Trial of the Histone-Deacetylase Inhibitor ITF2357 Followed by Mechlorethamine in Relapsed/Refractory Hodgkin's Lymphoma

• Status: Completed
• Trial end date: 2010-09-01
• Target enrollment: 0
• Participant gender: All

Summary

This study has the following objectives:

Primary Objective

• To evaluate the anti-lymphoma efficacy of daily oral doses of ITF2357 followed by intravenous Mechlorethamine administered to patients with refractory/relapsed Hodgkin's lymphoma.

Secondary Objective

• To evaluate the safety and tolerability of multiple courses of ITF2357 followed by Mechlorethamine in a population of chemotherapy pretreated patients.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Italfarmaco
• Treatments: Givinostat hydrochloride; Histone Deacetylase Inhibitors; Mechlorethamine

Criteria

Inclusion Criteria:

• Written Informed Consent;

• Age ≥18 years;

• Histologically confirmed diagnosis of Hodgkin's lymphoma;

• Subjects who have failed second-line or subsequent-line salvage chemo- radiotherapy regimens for whom no other treatment options of proven efficacy can be given;

• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements;

• 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;

• Subjects with at least one bi-dimensional lesion measurable by CT-scan or MRI, according to the Revised Response Criteria for Malignant Lymphoma of the International Working Group (J Clin Oncol, 25:579-586, 2007);

• 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;

• Life expectancy of >3 months;

• Subjects receiving intravenous Mechlorethamine (6 mg/sqm) as single agent at least 4 weeks before study entry;

• Willingness and capability to comply with the requirements of the study.

Exclusion Criteria:

• Active bacterial or mycotic infection requiring antimicrobial treatment

• Pregnancy or lactation

• Anticancer chemotherapy or radiotherapy during the study or within 4 weeks of study entry.

• A marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval > 450 ms, according to Bazett's correction formula - see appendix I for the formula)

• Use of concomitant medications that prolong the QT/QTc interval (see appendix H for full list)

• Clinically significant cardiovascular disease including:

• 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)

• 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 and JC virus.

• History of other diseases, metabolic dysfunctions, physical examination findings, or clinical laboratory findings 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