phII Study of an HDAC Inhibitor in Very High-risk Relapsed/Refractory Hodgkin's Lymphoma Patients
This is a multi-center, open label, phase II study testing ITF2357 in a population of very high-risk relapsed/refractory Hodgkin's lymphoma patients.
The patients will receive 50 mg ITF2357 four times a day at 6-hour intervals in fed conditions for 28 consecutive days unless evidence of progressive disease, presence of unacceptable adverse events or patient's request to discontinue treatment occurs.
Decision regarding the continuation of ITF2357 will be made on:
- the basis of tumor reassessment upon completion of cycle defined as above and not later than 7 days and
- the occurred toxicity (if any). If complete response or partial response or stabilization of disease after first cycle, without concomitant relevant toxicities is observed, the treatment may continue as long as there is no evidence of progressive disease or appearance of unacceptable adverse events. In any case the treatment shall not exceed 84 days of drug intake overall (i.e. 12 weeks).
Treatment will be administered on an outpatient basis and patients will be followed regularly with physical and laboratory tests, as specified in the protocol; in case of hospitalization, the treatment will be continued or interrupted according to the Investigators' decision.
The study will accrue 23 patients evaluable for efficacy and the anticipated duration of the study is about 18 months.
|Hodgkin's Lymphoma||Drug: histone deacetylase inhibitor (ITF2357)||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase II Study of the Histone-deacetylase Inhibitor ITF2357 in Very High-risk Relapsed/Refractory Hodgkin's Lymphoma Patients|
- to evaluate the efficacy according to the International Working Group response criteria for Hodgkin's lymphomas [ Time Frame: every 28 days ]
|Study Start Date:||May 2007|
|Study Completion Date:||March 2009|
|Primary Completion Date:||March 2009 (Final data collection date for primary outcome measure)|
Drug: histone deacetylase inhibitor (ITF2357)
50 mg b.i.d. (or every 8 hours or every 6 hours), every day
Histone deacetylases (HDACs) are enzymes involved in the remodeling of chromatin, and have a key role in the epigenetic regulation of gene expression. In addition, the activity of non-histone proteins can be regulated through HDAC-mediated hypoacetylation. In recent years, inhibition of HDACs has emerged as a potential strategy to reverse aberrant epigenetic changes associated with cancer, and several classes of HDAC inhibitors have been found to have potent and specific anticancer activities in preclinical studies.
Hodgkin's lymphoma (HL) is a relatively uncommon lymphoma histotype, with an incidence in Italy of approximately 1700 new cases per year (approximately 12% of all lymphomas). Combination chemotherapy with or without radiotherapy cures approximately 70 percent of advanced-stage HL. Fifty percent of the failing patients can be salvaged by second line chemotherapy (mainly high-dose regimens), while the remaining patients eventually die by disease progression. The development of an effective salvage regimen for this refractory/resistant population represents a true unmet medical need.
The use in the latter patient subset of HDAC inhibitors, like ITF2357, is supported by several considerations. Namely: (1) a chemically related HDACi hydroxamate has shown activity in this clinical condition; (2) the drug markedly inhibits the production of several cytokines, and cytokine production in HL granuloma has a defined role in the pathogenesis of HL; (3) an effective treatment for refractory/relapsed HL is presently lacking; (4) ITF2357, up to 200 mg daily per os, has shown a favorable toxicity profile. All the above mentioned arguments represent a strong rationale prompting the use of ITF2357 in this patient population.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00496431
|Istituto Nazionale per lo studio e la cura dei Tumori|
|Milan, Italy, 20133|
|Principal Investigator:||Alessandro Massimo Gianni, MD||Istituto Nazionale per lo studio e la cura dei Tumori (Milan - Italy)|