Phase II Study of Histone-Deacetylase Inhibitor ITF2357 in Refractory/Relapsed Lymphocytic Leukemia - Full Text View

Sponsored by:	Italfarmaco
Information provided by:	Italfarmaco
ClinicalTrials.gov Identifier:	NCT00792831

Purpose

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 II

MedlinePlus related topics: Bone Marrow Transplantation Leukemia, Adult Acute Leukemia, Adult Chronic

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
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

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 ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	23
Study Start Date:	February 2008
Estimated Study Completion Date:	February 2009
Estimated Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Intervention Details:

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.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00792831

Contacts

Contact: Tiziano Oldoni, MD	+39 02 6443 2540	t.oldoni@italfarmaco.com
Contact: Carmine D'Urzo, MD	+39 02 64432584	c.durzo@italfarmaco.it

Locations

Italy
Department of Internal Medicine and Public Health, University of Perugia	Recruiting
Perugia, Italy, 06074
Contact: Massimo Martelli, MD +39 075 5781 mmartelli@mpg.it

Sponsors and Collaborators

Italfarmaco

Investigators

Study Director:

Massimo Martelli, MD

Department of Internal Medicine and Public Health, University of Perugia

More Information

Responsible Party:	Italfarmaco ( Tiziano Oldoni )
Study ID Numbers:	DSC/06/2357/21
Study First Received:	November 14, 2008
Last Updated:	November 17, 2008
ClinicalTrials.gov Identifier:	NCT00792831
Health Authority:	Italy: Ministry of Health

Study placed in the following topic categories:

Chronic lymphocytic leukemia
Lymphatic Diseases
Leukemia
Leukemia, Lymphoid
Immunoproliferative Disorders

Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-cell, chronic
Lymphoproliferative Disorders
Leukemia, B-Cell

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Immune System Diseases

ClinicalTrials.gov processed this record on January 15, 2009