at least one to five sites) or no treatment. A successful treatment was defined as successfully administered to 4 or more sites. Reasons for partial or no treatment was documented. Criteria for feasibility was 75%.
Time frame: Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500)
Population: All PrOM study patients who received allogeneic transplant. Forty participants were treated daily for a total of 1023 patient encounters, during 66 patient encounters we were unable to treat 4 or more sites
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Photobiomodulation Therapy (PBM) | Feasibility of Photo Biomodulation Therapy (PBM) in Reducing Oral Mucositis (OM) in Children and Adolescents at Risk for Grade 3 OM Undergoing an Allogeneic Hematopoietic Cell Transplant (HCT). | 93 percentage of successful treatments |
Secondary
Assess the Severity of Mucositis Grade 1-3 and Duration for Each Patient Treated With PBM Compared to Matched Controls
Patients were ranked according to the severity of their mucositis (a weighted average of mucositis intensity (grade 1-3) by number of days duration)
Time frame: Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500)
Population: Within each grade of mucositis (1-3) participants and controls were ranked against each other by days of mucositis duration. Each participant and control had 3 rankings for the 3 mucositis grades. The weighted average for each participant and control was calculated. Within each group (participant vs. control) there was a ranking (1-35 with the lower score being more severe mucositis). Statistical analysis then compared the weighted average between the two groups.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Photobiomodulation Therapy (PBM) | Assess the Severity of Mucositis Grade 1-3 and Duration for Each Patient Treated With PBM Compared to Matched Controls | Grade 3 | 19 Days of mucositis within each grade |
| Photobiomodulation Therapy (PBM) | Assess the Severity of Mucositis Grade 1-3 and Duration for Each Patient Treated With PBM Compared to Matched Controls | Grade 1 | 143 Days of mucositis within each grade |
| Photobiomodulation Therapy (PBM) | Assess the Severity of Mucositis Grade 1-3 and Duration for Each Patient Treated With PBM Compared to Matched Controls | Grade 2 | 80 Days of mucositis within each grade |
| Historical Matched Controls | Assess the Severity of Mucositis Grade 1-3 and Duration for Each Patient Treated With PBM Compared to Matched Controls | Grade 2 | 178 Days of mucositis within each grade |
| Historical Matched Controls | Assess the Severity of Mucositis Grade 1-3 and Duration for Each Patient Treated With PBM Compared to Matched Controls | Grade 1 | 177 Days of mucositis within each grade |
| Historical Matched Controls | Assess the Severity of Mucositis Grade 1-3 and Duration for Each Patient Treated With PBM Compared to Matched Controls | Grade 3 | 46 Days of mucositis within each grade |
p-value: 0.03Wilcox Rank Sum
Secondary
Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control
Participants treated with PBM therapy were matched to a transplant control who was not treated with PBM. Patients were matched by age, sex, primary disease and transplant conditioning regimen. Total days of grade 2 OM were calculated between PBM treated and untreated.
Time frame: Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500)
Population: All patients in treatment and control group who developed grade 2 at various days, their duration of grade 2 data was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Photobiomodulation Therapy (PBM) | Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control | 2 Days | Standard Deviation 2.1 |
| Historical Matched Controls | Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control | 4.45 Days | Standard Deviation 4.99 |
| Overall | Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control | 3.23 Days | Standard Deviation 4 |
Secondary
Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control
Participants treated with PBM therapy were matched to a transplant control who was not treated with PBM. Patients were matched by age, sex, primary disease and transplant conditioning regimen. Total days of grade 1 OM were calculated between PBM treated and untreated.
Time frame: Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500)
Population: All patients in treatment and control group who developed grade 1 at various days, their duration of grade 1 data was used.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Photobiomodulation Therapy (PBM) | Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control | 3 Days |
| Historical Matched Controls | Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control | 4 Days |
| Overall | Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control | 4 Days |
p-value: 0.32Wilcoxon (Mann-Whitney)
Secondary
Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control
Participants treated with PBM therapy were matched to a transplant control who was not treated with PBM. Patients were matched by age, sex, primary disease and transplant conditioning regimen. Total days of grade 2 OM were calculated between PBM treated and untreated.
Time frame: Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500)
Population: All patients in treatment and control group who developed grade 2 at various days, their duration of grade 2 data was used.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Photobiomodulation Therapy (PBM) | Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control | 1.5 Days |
| Historical Matched Controls | Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control | 2.5 Days |
| Overall | Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control | 2 Days |
p-value: 0.002Wilcoxon (Mann-Whitney)
Secondary
Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control
Participants treated with PBM therapy were matched to a transplant control who was not treated with PBM. Patients were matched by age, sex, primary disease and transplant conditioning regimen. Total days of grade 3 OM were calculated between PBM treated and untreated.
Time frame: Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500)
Population: All patients in treatment and control group who developed grade 3 at various days, their duration of grade 3 data was used.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Photobiomodulation Therapy (PBM) | Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control | 0 Days |
| Historical Matched Controls | Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control | 0 Days |
| Overall | Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control | 0 Days |
p-value: 0.1Wilcoxon (Mann-Whitney)
Secondary
Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control.
Participants treated with PBM therapy were matched to a transplant control who was not treated with PBM. Patients were matched by age, sex, primary disease and transplant conditioning regimen. Total days of grade 3 OM were calculated between PBM treated and untreated.
Time frame: Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500)
Population: All patients in treatment and control group who developed grade 3 at various days, their duration of grade 3 data was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Photobiomodulation Therapy (PBM) | Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control. | 0.47 Days | Standard Deviation 1.15 |
| Historical Matched Controls | Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control. | 1.15 Days | Standard Deviation 2.18 |
| Overall | Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control. | 0.81 Days | Standard Deviation 1.77 |
Secondary
Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control.
Participants treated with PBM therapy were matched to a transplant control who was not treated with PBM. Patients were matched by age, sex, primary disease and transplant conditioning regimen. Total days of grade 1 OM were calculated between PBM treated and untreated
Time frame: Daily assessment from day 1 of conditioning to 20 days after transplant or engraftment (2 consecutive days of an Absolute Neutrophil Count (ANC)>500)
Population: All patients in treatment and control group who developed grade 1 at various days, their duration of grade 1 data was used.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Photobiomodulation Therapy (PBM) | Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control. | 3.58 Days | Standard Deviation 2.91 |
| Historical Matched Controls | Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control. | 4.43 Days | Standard Deviation 3.85 |
| Overall | Compare the Mucositis Grade and Duration Between Those Who Received PBM and Match Control. | 4 Days | Standard Deviation 3.42 |
Secondary
Days of Hospitalization Between Groups
Total days of hospitalization between the treated and control group
Time frame: From the time of admission to discharge
Population: All patients in treatment and control group during their hospitalization for BMT.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Photobiomodulation Therapy (PBM) | Days of Hospitalization Between Groups | 32 Days of hospitalization |
| Historical Matched Controls | Days of Hospitalization Between Groups | 35 Days of hospitalization |
p-value: 0.009Wilcoxon (Mann-Whitney)
Secondary
Days of Hospitalization Between Groups
Total days of hospitalization between the treated and control group
Time frame: From the time of admission to discharge
Population: All patients in treatment and control group during their hospitalization for Bone Marrow Transplant (BMT).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Photobiomodulation Therapy (PBM) | Days of Hospitalization Between Groups | 32.4 Days of hospitalization | Standard Deviation 6.4 |
| Historical Matched Controls | Days of Hospitalization Between Groups | 40.2 Days of hospitalization | Standard Deviation 15.7 |