Background and Rationale –

Bone marrow transplant (BMT) or Allogeneic hematopoietic stem cell transplant (HSCT) is an established curative option in patients with haematological malignancies. Total Body Irradiation (TBI) has been utilised as an important part of conditioning regimen prior to bone marrow transplantation. The administration of high-dose TBI is associated with immediate and delayed side effects. Commonly observed side effects during treatment include – vomiting sensation (nausea), vomiting, dryness of mouth, mucositis (ulcers in mouth), and diarrhoea. Oral mucositis (ulcers in the mouth) is considered to be the single worst outcome when irradiation is given prior to BMT. The possibility of getting severe oral mucositis is approximately 60-70%. Our prior experience shows 70% possibility of severe degree of oral mucositis with TBI. Since there is only one approved medicine – palifermin for treatment of radiation induced oral mucositis, prevention remains the most important key. While palifermin was beneficial, its benefit in subgroup of patients who received TBI-prior to BMT was not significant. Moreover, Palifermin is an injectable medication, which is not available in India, with significant additional costs resulting in financial burden on the patient. Other medicines (supersaturated calcium phosphate rinse, Amifostine) have not been well studied in BMT patients. Thus, there is no standard prophylaxis for the prevention of mucositis for patients receiving TBI prior to BMT. Hence, low-cost, non-invasive and safe options for prevention of severe mucositis are an unmet need.  

Sodium-copper-chlorophyllin (CHL) is a phytopharmaceutical drug obtained from green plant pigment, chlorophyll. Studies have shown that CHL has many good properties – stimulation of immunity, action against viruses and it also protects against side effects of radiation. A study done in BARC showed the radioprotective role of CHL after oral administration. Another study done in our institution in mice showed that CHL does not protect against blood cancer, and it also does not per se have any anti-cancer effect in BMT. In this study, we intend to evaluate the radioprotective efficacy of CHL in preventing severe mucositis in BMT patients.

Study treatment and plan

This will be a single-arm, phase 2 prospective study. Patients will be screened for inclusion in study prior to start of conditioning protocol. This study will enroll patients ≥12-65 years of age undergoing an allogeneic stem cell transplant who are scheduled to receive myeloablative doses of TBI (≥8Gy) for conditioning. CHL will be given at a dose of 750mg OD. Patients will be started on CHL from day-9 (two days prior to first dose of TBI), and continued till 28 days (day+28) post transplant.

Outcomes and statistics

Primary outcome of this study will be to study incidence of severe grade 3-4 oral mucositis till day+28 post-transplant. Secondary end-points of study will be to evaluate duration of grade 3-4 oral mucositis (in number of days), incidence and duration of pain killers (opioids), time to neutrophil and platelet engraftment (in days), incidence of vomiting, and diarrhea till day+28 post-transplant. We will also do special tests. These will be blood tests to look at the levels of medicine (CHL) in blood. Additionally, they will also look at levels of certain proteins
(called as cytokines) which increase and decrease in blood and saliva during mucositis.

Total 17 patients will be enrolled in two stages (minimax design). Favorable outcome in this study will correspond to “not developing grade 3-4 mucositis”. In first stage, 10 patients will be enrolled. Out of 10, if at-least 2 patients achieve a favorable outcome, study will proceed to stage 2. Additional 7 patients will be included in stage 2. Out of total 17, if ≥8 patients (out of 17) achieve a favorable outcome, study will be termed successful.