Chlorophyllin for Reducing Oral Mucositis in Total Body Irradiation Prior to Transplant

Официальное название

Chlorophyllin as an Adjunct for Reducing Oral Mucositis in Myeloablative Total Body Irradiation

Обзор

The goal of this phase II, single-arm interventional clinical trial is to evaluate whether oral sodium copper chlorophyllin (CHL) can reduce the frequency and severity of oral mucositis in patients aged 12-65 years undergoing myeloablative total body irradiation (TBI) as part of conditioning before their first allogeneic Hematopoietic Stem Cell Transplantation (HSCT). The main questions it aims to answer are: Does oral chlorophyllin reduce the incidence of Grade III and IV oral mucositis by day +28 after HSCT? Does oral chlorophyllin reduce the duration of severe oral mucositis and the need for total parenteral nutrition (TPN), opioid analgesics, and other treatment-related toxicities, while maintaining acceptable safety? Participants will: Receive oral sodium copper chlorophyllin 750 mg once daily (tablet or oral suspension) starting 48 hours before TBI conditioning and continuing until day +28 after HSCT. Undergo standard myeloablative TBI-based conditioning and allogeneic Hematopoietic Stem Cell Transplantation (HSCT) as part of routine clinical care. Have regular clinical assessments for oral mucositis, treatment-related toxicities, engraftment, and graft-versus-host disease (GVHD). Provide blood and saliva samples at predefined time points for cytokine and pharmacokinetic analyses.

Подробное описание

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.

Вмешательства

• Препарат Sodium Copper Chlorophyllin
  Sodium copper chlorophyllin (CHL) will be administered orally at a dose of 750 mg once daily (tablet or oral suspension) on an empty stomach, starting 48 hours before initiation of myeloablative total body irradiation (TBI) conditioning and continued until Day +28 after allogeneic hematopoietic stem cell transplantation (HSCT). The study drug is administered as an adjunct to standard TBI-based conditioning to evaluate its efficacy in reducing the incidence and severity of oral mucositis.

Первичные конечные точки

• Incidence of Grade III-IV Oral Mucositis [Срок оценки: From initiation of conditioning until Day +28 after HSCT.]

Вторичные конечные точки (9)

• Duration of Grade III-IV Oral Mucositis [Срок оценки: Day 0 to Day +28 after HSCT]
• Incidence of Total Parenteral Nutrition (TPN) Use [Срок оценки: Day 0 to Day +28 after HSCT]
• Duration of Total Parenteral Nutrition (TPN) [Срок оценки: Day 0 to Day +28 after HSCT]
• Incidence of Opioid Analgesic Use [Срок оценки: Day 0 to Day +28 after HSCT]
• Duration of Opioid Analgesic Use [Срок оценки: Day 0 to Day +28 after HSCT]
• Time to Neutrophil and Platelet Engraftment [Срок оценки: Up to Day +28 after HSCT]
• Incidence of Grade III-IV Diarrhea [Срок оценки: Day 0 to Day +28 after HSCT]
• Non-Relapse Mortality (NRM) [Срок оценки: 100 days after allogeneic HSCT]
• Cumulative Incidence of Grade III-IV Acute Graft-versus-Host Disease (GVHD) [Срок оценки: 100 days after allogeneic HSCT]

Критерии участия

Критерии включения

• Patients ≥12 and ≤65 years of age
• First allogeneic stem cell transplant
• Total body irradiation dose (fractionated) ≥8 Gy

Критерии исключения

• Known hypersensitivity or contraindications to sodium chlorophyllin (CHL)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Поддерживающая терапия

Центры проведения

Индия · 1 центр

• Advanced Centre for Treatment, Research and Education in Cancer — Navi Mumbai

Публикации

• Punatar S, Katti K, Rajamanickam D, Patil P, Dhakan C, Bagal B, Gokarn A, Bonda A, Nayak L, Gurjar M, Kannan S, Chiplunkar S, Gota V, Khattry N. Role of Curcumin in Reducing Toxicities Associated With Mucosal Injury Following Melphalan-Based Conditioning in Autologous Transplant Setting. Cell Transplant. 2022 Jan-Dec;31:9636897221086969. doi: 10.1177/09636897221086969. PMID 35435039
• Raber-Durlacher JE, von Bultzingslowen I, Logan RM, Bowen J, Al-Azri AR, Everaus H, Gerber E, Gomez JG, Pettersson BG, Soga Y, Spijkervet FK, Tissing WJ, Epstein JB, Elad S, Lalla RV; Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). Systematic review of cytokines and growth factors for the management of oral mu PMID 22987094
• Logan RM, Stringer AM, Bowen JM, Yeoh AS, Gibson RJ, Sonis ST, Keefe DM. The role of pro-inflammatory cytokines in cancer treatment-induced alimentary tract mucositis: pathobiology, animal models and cytotoxic drugs. Cancer Treat Rev. 2007 Aug;33(5):448-60. doi: 10.1016/j.ctrv.2007.03.001. Epub 2007 May 15. PMID 17507164
• CTRI clinical trial data of phase 1 study of chlorophyllin in healthy subjects - CTRI/2018/09/015576
• Kumar Gupta S, Gohil D, Dutta D, Panigrahi GC, Gupta P, Dalvi K, Khanka T, Yadav S, Kumar Kaushal R, Chichra A, Punatar S, Gokarn A, Mirgh S, Jindal N, Nayak L, Tembhare PR, Khizer Hasan S, Kumar Sandur S, Hingorani L, Khattry N, Gota V. Withaferin-A alleviates acute graft versus host disease without compromising graft versus leukemia effect. Int Immunopharmacol. 2023 Aug;121:110437. doi: 10.1016/ PMID 37311352
• Suryavanshi S, Sharma D, Checker R, Thoh M, Gota V, Sandur SK, Sainis KB. Amelioration of radiation-induced hematopoietic syndrome by an antioxidant chlorophyllin through increased stem cell activity and modulation of hematopoiesis. Free Radic Biol Med. 2015 Aug;85:56-70. doi: 10.1016/j.freeradbiomed.2015.04.007. Epub 2015 Apr 11. PMID 25872101
• Sharma D, Kumar SS, Sainis KB. Antiapoptotic and immunomodulatory effects of chlorophyllin. Mol Immunol. 2007 Jan;44(4):347-59. doi: 10.1016/j.molimm.2006.02.031. Epub 2006 Apr 17. PMID 16616780
• Kumar SS, Shankar B, Sainis KB. Effect of chlorophyllin against oxidative stress in splenic lymphocytes in vitro and in vivo. Biochim Biophys Acta. 2004 May 3;1672(2):100-11. doi: 10.1016/j.bbagen.2004.03.002. PMID 15110092

Идентификаторы

NCT: NCT07709195 · 901010

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