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

• Status: Terminated
• Trial end date: 2009-04-01
• Target enrollment: 0
• Participant gender: All

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.

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

Details

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

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