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

Oral Mucositis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03490396
• Other study ID #: GEL-401
• Status: Terminated
• Phase: Phase 4
• Start date: May 15, 2018
• Est. completion date: November 15, 2019

Study information

• Verified date: November 2019
• Source: Midatech Pharma US Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 28
• Est. completion date: November 15, 2019
• Est. primary completion date: November 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Mucositis
• Oral Mucositis
• Stomatitis

Intervention

Device:
• Gelclair
Polyvinylpyrrolidone (PVP) and Sodium Hyaluronate-Containing Oral Gel

Combination Product:
• First® Mouthwash BLM
Viscous Lidocaine, Diphenhydramine, and Aluminum-magnesium Hydroxide/Simethicone Antacid Suspension Mouthwash

Locations

Country	Name	City	State
United States	Brigham & Women's Hospital/Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Midatech Pharma US Inc.	PharPoint Research, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Weight change over study treatment period		Study period (initiation of conditioning through day +28 post-transplant)
Other	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)
Other	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)
Other	Use of anti-infectives for treatment-emergent infections	Exploratory Endpoint	While OM ongoing during study period (initiation of conditioning through day +28 post-transplant)
Other	Duration of anti-infective use for treatment-emergent infections		While OM ongoing during study period (initiation of conditioning through day +28 post-transplant)
Other	Dose level of anti-infectives for treatment-emergent infections		While OM ongoing during study period (initiation of conditioning through day +28 post-transplant)
Other	Days of hospitalization post-SCT		Study period (initiation of conditioning through day +28 post-transplant)
Other	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)
Other	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)
Other	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)
Other	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)
Other	Incidence of treatment-emergent xerostomia = G2		Study period (initiation of conditioning through day +28 post-transplant)
Other	Duration of treatment-emergent xerostomia = G2		Study period (initiation of conditioning through day +28 post-transplant)
Other	Use of treatments/medications to manage xerostomia		Study period (initiation of conditioning through day +28 post-transplant)
Other	Duration of use for treatments/medications to manage xerostomia		Study period (initiation of conditioning through day +28 post-transplant)
Other	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)
Other	Diarrhea associated with OM	Via validated oral mucositis daily questionnaire (OMDQ)	Study period (initiation of conditioning through day +28 post-transplant)
Other	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)
Primary	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)
Primary	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	Time to onset of any grade OM	WHO Grades 1-4	Initial study period (initiation of conditioning through day +14 post-transplant)
Secondary	Duration of any grade OM	WHO Grades 1-4	Study period (initiation of conditioning through day +28 post-transplant)
Secondary	Severity of OM	WHO Grades 1-4	Study period (initiation of conditioning through day +28 post-transplant)
Secondary	Incidence of severe OM	WHO Grades 3-4	Study period (initiation of conditioning through day +28 post-transplant)
Secondary	Time to onset of severe OM	WHO Grades 3-4	Study period (initiation of conditioning through day +28 post-transplant)
Secondary	Duration of severe OM	WHO Grades 3-4	Study period (initiation of conditioning through day +28 post-transplant)
Secondary	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)
Secondary	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)
Secondary	Opiate and other background pain medication use		While OM ongoing during study period (initiation of conditioning through day +28 post-transplant)

External Links

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