Oral Mucositis
Conditions
Keywords
Oral Mucositis, Stomatitis, Myeloablative
Brief summary
Patients receiving high-dose chemotherapy/conditioning prior to stem cell transplantation (SCT) are at high risk for developing painful lesions in the oral cavity, known as oral mucositis (OM). In this high risk adult population, the study objectives are to investigate the efficacy and tolerability of Gelclair® (GEL; an FDA cleared medical device indicated for the management of painful oral lesions) and ideal timing of initiation of therapy (at the time of conditioning or after mild OM is diagnosed) for the management of oral mucositis (OM), relative to a commercially available compounded mouth wash (First® Mouthwash BLM Magic Mouth Wash; MMW) initiated after mild OM is diagnosed. The study may be adapted based on an interim analysis and recommendations of the interim data review committee.
Detailed description
Adult patients at high risk for developing OM receiving one of the following myeloablative (MA) pre-transplant conditioning regimens prior to allogeneic transplant along with methotrexate (MTX) as part of graft vs. host disease (GVHD) prophylaxis meeting all other eligibility criteria will be enrolled: * FluBu based regimens: either fludarabine: 30 mg/m\^2 x 4 days and busulfan 0.8 mg/kg IV q6h x 4 days; both given daily starting at day -4 OR fludarabine: 40 mg/m\^2 and busulfan: 3.2 mg/kg both given daily on days -6 through -3. * Bu/Cy: busulfan, 0.8 mg/kg IV q6h x 4 days (-7 through -4); cyclophosphamide: 60 mg/kg IV once on days -3 and -2 * Cy/TBI: Cyclophosphamide, 60 mg/kg IV given twice between days -3 and -1 and TBI fractionated (generally over 3 days) for a total of 12Gy GVHD Prophylaxis: • Regimens including methotrexate (MTX; 15 mg/m\^2 planned to be given on days 1, 3, 6 and 11); addition of other agents given along with MTX (e.g., tacrolimus, sirolimus) is acceptable. Duration of treatment: * Arm 1: GEL treatment a minimum of 4x/day initiated from 1st day of conditioning through OM resolution (G0), up to a maximum of 20d. * Arms 2 (GEL) and 3 (MMW): Treatment a minimum of 4x/day initiated when G1 or G2 OM diagnosed during observation period (through Day +14 relative to stem cell infusion) through OM resolution (G0), up to a maximum of 20d.
Interventions
DEVICEGelclair
Polyvinylpyrrolidone (PVP) and Sodium Hyaluronate-Containing Oral Gel
COMBINATION_PRODUCTFirst® Mouthwash BLM
Viscous Lidocaine, Diphenhydramine, and Aluminum-magnesium Hydroxide/Simethicone Antacid Suspension Mouthwash
Sponsors
PharPoint Research, Inc.
Midatech Pharma US Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Outcomes Assessor)
Masking description
OM grading via the WHO oral toxicity grading scale will be performed by the trained blinded evaluator at least 3X/week (e.g., M, W and F), with ≤ 48h (±24h) in between each assessment.
Intervention model description
The initial design is a prospective, randomized, single-blind (evaluator), parallel, three arm, controlled clinical study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Be age ≥ 18 years old. * Have Karnofsky performance status score ≥ 70. * Be scheduled to receive one of 3 myeloablative conditioning regimens (defined in population) followed by allogeneic SCT for hematological malignancy. * Have anticipated in-patient status for 14 to 20 days from the time of transplant. * Be willing and capable of swishing/gargling oral gel/solution as required per protocol. * Be willing and capable of completing the assessments and adhering to protocol requirements. * Be willing and able to provide written informed consent. To be randomized to begin treatment, subjects randomized to Arms 2 or 3 must also meet the following criterion: -Be diagnosed with G1 or G2 OM via WHO OM scale during observation period from conditioning to Day +14.
