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

Summary

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 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.

Timeline

Start

2024-10-30

Primary completion

2027-03-05

Completion

2027-03-05

Publications

• Results 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.
• Results 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 mucositis in cancer patients. Support Care Cancer. 2013 Jan;21(1):343-55. doi: 10.1007/s00520-012-1594-5. Epub 2012 Sep 18.
• Results 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.
• Results CTRI clinical trial data of phase 1 study of chlorophyllin in healthy subjects - CTRI/2018/09/015576
• Results 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/j.intimp.2023.110437. Epub 2023 Jun 11.
• Results 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.
• Results 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.
• Results 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.
• Results US Patent. Chlorophyllin drug insert
• Results Brizel DM, Wasserman TH, Henke M, Strnad V, Rudat V, Monnier A, Eschwege F, Zhang J, Russell L, Oster W, Sauer R. Phase III randomized trial of amifostine as a radioprotector in head and neck cancer. J Clin Oncol. 2000 Oct 1;18(19):3339-45. doi: 10.1200/JCO.2000.18.19.3339.
• Results Rades D, Fehlauer F, Bajrovic A, Mahlmann B, Richter E, Alberti W. Serious adverse effects of amifostine during radiotherapy in head and neck cancer patients. Radiother Oncol. 2004 Mar;70(3):261-4. doi: 10.1016/j.radonc.2003.10.005.
• Results King M, Joseph S, Albert A, Thomas TV, Nittala MR, Woods WC, Vijayakumar S, Packianathan S. Use of Amifostine for Cytoprotection during Radiation Therapy: A Review. Oncology. 2020;98(2):61-80. doi: 10.1159/000502979. Epub 2019 Dec 17.
• Results Hadid T, Al-Katib A, Binongo J, Berteotti GM, Fazal S, Rossetti JM, Lister J. Palifermin Compared to Supersaturated Calcium Phosphate Rinse in Prevention of Severe Oral Mucositis after Stem Cell Transplantation in Patients Receiving Radiotherapy-Based Myeloablative Conditioning. Hemato. 2023; 4(1):58-67. https://doi.org/10.3390/hemato4010006
• Results Papas AS, Clark RE, Martuscelli G, O'Loughlin KT, Johansen E, Miller KB. A prospective, randomized trial for the prevention of mucositis in patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant. 2003 Apr;31(8):705-12. doi: 10.1038/sj.bmt.1703870.
• Results Spielberger R, Stiff P, Bensinger W, Gentile T, Weisdorf D, Kewalramani T, Shea T, Yanovich S, Hansen K, Noga S, McCarty J, LeMaistre CF, Sung EC, Blazar BR, Elhardt D, Chen MG, Emmanouilides C. Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med. 2004 Dec 16;351(25):2590-8. doi: 10.1056/NEJMoa040125.
• Results Nooka AK, Johnson HR, Kaufman JL, Flowers CR, Langston A, Steuer C, Graiser M, Ali Z, Shah NN, Rangaraju S, Nickleach D, Gao J, Lonial S, Waller EK. Pharmacoeconomic analysis of palifermin to prevent mucositis among patients undergoing autologous hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014 Jun;20(6):852-857. doi: 10.1016/j.bbmt.2014.02.025. Epub 2014 Mar 6.
• Results Pearlman R, Hanna R, Burmeister J, Abrams J, Dominello M. Adverse Effects of Total Body Irradiation: A Two-Decade, Single Institution Analysis. Adv Radiat Oncol. 2021 May 19;6(4):100723. doi: 10.1016/j.adro.2021.100723. eCollection 2021 Jul-Aug.
• Results Nakagaki M, Kennedy GA, Gavin NC, Clavarino A, Whitfield K. The incidence of severe oral mucositis in patients undergoing different conditioning regimens in haematopoietic stem cell transplantation. Support Care Cancer. 2022 Nov;30(11):9141-9149. doi: 10.1007/s00520-022-07328-4. Epub 2022 Aug 26.
