Gelclair at Conditioning or After Oral Mucositis Diagnosed vs. Magic Mouth Wash in Stem Cell Transplant Recipients

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Adaptive Design, Single-Blind, Randomized, Controlled Study Investigating Polyvinylpyrrolidone (PVP) and Sodium Hyaluronate-Containing Oral Gel (Gelclair®) in Comparison to Viscous Lidocaine, Diphenhydramine, and Aluminum-magnesium Hydroxide/Simethicone Antacid Suspension Mouthwash (Magic Mouthwash) for the Management of Oral Mucositis Associated With High Dose Chemotherapy and Methotrexate in Allogeneic Stem Cell Transplant Recipients

Conditions
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Oral Mucositis

Intervention / Treatment
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* Device: Gelclair
* Combination Product: First® Mouthwash BLM


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The initial design is a prospective, randomized, single-blind (evaluator), parallel, three arm, controlled clinical study.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1 (Gelclair at time of conditioning)<br>All subjects in study Arm 1 will receive GEL starting on the first day of conditioning. | Device: Gelclair<br>* Polyvinylpyrrolidone (PVP) and Sodium Hyaluronate-Containing Oral Gel<br>* Other names: Gelclair Bioadherent Oral Gel;|
| Active Comparator: Arm 2 (Gelclair when OM diagnosed)<br>Subjects in Arm 2 will be observed from initiation of conditioning to Day +14. If subjects develop G1 or G2 OM via WHO OM scale during this period, they will at that time be randomized to immediately receive GEL. | Device: Gelclair<br>* Polyvinylpyrrolidone (PVP) and Sodium Hyaluronate-Containing Oral Gel<br>* Other names: Gelclair Bioadherent Oral Gel;|
| Active Comparator: Arm 3 (MMW when OM diagnosed)<br>Subjects in Arm 2 will be observed from initiation of conditioning to Day +14. If subjects develop G1 or G2 OM via WHO OM scale during this period, they will at that time be randomized to immediately receive MMW. | Combination Product: First® Mouthwash BLM<br>* Viscous Lidocaine, Diphenhydramine, and Aluminum-magnesium Hydroxide/Simethicone Antacid Suspension Mouthwash<br>* Other names: Magic Mouth Wash;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence/occurrence of any grade Oral Mucositis | Incidence/develop of any grade of OM as assessed via WHO OM grading scale (Grades possible: 1-4) | Initial study period (initiation of conditioning through day +14 post-transplant) | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to onset of any grade OM | WHO Grades 1-4 | Initial study period (initiation of conditioning through day +14 post-transplant) | 
| Duration of any grade OM | WHO Grades 1-4 | Study period (initiation of conditioning through day +28 post-transplant) | 
| Severity of OM | WHO Grades 1-4 | Study period (initiation of conditioning through day +28 post-transplant) | 
| Incidence of severe OM | WHO Grades 3-4 | Study period (initiation of conditioning through day +28 post-transplant) | 
| Time to onset of severe OM | WHO Grades 3-4 | Study period (initiation of conditioning through day +28 post-transplant) | 
| Duration of severe OM | WHO Grades 3-4 | Study period (initiation of conditioning through day +28 post-transplant) | 
| Magnitude of OM-related pain control | 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. | While OM ongoing during study period (initiation of conditioning through day +28 post-transplant) | 
| Duration of pain control | Based on time at a given mouth and throat soreness level and/or need for rescue treatment to control mouth and throat soreness. | While OM ongoing during study period (initiation of conditioning through day +28 post-transplant) | 
| Opiate and other background pain medication use |  | While OM ongoing during study period (initiation of conditioning through day +28 post-transplant) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oral Mucositis, Stomatitis, Myeloablative