PB1981 RESULTS OBTAINED FROM CLINICAL TRIALS PHASE I/II IN HEMATOLOGICAL MALIGNANCIES. CLINICAL EXPERIENCE OF A SINGLE CENTER: HOSPITAL 12 OCTUBRE.
Authors: Cuéllar Pérez‐Ávila C. , Alonso Fernández R. , Ayala Díaz R. , De la Serna Torroba F.J. , Grande García C. , Rodríguez Izquierdo A. , Martínez Sánchez P. , Calbacho Robles M. , Sánchez Pina J.M. , Cedena Romero M.T. , Lahuerta Palacios J.J. , Martínez López J. 
Published: June 2019

Background:

Early phase clinical trials (phases I / II) represent a key element in the process of translation of knowledge, obtained in basic research, towards its application in clinical practice. Phase I studies are designed to evaluate the drug's safety and toxicity at different dose levels and determine drug pharmacokinetics and pharmacodynamics. In contrast, phase II trials focus on clinical effectiveness. In some cases, phase I studies are perceived as a high risk procedure for the achievement of an uncertain benefit.

Therefore, it seems appropriate to perform an analysis of the results obtained in early stage trials, in order to achieve a more objective risk/benefit assessment in this context.

Aims:

The main objective of the study was to analyze the safety and benefit of clinical trials in early stages in hematology. The results of overall survival (OS), progression free survival (PFS) and major toxicities between the phase I and phase II trials were compared.

Methods:

Data was extracted from medical histories of 262 patients with different hematological pathologies. These patients were admitted within one of the 66 phase I / II clinical trials opened between 2011 and 2018 at the Hospital 12 de Octubre. Data obtained was analyzed in terms of clinical response, toxicity and survival. We excluded 39 cases due to screening failure and 1 case due to withdrawal of the informed consent.

Results:

Considering the whole sample of patients, both in phase I (n = 77) and in phase II (n = 145), an overall response rate was verified (including complete and partial responses) in 66% of the patients. In 24% the disease remained stable and in 10% of cases it was refractory. The discontinuation rate of the studies in the whole series was 35.5%, mainly due to progression of the disease.

Overall survival (OS) was 34.6 months, while the progression‐free survival (PFS) was 31.6 months. There were significant differences in PFS between the group of patients in phase I (22.5 months) and phase II (35.7 months) (p = 0.004), but there were no differences in OS (p = 0.405). 33,7% and 32,4% of patients enrolled in phase I and phase II studies died, respectively. The main cause of death was progression.

Up to 39% of the patients included had some type of grade 3 or 4 toxicity, being hematological toxicity the most frequent(up to one third of the patients). In this regard, there were no significant differences between phase I and phase II trials, with 32.5% and 26.2% grade 3 or 4 toxicity, respectively.

Summary/Conclusion:

When comparing phase I and phase II trials, we found a higher PFS in phase II studies. This difference is probably due to the fact that part of the patients in phase I trials have received suboptimal doses of treatment, as the main objective of these studies is to warrant safety. However, when analyzing safety data, the differences between both groups in terms of grade 3 or higher toxicity are minimal and not statistically significant. In addition, there were no differences of OS between phase I and II trials.

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There are few reports in this regard that can be used as a reference. However, the results obtained in our center offer a hopeful outlook in the future of therapeutics in Hematology, confirming the existence of a significant clinical benefit in patients included in early phase clinical trials.