• Results Langner S, Staber P, Schub N, Gramatzki M, Grothe W, Behre G, Rabitsch W, Urban C, Linkesch W, Neumeister P. Palifermin reduces incidence and severity of oral mucositis in allogeneic stem-cell transplant recipients. Bone Marrow Transplant. 2008 Aug;42(4):275-9. doi: 10.1038/bmt.2008.157. Epub 2008 May 26.
• Results Maria OM, Eliopoulos N, Muanza T. Radiation-Induced Oral Mucositis. Front Oncol. 2017 May 22;7:89. doi: 10.3389/fonc.2017.00089. eCollection 2017.
• Results Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M, Sandmaier B. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2009 Mar;15(3):367-9. doi: 10.1016/j.bbmt.2008.12.497.
• Results Gupta T, Kannan S, Dantkale V, Laskar S. Cyclophosphamide plus total body irradiation compared with busulfan plus cyclophosphamide as a conditioning regimen prior to hematopoietic stem cell transplantation in patients with leukemia: a systematic review and meta-analysis. Hematol Oncol Stem Cell Ther. 2011;4(1):17-29. doi: 10.5144/1658-3876.2011.17.
• Results Rehman MEU, Chattaraj A, Mahboob A, Ijaz Z, Franco D, Farhan M, Dharma K, Mumtaz H, Saeed S, Basit J, Aslam MM, Iftikhar A, Faraz F, Anwer F. Total Body Irradiation Versus Chemotherapy Conditioning in Pediatric Acute Lymphoblastic Leukemia Patients Undergoing Hematopoietic Stem Cell Transplant: A Systematic Review and Meta-Analysis. Clin Lymphoma Myeloma Leuk. 2023 Apr;23(4):249-258. doi: 10.1016/j.clml.2023.01.004. Epub 2023 Jan 14.
• Results Peters C, Dalle JH, Locatelli F, Poetschger U, Sedlacek P, Buechner J, Shaw PJ, Staciuk R, Ifversen M, Pichler H, Vettenranta K, Svec P, Aleinikova O, Stein J, Gungor T, Toporski J, Truong TH, Diaz-de-Heredia C, Bierings M, Ariffin H, Essa M, Burkhardt B, Schultz K, Meisel R, Lankester A, Ansari M, Schrappe M; IBFM Study Group;; von Stackelberg A; IntReALL Study Group; Balduzzi A; I-BFM SCT Study Group; Corbacioglu S; EBMT Paediatric Diseases Working Party; Bader P. Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study. J Clin Oncol. 2021 Feb 1;39(4):295-307. doi: 10.1200/JCO.20.02529. Epub 2020 Dec 17.
• Results Hartman AR, Williams SF, Dillon JJ. Survival, disease-free survival and adverse effects of conditioning for allogeneic bone marrow transplantation with busulfan/cyclophosphamide vs total body irradiation: a meta-analysis. Bone Marrow Transplant. 1998 Sep;22(5):439-43. doi: 10.1038/sj.bmt.1701334.
• Results Wolden SL, Rabinovitch RA, Bittner NH, Galvin JM, Giap HB, Schomberg PJ, Rosenthal SA; American College of Radiology; American Society for Radiation Oncology. American College of Radiology (ACR) and American Society for Radiation Oncology (ASTRO) practice guideline for the performance of total body irradiation (TBI). Am J Clin Oncol. 2013 Feb;36(1):97-101. doi: 10.1097/COC.0b013e31826e0528.
• Results Gyurkocza B, Sandmaier BM. Conditioning regimens for hematopoietic cell transplantation: one size does not fit all. Blood. 2014 Jul 17;124(3):344-53. doi: 10.1182/blood-2014-02-514778. Epub 2014 Jun 9.
• Results Thomas ED, Epstein RB. Bone marrow transplantation in acute leukemia. Cancer Res. 1965 Oct;25(9):1521-4. No abstract available.
• Results ODELL TT Jr, TAUSCHE FG, LINDSLEY DL, OWEN RD. The homotransplantation of functional erythropoietic elements in the rat following total-body irradiation. Ann N Y Acad Sci. 1957 Mar 22;64(5):811-23; discussion, 823-5. doi: 10.1111/j.1749-6632.1957.tb52475.x. No abstract available.

Drugs

Indications