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

NCT00792467 | Completed Phase 1 Results DMC

• 2 other identifiers: DSC/07/2357/312007-007091-41
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  OR rate among patients treated is defined according to the Revised Response Criteria for Malignant Lymphoma of the International Working Group. In medicine, a response rate is the percentage of patients whose cancer shrinks or disappears after treatment. The FDA definition of ORR is the proportion of patients with tumor size reduction of a predefined amount and for a minimum time period. The tumor objective response rate (ORR) is an important parameter to demonstrate the efficacy of a treatment in oncology. The ORR is valuable for clinical decision making in routine practice and a significant end-point for reporting the results of clinical trials.

  At each 21-day cycle for a maximum of 12 cycles

• Proportion of Responders (Complete -CR- or Partial PR-)

  Complete responder (CR) and partial responder (PR) among patients treated are defined according to the Revised Response Criteria for Malignant Lymphoma of the International Working Group. CR is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. PR is defined as regression of measurable disease and no new sites. The frequencies of patients achieving objective response (i.e. subjects whose best overall response was CR or PR) and the frequencies of patients who did not achieve an objective response (i.e.subjects whose best overall response was equal to stable disease - SD, progressive disease - PD - or not evaluable) in ITT and PP populations are reported. NED= no evidence of disease

  At each 21-day cycle for a maximum of 12 cycles

Secondary Outcomes (3)

• Progression-Free Survival (PFS)

  From the first day of the first cycle of treatment until objective tumor progression or death, whichever came first, assessed up to 450 days from the start of the first cycle of treatment

• Time To Response (TTR)

  From the first day of the first cycle until the date of achieving a response assessed up to 250 days from the start of the first cycle of treatment

• Response Duration (RD):

  From the first day of the first cycle of treatment until objective tumor progression or death, whichever came first, or last available tumor assessment (assessed up to 350 days from the start of the first cycle of treatment).

Study Arms (1)

ITF2357

EXPERIMENTAL

Patients received the following therapy cycle * ITF2357, 50 mg every 6 hours, per os, days 1 - 3; * Mechlorethamine, 6 mg/sqm, intravenously , day 4. Therapy was administered every 21 days as long as there was no evidence of progressive disease or unacceptable toxicity, but in any case for a maximum of 12 cycles. The mean number of complete treatment cycles received by patients was 5.25, with a minimum of 1 cycle and a maximum of 12 cycles.

Drug: ITF2357

Interventions

ITF2357 DRUG

ITF2357, supplied as hard gelatine capsules for oral administration at the strength of 50 mg each.

Also known as: Givinostat, histone deacetylase inhibitor

ITF2357

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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

Sponsors & Collaborators

• Italfarmaco: lead

Study Sites (1)

Istituto Nazionale per la Cura e lo Studio dei Tumori

Milan, 20133, Italy

Location

MeSH Terms

Conditions

Hodgkin Disease

Interventions

givinostat hydrochloride; givinostat; Histone Deacetylase Inhibitors

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Maurizio Caserini, MD
• Organization: Italfarmaco SpA

m.caserini@italfarmaco.com

+39 0264431

Study Officials

• Alessandro Massimo Gianni, MD

  Istituto Nazionale per la Cura e lo Studio dei Tumori, Milano, Italy

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2008
• First Posted: November 18, 2008
• Study Start: February 1, 2008
• Primary Completion: July 1, 2010
• Study Completion: September 1, 2010
• Last Updated: May 11, 2021
• Results First Posted: April 19, 2021

Record last verified: 2021-04

Locations

IT (1)