Phase II Non-Randomised Trial of Oral Chlorophyllin in Haemorrhagic Cystitis from Radiation Therapy (CLARITY Trial): Clinical and Quality-of-Life Outcomes with Exploratory Proteomics

Objectives Chronic Haemorrhagic Cystitis (cHC) affects 5–15% of patients after pelvic radiotherapy. Sodium-copper-chlorophyllin, a semi-synthetic chlorophyll derivative, has shown promise in preclinical models. The phase II CLARITY trial evaluated oral chlorophyllin for radiation-induced cHC. Methods This prospective, single-centre, single-arm phase II trial (NCT05348239) enrolled adults with grade 2–4 haematuria persisting ≥ 3 months after pelvic radiotherapy. Participants received chlorophyllin 750 mg orally daily for 12 weeks. The primary endpoint was objective response rate (ORR), including complete (CR) and partial responses (PR). Secondary endpoints were safety, quality of life [Bladder Cancer Index (urinary function, bother) and EORTC QLQ-C30 (global health, summary score)] and exploratory proteomics. Results Twenty-four patients were enrolled (cervical cancer 15, rectal 5, prostate 4). Baseline haematuria was CTCAE grade 2 in 6 (25%), grade 3 in 17 (71%), and grade 4 in 1 (4%) patient. In the per-protocol analysis, the ORR was 70.8% (17/24; 95% CI 65%–83%;) with 9 CR and 8 PR, with a median time to response of 67 days and median response duration of 10 months. Chlorophyllin was well tolerated with no discontinuations and no severe adverse events. Side effects included greenish discolouration of stools in 79% and nausea in 16% patients. Significant improvements were noted for urinary function and bother and EORTC QLQ-C30 global health and summary scores. Proteomics suggested modulation of complement, coagulation, inflammatory, oxidative stress, and repair pathways. Conclusions Oral chlorophyllin showed encouraging response in radiotherapy-related haemorrhagic cystitis with favourable tolerability and quality of life gains. These findings support randomised trials to confirm efficacy and durability. Funding: Department of Atomic Energy, Government of India