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

NCT00792831 | Terminated Phase 2 DMC

• 2 other identifiers: DSC/06/2357/212006-005465-19
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Lymphocytic Leukemia

Keywords

CLL

Outcome Measures

Primary Outcomes (1)

• Rate of complete response (CR) or partial response (PR) to ITF2357 in all patients

  ITF2357 was given at 100 mg x 2/die for up to three months. A positive response was defined to be a patient experiencing a complete or partial remission. Complete remission (CR) Absence of lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms. Normal blood count: neutrophils ≥1.5x109/L, platelets \>100x109/L, lymphocytes ≤4.0x109/L, Hb \>11.0 g/dL (not supported by transfusion), BM biopsy: normal cellularity, lymphocytosis \<30%. Partial remission (PR) ≥50% reduction in blood lymphocytes and ≥50% reduction in lymphadenophaty and/or 50% reduction in hepatomegaly and/or splenomegaly. Neutrophils ≥1.5x109/L or 50% improvement over baseline, platelets \>100x109/L or 50% improvement over baseline, Hb \>11.0 g/dL or 50% improvement over baseline (not supported by transfusion) It was considered PR * CR with nodular infiltrates at bone marrow biopsy (RPn) * CR with persistent anemia and thrombocytopenia therapy-related

  13 weeks

Secondary Outcomes (3)

• Total rate of responders (complete+partial responders)

  13 weeks

• Six months progression free survival.

  Up to 6 months

• Number of subjects experiencing an adverse vents (AE), type, frequency, severity, timing and relatedness of AE

  Throughout the study till 90 days post treatment

Study Arms (1)

ITF2357

EXPERIMENTAL

ITF2357 was supplied as hard gelatine capsules for oral administration at the strength of 100 or 50 mg. Patients had to receive ITF2357 100 mg x 2/die at 12-hour intervals, in fed conditions, for three consecutive months.

Drug: ITF2357

Interventions

ITF2357 DRUG

Histone-Deacetylase Inhibitor

Also known as: Givinostat

ITF2357

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Lymphocytes ≥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 bilirubin \<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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Italfarmaco: lead

Study Sites (1)

Department of Internal Medicine and Public Health, University of Perugia

Perugia, 06074, Italy

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

givinostat hydrochloride; givinostat

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Massimo Martelli, MD

  Department of Internal Medicine and Public Health, University of Perugia

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2008
• First Posted: November 18, 2008
• Study Start: February 1, 2008
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: January 27, 2022

Record last verified: 2022-01

Locations

IT (1)