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Phase II Study of the Histone-deacetylase Inhibitor ITF2357 in Very High-risk Relapsed/Refractory Hodgkin's Lymphoma Patients

Phase 1/Phase 2
18 Years
Not Enrolling
Hodgkin's Lymphoma

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Trial Information

Phase II Study of the Histone-deacetylase Inhibitor ITF2357 in Very High-risk Relapsed/Refractory Hodgkin's Lymphoma Patients

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.

Inclusion Criteria:

Signed Informed Consent Form; Age ≥ 18 years; History of histologically confirmed
Hodgkin's lymphoma Subjects are eligible for this trial if (1) they have failed at least 1
cycle of chemotherapy, with or without radiotherapy, and if (2) they are considered
incurable by the referring physician, and would be treated with second-line or
subsequent-line salvage regimens, mainly with palliative intent; Clinical laboratory
values ANC > 1500/µL; Platelet count > 75000/µL Hemoglobin > 9 g/dL (may not be transfused
or treated with erythropoietin to maintain or exceed this level) Total bilirubin < 1.6
mg/dL; AST or ALT < 2.5 times the upper limit of normal Serum creatinine < 2.0 mg/dL or
creatinine clearance > 50 mL/min Serum Potassium and Magnesium within normal limits;
Measurable disease (according to the International Working Group response criteria for
HL); ECOG performance status of 0 or 1; Use of an effective means of contraception for
women of childbearing potential and men with partners of childbearing potential (use per
institutional standard); Life expectancy of > 3 months;; At least 4 weeks since last
treatment for HL Willingness and capability to comply with the requirements of the study;

Exclusion Criteria:

Active bacterial or mycotic infection requiring antimicrobial treatment on Day 1;
Pregnancy or lactation; A marked baseline prolongation of QT/QTc interval (e.g. repeated
demonstration of a QTc interval > 450 ms, according to Bazett's correction formula); The
use of concomitant medications that prolong the QT/QTc interval;

Clinically significant cardiovascular disease e.g.:

Uncontrolled hypertension, myocardial infarction, unstable angina New York Heart
Association (NYHA) Grade II or greater congestive heart failure History of any cardiac
arrhythmia requiring medication (irrespective of its severity) Grade II or greater
peripheral vascular disease A history of additional risk factors for TdP (e.g., heart
failure, hypokalemia, family history of Long QT Syndrome); Positive blood test for HIV,
HBV and HCV; Identification of viral DNA by quantitative PCR for EBV (Ebstein Barr virus),
JC virus, CMV (Cytomegalovirus) and Herpes Zoster; History of other disease, metabolic
dysfunction, physical examination finding, or clinical laboratory finding giving
reasonable suspicion of a disease or condition that contraindicates use of an
investigational drug or that might affect interpretation of the results of the study or
render the subject at high risk from treatment complications;

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

to evaluate the efficacy according to the International Working Group response criteria for Hodgkin's lymphomas

Outcome Time Frame:

every 28 days

Safety Issue:


Principal Investigator

Alessandro Massimo Gianni, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Istituto Nazionale per lo studio e la cura dei Tumori (Milan - Italy)


Italy: Ministry of Health

Study ID:




Start Date:

May 2007

Completion Date:

March 2009

Related Keywords:

  • Hodgkin's Lymphoma
  • Hodgkin Disease
  • Lymphoma