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

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

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.

Study Overview

• Status: Terminated
• Conditions: Oral Mucositis
• Intervention / Treatment: Device: Gelclair; Combination product: First® Mouthwash BLM

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02120
      • Brigham & Women's Hospital/Dana-Farber Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 (Gelclair at time of conditioning); All subjects in study Arm 1 will receive GEL starting on the first day of conditioning.	Device: Gelclair; Polyvinylpyrrolidone (PVP) and Sodium Hyaluronate-Containing Oral Gel; Other Names: Gelclair Bioadherent Oral Gel
Active Comparator: Arm 2 (Gelclair when OM diagnosed); 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; Polyvinylpyrrolidone (PVP) and Sodium Hyaluronate-Containing Oral Gel; Other Names: Gelclair Bioadherent Oral Gel
Active Comparator: Arm 3 (MMW when OM diagnosed); 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; Viscous Lidocaine, Diphenhydramine, and Aluminum-magnesium Hydroxide/Simethicone Antacid Suspension Mouthwash; Other Names: Magic Mouth Wash

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight change over study treatment period		Study period (initiation of conditioning through day +28 post-transplant)
Incidence of treatment-emergent infection	e.g., bacteremia/febrile neutropenia, including oral infections (e.g., thrush).	While OM ongoing during study period (initiation of conditioning through day +28 post-transplant)
Duration of treatment-emergent infections	e.g., bacteremia/febrile neutropenia, including oral infections (e.g., thrush).	While OM ongoing during study period (initiation of conditioning through day +28 post-transplant)
Use of anti-infectives for treatment-emergent infections	Exploratory Endpoint	While OM ongoing during study period (initiation of conditioning through day +28 post-transplant)
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	For example, soft, liquid, TPN	While OM ongoing during study period (initiation of conditioning through day +28 post-transplant)
Duration of need for a modified diet	For example, soft, liquid, TPN	While OM ongoing during study period (initiation of conditioning through day +28 post-transplant)
Treatment Compliance with randomized OM treatment	Assessed by determining the number of randomized treatments actually taken relative to the number of treatments required (i.e., treatment compliance)	Study period (initiation of conditioning through day +28 post-transplant)
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	Via validated oral mucositis daily questionnaire (OMDQ)	Study period (initiation of conditioning through day +28 post-transplant)
Diarrhea associated with OM	Via validated oral mucositis daily questionnaire (OMDQ)	Study period (initiation of conditioning through day +28 post-transplant)
Exploratory Safety/Tolerability of GEL and MMW	Assessed by treatment-emergent and related adverse events/serious adverse events/unanticipated adverse device effects and subject reported tolerability.	Study period (initiation of conditioning through day +28 post-transplant)

Collaborators and Investigators

• Sponsor: Midatech Pharma US Inc.
• Collaborators: PharPoint Research, Inc.
• Investigators: Study Director: Mary Kay Delmedico, PhD, Midatech Pharma US Inc.

Publications and helpful links

Helpful Links

• Gelclair Website (Study Agent)
• Midatech Pharma US (Study Sponsor) Website
• Poster Describing Study and Rationale/New Analysis of Data for GEL vs. MMW

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2018
• Primary Completion (Actual): November 15, 2019
• Study Completion (Actual): November 15, 2019

Study Registration Dates

• First Submitted: March 14, 2018
• First Submitted That Met QC Criteria: March 30, 2018
• First Posted (Actual): April 6, 2018

Study Record Updates

• Last Update Posted (Actual): November 22, 2019
• Last Update Submitted That Met QC Criteria: November 20, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Stomatitis; Oral Mucositis; Myeloablative
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Stomatognathic Diseases; Mouth Diseases; Mucositis; Stomatitis; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Plasma Substitutes; Blood Substitutes; Viscosupplements; Povidone; Hyaluronic Acid
• Other Study ID Numbers: GEL-401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No