Phase II Clinical Trial of ITF2357 In Patients With Relapsed/Refractory Multiple Myeloma

NCT00792506 | Terminated Phase 2 DMC

• 2 other identifiers: DSC/07/2357/292008-001416-20
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Primary objective: To assess the safety of ITF 2357 administered once weekly at high pulse dose in patients with relapsing/refractory multiple myeloma. Secondary objectives:

1. 1.To evaluate the anti-tumour activity of ITF 2357 administered once weekly at high pulse dose in patients with advanced multiple myeloma, measured as decrease of M protein.
2. 2.To assess the therapeutic response to ITF3257 according to EBMT criteria.
3. 3.To determine pharmacokinetic profile of ITF 2357 administered following high pulse dose schedule.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Number of patients with relapsing/refractory multiple myeloma with TEAE, included serious AE

  Number of patients with TEAE, included serious AE, was assessed while receiving once weekly ITF2357 at high pulse dose.

  30 weeks

Secondary Outcomes (1)

• Decrease in M protein and clinical response rate (PR plus CR according to the European Group for Blood & Marrow Transplantation - EBMT- criteria).

  18 weeks

Study Arms (1)

ITF2357

EXPERIMENTAL

Eligible patients had to be treated with weekly single doses of ITF2357 according to the above mentioned treatment plan.

Drug: ITF2357

Interventions

ITF2357 DRUG

Treatment was to be administered on an inpatient basis from week 1 to week 13 and on an outpatient basis from week 14 to anticipated end of treatment (week 18). The patients had to be hospitalized on day 1 every week. The Investigator had to administer ITF 2357 in one single dose (two or three 200 mg capsules at one time) under his/her direct control.

Also known as: Histone-Deacetylase Inhibitor

ITF2357

Eligibility Criteria

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

You may qualify if:

• Established diagnosis of multiple myeloma according to International Myeloma Working Group diagnostic criteria
• Age ≥ 18 years
• Patient relapsed after at least 2 lines of conventional chemotherapy or high dose therapy with autologous or allogeneic stem cell support, and/or for whom no alternative treatments are available/suitable
• Increasing trend of monoclonal immunoglobulin or Bence-Jones proteinuria through the last 4 consecutive pre-screening measurements, already available in the patient history
• No chemotherapy or other investigational anticancer therapy for at least 3 weeks before the start of the study
• Full recovery from previous toxicities
• ECOG performance status 0-2
• Adequate bone marrow reserve: absolute neutrophil count ≥ 1000/ml; platelet count ≥ 90000/ml
• Adequate liver function: total bilirubin within normal institutional limits (PI center); AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional upper limit of normal (PI center)
• Adequate renal function: Creatinine ≤ 2.5 mg/dl or creatinine clearance ≥ 50 ml/min
• Either men or women, accepting to practice effective contraception during the entire study period unless documentation of infertility exists. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should immediately inform her treating physician; in this case ITF 2357 treatment will be promptly discontinued
• Able to understand and willing to sign the informed consent form.

You may not qualify if:

• Planned autologous or allogeneic bone marrow transplantation within 4 weeks of the initiation of ITF 2357 administration
• Concurrent use of medicines that would confound the interpretation of toxicities and anti-tumour activity of ITF 2357 (i.e. quinolones, macrolides, 5-HT3 antagonists except for palonosetron,)
• Clinically significant illness including, but not limited to, the following: active infection, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, cardiac arrhythmia (present or documented in the past, of any kind), any other condition (including laboratory abnormalities) that in the opinion of the Investigator places the patient to unacceptable risk for adverse outcome if he/she were to participate in the study
• Psychiatric illness/social situations that would limit compliance with study medication and protocol requirements
• Pregnant or lactating women
• Positive blood tests for HIV, HBV, HCV, active EBV and CMV
• Diseases related to active viral infections
• Patients with a marked baseline prolongation of QTc interval (e.g. repeated demonstration of a QTc interval \>440 ms for men and \>450 ms for women)
• Patients with history of additional risk factors for Torsade de Pointes (e.g. heart 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

Sponsors & Collaborators

• Italfarmaco: lead

Study Sites (1)

Presidio Ospedaliero R. Binaghi

Cagliari, 09127, Italy

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

givinostat hydrochloride; Histone Deacetylase Inhibitors

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Giorgio La Nasa, MD

  Presidio Ospedaliero R. Binaghi, Cagliari - Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: This was an open label
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2008
• First Posted: November 18, 2008
• Study Start: October 1, 2008
• Primary Completion: January 1, 2010
• Study Completion: July 1, 2010
• Last Updated: February 2, 2022

Record last verified: 2022-01

Locations

IT (1)