Chlorophyllin for Reducing Oral Mucositis in Total Body Irradiation Prior to Transplant (ChROMME-TBI)

Total body irradiation (TBI)-based myeloablative conditioning is an established component of allogeneic hematopoietic stem cell transplantation (HSCT) for patients with Hematologic Malignancies, particularly acute leukemias. Although effective, TBI is associated with significant acute toxicities, among which oral mucositis is one of the most common and debilitating complications. Severe (Grade III-IV) oral mucositis can result in severe pain, inability to eat, increased opioid analgesic use, total parenteral nutrition (TPN), prolonged hospitalization, and increased risk of infection. Published studies have reported a 44-71% incidence of severe oral mucositis following TBI-based conditioning, while institutional data demonstrate an incidence of approximately 70%.

Currently, there is no widely available standard prophylactic therapy for preventing radiation-induced oral mucositis in patients undergoing TBI-based conditioning. Palifermin has shown benefit in selected transplant populations but has limited evidence in TBI recipients, is costly, and is not readily available in India. Therefore, there is a need for a safe, affordable, and effective preventive strategy.

Sodium copper chlorophyllin (CHL) is a phytopharmaceutical derived from chlorophyll with antioxidant, anti-inflammatory, immunomodulatory, and radioprotective properties. Preclinical studies have demonstrated that CHL scavenges radiation-induced free radicals, reduces radiation-related tissue injury, promotes hematopoietic recovery, and protects normal tissues without protecting malignant cells or compromising the graft-versus-leukemia effect. A completed Phase I clinical study in healthy volunteers demonstrated that oral CHL is safe and well tolerated.

This prospective, single-center, single-arm Phase II study will evaluate the efficacy and safety of oral CHL in reducing severe oral mucositis in patients undergoing myeloablative TBI prior to first allogeneic HSCT. Eligible participants aged 12-65 years will receive oral CHL 750 mg once daily (tablet or oral suspension) beginning 48 hours before initiation of TBI conditioning and continuing until day +28 after transplantation, in addition to standard conditioning and transplant care.

The primary endpoint is the incidence of Grade III-IV oral mucositis by day +28 following HSCT. Secondary endpoints include the duration of severe oral mucositis, incidence and duration of TPN and opioid analgesic use, incidence of Grade III-IV nausea, vomiting and diarrhea, time to neutrophil and platelet engraftment, cumulative incidence of acute graft-versus-host disease (GVHD) by day 100, and non-relapse mortality. Exploratory objectives include evaluation of inflammatory cytokine profiles and the pharmacokinetic profile of CHL.

The findings from this study will provide preliminary evidence regarding the effectiveness of chlorophyllin as an inexpensive and well-tolerated radioprotective agent for reducing oral mucositis in patients undergoing TBI-based conditioning for allogeneic HSCT and will inform the design of future randomized clinical trials.