Exclusion criteria
* Subjects receiving pre-transplant conditioning/GVHD prophylaxis regimens other than those defined, herein. * Use of topical or systemic agents/treatments for OM within 2 weeks of treatment day 1. * Evidence of uncontrolled infection (oral/oropharyngeal or systemic), including oral herpes or unexplained febrile illness (≥ 99.5F /37.5C) requiring systemic anti-infectives, within 7d of treatment Day 1. * Subjects with active oral lesions or other mouth/throat soreness within 7d of study randomization. * Any other criteria, in the opinion of the investigator that would make the subject unsuitable for study participation. For subjects randomized to Treatment Arms 2 or 3 during observation period: -OM ≥ G3 diagnosed prior to initiating randomized treatment during observation period (conditioning through Day +14; i.e., missed treatment window).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence/occurrence of any grade Oral Mucositis | Initial study period (initiation of conditioning through day +14 post-transplant) | Incidence/develop of any grade of OM as assessed via WHO OM grading scale (Grades possible: 1-4) |
| Area under the curve in mouth and throat soreness (MTS) | While OM ongoing during study period (initiation of conditioning through day +28 post-transplant) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Opiate and other background pain medication use | While OM ongoing during study period (initiation of conditioning through day +28 post-transplant) | — |
| Duration of any grade OM | Study period (initiation of conditioning through day +28 post-transplant) | WHO Grades 1-4 |
| Severity of OM | Study period (initiation of conditioning through day +28 post-transplant) | WHO Grades 1-4 |
| Time to onset of any grade OM | Initial study period (initiation of conditioning through day +14 post-transplant) | WHO Grades 1-4 |
| Incidence of severe OM | Study period (initiation of conditioning through day +28 post-transplant) | WHO Grades 3-4 |
| Time to onset of severe OM | Study period (initiation of conditioning through day +28 post-transplant) | WHO Grades 3-4 |
| Duration of severe OM | Study period (initiation of conditioning through day +28 post-transplant) | WHO Grades 3-4 |
| Magnitude of OM-related pain control | While OM ongoing during study period (initiation of conditioning through day +28 post-transplant) | Based on subject grading of mouth and throat soreness (VAS 0 (no pain) to 10 (max pain possible)) prior to each randomized/rescue OM treatment. |
| Duration of pain control | While OM ongoing during study period (initiation of conditioning through day +28 post-transplant) | Based on time at a given mouth and throat soreness level and/or need for rescue treatment to control mouth and throat soreness. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Treatment Compliance with randomized OM treatment | Study period (initiation of conditioning through day +28 post-transplant) | Assessed by determining the number of randomized treatments actually taken relative to the number of treatments required (i.e., treatment compliance) |
| Use of rescue treatments other than randomized agent for managing OM | While OM ongoing during study period (initiation of conditioning through day +28 post-transplant) | — |
| Incidence of treatment-emergent xerostomia ≥ G2 | Study period (initiation of conditioning through day +28 post-transplant) | — |
| Duration of treatment-emergent xerostomia ≥ G2 | Study period (initiation of conditioning through day +28 post-transplant) | — |
| Use of treatments/medications to manage xerostomia | Study period (initiation of conditioning through day +28 post-transplant) | — |
| Duration of use for treatments/medications to manage xerostomia | Study period (initiation of conditioning through day +28 post-transplant) | — |
| Impact of OM on activities of daily living | Study period (initiation of conditioning through day +28 post-transplant) | Via validated oral mucositis daily questionnaire (OMDQ) |
| Diarrhea associated with OM | Study period (initiation of conditioning through day +28 post-transplant) | Via validated oral mucositis daily questionnaire (OMDQ) |
| Exploratory Safety/Tolerability of GEL and MMW | Study period (initiation of conditioning through day +28 post-transplant) | Assessed by treatment-emergent and related adverse events/serious adverse events/unanticipated adverse device effects and subject reported tolerability. |
| Weight change over study treatment period | Study period (initiation of conditioning through day +28 post-transplant) | — |
| Incidence of treatment-emergent infection | While OM ongoing during study period (initiation of conditioning through day +28 post-transplant) | e.g., bacteremia/febrile neutropenia, including oral infections (e.g., thrush). |
| Duration of treatment-emergent infections | While OM ongoing during study period (initiation of conditioning through day +28 post-transplant) | e.g., bacteremia/febrile neutropenia, including oral infections (e.g., thrush). |
| Use of anti-infectives for treatment-emergent infections | While OM ongoing during study period (initiation of conditioning through day +28 post-transplant) | Exploratory Endpoint |
| Duration of anti-infective use for treatment-emergent infections | While OM ongoing during study period (initiation of conditioning through day +28 post-transplant) | — |
| Dose level of anti-infectives for treatment-emergent infections | While OM ongoing during study period (initiation of conditioning through day +28 post-transplant) | — |
| Days of hospitalization post-SCT | Study period (initiation of conditioning through day +28 post-transplant) | — |
| Incidence of need for a modified diet | While OM ongoing during study period (initiation of conditioning through day +28 post-transplant) | For example, soft, liquid, TPN |
| Duration of need for a modified diet | While OM ongoing during study period (initiation of conditioning through day +28 post-transplant) | For example, soft, liquid, TPN |
Countries
United States
Outcome results
None listed