Phase I evaluation of radioimmunotherapy with 131I-CHT25 in patients with refractory IL2-receptor-expressing lymphomas


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Richard Begent2, Christopher McNamara2, Philip Ross1, James Ritchie1

1Cancer Research UK, London, UK, 2Royal Free Hospital, London, UK

Abstract

Background
Patients with relapsed or refractory Hodgkins or T-cell lymphoma continue to represent a population with an unmet clinical need. Radioimmunotherapy using iodine-131 radiolabelled CHT25 antibody directed against the interleukin-2 receptor is proposed as a novel treatment for this patient population.

Method
Fifteen patients were treated with 131I-CHT25 in an open label, non randomised, Phase 1 dose escalation study to determine maximum tolerated dose (MTD) and dose limiting toxicity (DLT). Dose levels administered ranged from 370 MBq/m2 to 2960 MBq/m2. Intra-patient dose escalation was permitted except in the last six patients, who were treated at either 1200 MBq/m2 or 1480 MBq/m2. Toxicity was assessed using NCI CTCAE v2.0 and response by modified Cheson criteria using CT / FDG-PET at 29 and 57 days post administration.

Results
One complete response and four partial responses were identified in 13 evaluable patients (39% overall response rate; ORR). Two patients not previously considered for high dose therapy due to chemo-resistant disease proceeded to transplant. Although MTD was not identified, 1200MBq/m2 was shown to be efficacious and is the recommended Phase II dose. The major toxicity identified was delayed myelo-suppression. No significant non-haematological toxicity was identified.

Conclusion
131I-CHT25 has demonstrated clinical activity in patients with refractory lymphoma at a radioactive dose level of 1200MBq/m2. DLTs identified were Grade 4 thrombocytopenia requiring transfusion and Grade 4 febrile neutropenia.

A Phase II study is planned to begin recruitment in early 2010 to further examine the efficacy of 131I-CHT25 in refractory HL patients by measuring ORR, 6-month progression free survival and overall survival at one year.

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