Clinical Trial: A Two-part Study to Assess the Safety and Preliminary Efficacy of Givinostat in Patients With Polycythemia Vera

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Two-part Study Top Assess the Safety and Preliminary Efficacy of Givinostat in Patients With JAK2V617F Positive Polycythemia Vera

Brief Summary:

This is a two-part, multicenter, open label, non-randomized, phase Ib/II study to assess the safety and tolerability, Maximum Tolerated Dose and preliminary efficacy of Givinostat in patients with JAK2V617F positive Polycythemia Vera. Part A is the dose finding part while Part B is assessing the preliminary efficacy. Patients will be enrolled either in Part A or Part B and transition from one part to the other is not allowed.

Eligible patients for this study will have a confirmed diagnosis of Polycythemia Vera according to the revised World Health Organization criteria. Only if the enrolment in Part A is slow (i.e. < 5 patients enrolled in 3 months), eligibility for this part of the study may be expanded to all patients with chronic myeloproliferative neoplasms.

Study therapy will be administered in 28 day cycles (4 weeks of treatment). Disease response will be evaluated according to the European LeukemiaNet criteria after 3 and 6 cycles (i.e. at weeks 12 and 24, respectively) of treatment with Givinostat for both parts of the study. All phlebotomies performed in the first 3 weeks of treatment will not be counted to assess the clinico-haematological response.

The study will last up to a maximum of 24 weeks of treatment. However, after completion of the trial, all patients achieving clinical benefit will be allowed to continue treatment with Givinostat (at the same dose and schedule) in a long-term study.

Safety will be monitored at each visit throughout the entire duration of the study. Treatment will be administered on an outpatient basis and patients will be followed regularly with physical and laboratory tests, as specified in the protocol; in case of hospitalization, the treatment will be continued or interrupted acco

Detailed Summary:

This is a two-part, multicenter, open label, non-randomized, phase Ib/II study to assess the safety and tolerability, MTD and preliminary efficacy of Givinostat in patients with JAK2V617F positive PV.

Part A is the dose escalation portion of the study and, once the MTD has been established, Part B will commence where the preliminary efficacy of Givinostat in PV patients will be established. Patients will be enrolled either in Part A or Part B and transition from one part to the other is not allowed. Only PV patients from Part A assigned to the dose selected for Part B (MTD) may be counted towards the efficacy assessment in Part B.

Eligible patients for this study will have a confirmed diagnosis of PV according to the revised WHO criteria and the JAK2V617F positivity. Only if the enrolment in Part A is slow (i.e. < 5 patients enrolled in 3 months), eligibility for this part of the study may be expanded to all patients with cMPN.

After providing informed written consent before undertaking any protocol-related procedure, a unique patient identification code (i.e. patient screening ID which will be a combination of his/her site ID, study part ID and patient screening number, e.g. IT01-A01) will be assigned to each patient and it will identify the patient within his/her enrolment confirmation by Italfarmaco S.p.A. or its designee and never be reused in case of screening failure. After the enrolment confirmation and the assignation of the dose level before the first drug intake, a unique patient identification code (i.e. patient ID which will be a combination of patient screening number ID and dose level ID, e.g. IT01-A01-DL1) will be assigned to each patient and it will identify the patient throughout his/her participation in the study and never be reused in case of premature
Sponsor: Italfarmaco

Current Primary Outcome:

  • Part A: Maximum Tolerated Dose [ Time Frame: 168 days (i.e. 6 cycles) ]
    Determination of the Maximum Tolerated Dose of Givinostat based on cycle 1 Dose Limiting Toxicity's.
  • Part B: Preliminary efficacy after 3 cycles of treatment [ Time Frame: 84 days (i.e. 3 cycles) ]
    Overall response rate - i.e. Complete Response and Partial Response - of Givinostat at the Maximum Tolerated Dose after 3 cycles; the response will be evaluated according to the clinico-haematological European LeukemiaNet response criteria.
  • Part A: Safety and tolerability [ Time Frame: 168 days (i.e. 6 cycles) ]

    Safety and tolerability evaluated as following:

    • Number of patients experiencing adverse events;
    • Type, incidence, and severity of treatment-related adverse events.
  • Part B: Safety and tolerability after 3 cycles of treatment [ Time Frame: 84 days (i.e. 3 cycles) ]

    Safety and tolerability of Givinostat at the Maximum Tolerated Dose after 3 cycles evaluated as following:

    • Number of patients experiencing adverse events;
    • Type, incidence, and severity of treatment-related adverse events.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Part A: characterization of pharmacokinetic [ Time Frame: 84 and 168 days (i.e. clycles 3 and 6) ]
    Individual Givinostat concentrations tabulated by dose cohort along with descriptive statistics.
  • Part B: characterization of pharmacokinetic [ Time Frame: 168 days (i.e. 6 cycles) ]
    Individual Givinostat concentrations tabulated with descriptive statistics.
  • Part A: preliminary efficacy after 3 and 6 cycles of treatment [ Time Frame: 84 and 168 days (i.e. clycles 3 and 6) ]
    Overall response rate - i.e. Complete Response and Partial Response - of Givinostat at the Maximum Tolerated Dose after 3 and 6 cycles; the response will be evaluated according to the clinico-haematological European LeukemiaNet response criteria.
  • Part B: preliminary efficacy of Givinostat at the Maximum Tolerated Dose after 6 cycles. [ Time Frame: 168 days (i.e. 6 cycles) ]
    Overall response rate - i.e. Complete Response and Partial Response - of Givinostat at the Maximum Tolerated Dose after 6 cycles; the response will be evaluated according to the clinico-haematological European LeukemiaNet response criteria.
  • Part B: safety and tolerability after 6 cycles [ Time Frame: 168 days (i.e. 6 cycles) ]

    Safety and tolerability of Givinostat at the Maximum Tolerated Dose after 6 cycles evaluated as following:

    • Number of patients experiencing adverse events;
    • Type, incidence, and severity of treatment-related adverse events.


Original Secondary Outcome: Same as current

Information By: Italfarmaco

Dates:
Date Received: July 10, 2013
Date Started: October 2013
Date Completion: June 2018
Last Updated: March 1, 2017
Last Verified: March 2017