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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00792831
Recruitment Status : Terminated (protocol needs complete restructuring in order to make it feasible and to complete the enrollment of 23 patients)
First Posted : November 18, 2008
Last Update Posted : May 24, 2013
Information provided by (Responsible Party):

Brief Summary:

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 or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: ITF2357 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : February 2008
Actual Primary Completion Date : April 2009
Actual Study Completion Date : April 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: ITF2357 Drug: ITF2357
Histone-Deacetylase Inhibitor

Primary Outcome Measures :
  1. 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 :
  1. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00792831

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

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Responsible Party: Italfarmaco Identifier: NCT00792831    
Other Study ID Numbers: DSC/06/2357/21
First Posted: November 18, 2008    Key Record Dates
Last Update Posted: May 24, 2013
Last Verified: February 2012
Additional relevant MeSH terms:
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Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Histone Deacetylase Inhibitors
Givinostat hydrochloride
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action