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.

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.

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).