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Phase II Study of Histone-deacetylase Inhibitor ITF2357 in Refractory/Relapsed Lymphocytic Leukemia

This study has been terminated.
(protocol needs complete restructuring in order to make it feasible and to complete the enrollment of 23 patients)
Information provided by (Responsible Party):
Italfarmaco Identifier:
First received: November 14, 2008
Last updated: May 23, 2013
Last verified: February 2012

This is an open label, un-controlled, phase II, pilot clinical trial testing ITF2357 in a population of CLL patients relapsed after or refractory to conventional chemotherapy or relapsed after autologus bone marrow transplantation.

Patient will receive ITF 2357 orally at the dose of 100 mg x 2/die for three months with subsequent dose modifications if requested by the patient's conditions.

Primary objective: To determine overall response-rate, complete response (CR) or partial response (PR) Secondary objectives: To assess the safety and tolerability of ITF2357; to assess total rate of responders (complete + partial responders); to determine the 6 months progression free survival; to determine the effects of the drug on haematological parameters.

Condition Intervention Phase
Chronic Lymphocytic Leukemia Drug: ITF2357 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open Label, Uncontrolled, Pilot, Phase II Study of Histone-deacetylase Inhibitor ITF2357 Administered Orally to Subjects With Chronic Lymphocytic Leukemia (CLL) Refractory/Relapsed After Conventional Chemotherapy or Relapsed After Autologous Bone Marrow Transplantation

Resource links provided by NLM:

Further study details as provided by Italfarmaco:

Primary Outcome Measures:
  • To determine overall response-rate, complete response (CR) or partial response (PR) to ITF2357 given at 100 mg x 2/die for up to three months [ Time Frame: 13 weeks ]

Secondary Outcome Measures:
  • To assess the safety and tolerability of ITF2357; to assess the rate of total responders (complete+partial responders); to determine the 6 months progression free survival; to determine the effects of the drug on haematological. parameters. [ Time Frame: 13 weeks ]

Enrollment: 3
Study Start Date: February 2008
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ITF2357 Drug: ITF2357
Histone-Deacetylase Inhibitor

Detailed Description:

CLL is the most frequent type of leukemia in the western world and affects mainly elderly individuals, although about one third of patients are less than 60 years of age at diagnosis.

CLL is a heterogeneous disease characterised by a surprisingly diverse clinical course with patients that may have an overall survival time ranging from months to decades.

CLL accounts for approximately 7000 new cases and 4500 deaths per year in the US.

Chemotherapeutic treatment of CLL is largely ineffective and despite new emerging therapies, CLL still remains an incurable disease.

ITF 2357 is a novel and proprietary molecule synthesized by Italfarmaco S.p.A. Research Laboratories, provided with an established and powerful HDAC-inhibitory activity (see below for further details). It is being developend for a range of possible clinical applications both in oncohaematological conditions and in chronic inflammatory diseases. The former application is consistent with the well known antitumor pharmacological properties of HDAC-inhibitors as a family (i.e. cell-cycle arrest, pro-apoptotic and cell-differentiating effects); the latter application (chronic inflammation) is based of the demonstrated anticytokine effect of ITF 2357.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Confirmed diagnosis of CLL according to the NCI Working Group criteria.
  • Male and female patients of age >18 and ≤75 years
  • Patients relapsed/refractory within 1 month after conventional chemotherapy (>1 polychemotherapy regimen) or relapsed within 3 months after autologous bone marrow transplantation
  • ECOG performance score of ≤2
  • Limphocytes ≥10.0x10^9/L and platelets >75.0x10^9/L after recovery from a previous therapy
  • Percentage of CD19+/CD5+ leukemic cells >50%
  • Adequate cardiac, pulmonary and renal function, as defined by LVEF >45%, FEV >50% and creatinine ≤1.5 ULN or creatinine clearance ≥50ml/min
  • Serum bilirubine <1.5xULN, AST and ALT <2.5xULN
  • Serum potassium, phosphorus, total calcium, magnesium >LLN
  • Normal values for FT4 and TSH (patients may be on thyroid hormone replacement)
  • Negative test for beta-HCG for women in fertile age
  • Documentation of written informed consent to participate in the trial
  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria:

  • Patients with Autoimmune haemolytic anaemia, Autoimmune Thrombocytopenic Purpura and Fischer Evans Syndrome.
  • Patients with other autoimmune diseases.
  • Patients with a marked baseline prolongation of QTc interval (e.g. repeated demonstration of a QTc interval >450 ms).
  • Patients with history of additional risk factors for torsade de pointes (e.g. hearth failure, family history of Long QT Syndrome)
  • The use of concomitant medications with potential risk of torsade de pointes and/or that can prolong QTc interval
  • Prior treatment with an HDAC inhibitor.
  • Treatment with Rituximab or Alemtuzumab within 90 days prior to study therapy.
  • Patients HIV positive, patients with active EBV, HBV, HCV infection or liver cirrhosis
  • Patients with active uncontrolled viral or bacterial or mycotic infection.
  • Major surgeries within 4 weeks from study start or not fully recovered from any previous surgical procedure.
  • Presence of any medical or psychiatric condition which may limit full compliance with the study or increase the risk associated with study participation or study drug administration.
  • Patients in treatment with corticosteroids within 1 month before study start
  • Significant cardiovascular disease (i.e., uncontrolled arrhythmias, unstable angina), or a major thromboembolic event (myocardial infarction, stroke, transient ischemic attack, pulmonary embolism, or non-catheter-related deep-vein thrombosis) in the last 6 months.
  • Uncontrolled hypertension.
  • Malabsorption syndromes.
  • Breast feeding women
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00792831

Department of Internal Medicine and Public Health, University of Perugia
Perugia, Italy, 06074
Sponsors and Collaborators
Study Director: Massimo Martelli, MD Department of Internal Medicine and Public Health, University of Perugia
  More Information

Responsible Party: Italfarmaco Identifier: NCT00792831     History of Changes
Other Study ID Numbers: DSC/06/2357/21
Study First Received: November 14, 2008
Last Updated: May 23, 2013

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Givinostat hydrochloride
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on June 22, 2017